Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
</div>
 
</div>
−
{{#lst:Section editor transclusions|anhl}}
+
{{#lst:Section editor transclusions|nsclc}}
 +
''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Non-small cell lung cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Non-small cell lung cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
 +
<br>There are several related dedicated pages:
 +
*'''Histology-specific:'''
 +
**'''[[Non-small_cell_lung_cancer,_nonsquamous|NSCLC, Nonsquamous]]'''
 +
**'''[[Non-small_cell_lung_cancer,_squamous|NSCLC, Squamous]]'''
 +
*'''Biomarker-specific:'''
 +
**'''[[Non-small_cell_lung_cancer,_ALK-positive|NSCLC, ALK-positive]]'''
 +
**'''[[Non-small_cell_lung_cancer,_BRAF-mutated|NSCLC, BRAF-mutated]]'''
 +
**'''[[Non-small_cell_lung_cancer,_EGFR-mutated|NSCLC, EGFR-mutated]]'''
 +
**'''[[Non-small_cell_lung_cancer,_HER2-mutated|NSCLC, HER2-mutated]]'''
 +
**'''[[Non-small_cell_lung_cancer,_KRAS-mutated|NSCLC, KRAS-mutated]]'''
 +
**'''[[Non-small cell lung cancer, MET-mutated|NSCLC, MET-mutated]]'''
 +
**'''[[Non-small cell lung cancer, RET-positive|NSCLC, RET-positive]]'''
 +
**'''[[Non-small_cell_lung_cancer,_ROS1-positive|NSCLC, ROS1-positive]]'''
 +
*'''[[CNS carcinoma]]'''
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
|-
 
|-
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
|}
 
|}
−
'''''Note 1:''' Regimens specifically intended for HIV-related Burkitt lymphoma can be found on the [[HIV-associated_lymphoma|HIV-associated lymphoma]] page.''
 
−
'''''Note 2:''' The regimens on this page are primarily intended for the sporadic form of Burkitt lymphoma and some other high-grade B-cell lymphomas. In the future we plan to add regimens for the endemic form of Burkitt lymphoma.
 
−
For pediatric regimens, please visit the [[Non-Hodgkin lymphoma, pediatric|pediatric NHL page]].
 
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 
=Guidelines=
 
=Guidelines=
 +
==[https://www.asco.org/ ASCO]==
 +
*'''2022:''' Daly et al. [https://doi.org/10.1200/jco.21.02528 Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline]
 +
*'''2020:''' Schneider et al. [https://doi.org/10.1200/jco.19.02748 Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline]
 +
===Older===
 +
*'''2017:''' Hanna et al. [https://doi.org/10.1200/JCO.2017.74.6065 Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/28806116 PubMed]
 +
*'''2015:''' Masters et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019421/ Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update]
 +
*'''2009:''' Azzoli et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2793036/ American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer]
 +
==ASCO/CCO==
 +
===Current===
 +
*'''2021:''' Hanna et al. [https://doi.org/10.1200/jco.20.03570 Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update]
 +
*'''2020:''' Hanna et al. [https://doi.org/10.1200/jco.19.03022 Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update]
 +
*'''2017:''' Kris et al. [https://doi.org/10.1200/JCO.2017.72.4401 Adjuvant systemic therapy and adjuvant radiation therapy for stage I to IIIA completely resected non–small-cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario clinical practice guideline update] [https://pubmed.ncbi.nlm.nih.gov/28437162 PubMed]
 +
===Older===
 +
*'''2007:''' Pisters et al. [https://doi.org/10.1200/JCO.2007.14.1226 Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non small-cell lung cancer guideline] [https://pubmed.ncbi.nlm.nih.gov/17954710 PubMed]
 +
==[http://www.esmo.org/ ESMO]==
 +
*'''2018:''' Planchard et al. [https://doi.org/10.1093/annonc/mdy275 Metastatic Non-Small-Cell Lung Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 +
*'''2015:''' Eberhardt et al. [https://doi.org/10.1093/annonc/mdv187 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer]
 +
===Older===
 +
*'''2016:''' Novello et al. [https://doi.org/10.1093/annonc/mdw326 Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 +
*'''2014:''' Vansteenkiste et al. [https://doi.org/10.1093/annonc/mdu089 2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up]
 +
*'''2014:''' Besse et al. [https://doi.org/10.1093/annonc/mdu123 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease]
 +
*'''2014:''' Kerr et al. [https://doi.org/10.1093/annonc/mdu145 Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer]
 +
*'''2013:''' Vansteenkiste et al. [https://doi.org/10.1093/annonc/mdt241 Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 +
==KSMO/ESMO==
 +
*'''2020:''' Park et al. [https://doi.org/10.1016/j.annonc.2019.10.026 Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS]
 
==[https://www.nccn.org/ NCCN]==
 
==[https://www.nccn.org/ NCCN]==
−
*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
+
*[https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf NCCN Guidelines - Non-Small Cell Lung Cancer]
−
*[https://www.nccn.org/professionals/physician_gls/pdf/ped_b-cell.pdf NCCN Guidelines - Pediatric Aggressive Mature B-Cell Lymphomas]
+
=Neoadjuvant therapy=
−
=Untreated, pre-phase=
+
==Carboplatin & Paclitaxel (CP) {{#subobject:3a6h8q|Regimen=1}}==
−
==CVP {{#subobject:1a817a|Regimen=1}}==
+
CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
−
CVP: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 
−
<br>COP: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:865d9b|Variant=1}}===
+
===Regimen {{#subobject:1yg1q7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nivolumab|CP & Nivolumab]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29_.26_Nivolumab|CVb & Nivolumab]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Nivolumab|DC & Nivolumab]]
 +
| style="background-color:#d73027" |Inferior EFS
 +
|-
 +
|}
 +
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 or 200 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]]
 +
</div></div>
 +
===References===
 +
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
 +
==Carboplatin & Paclitaxel (CP) & Nivolumab {{#subobject:3a6hg7|Regimen=1}}==
 +
CP & Nivolumab: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, Nivolumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:59hhq7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|CVb]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29|DC]]
 +
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 31.6 vs 20.8 mo<br>(HR 0.63, 97.38% CI 0.43-0.91)<br><br>Superior pCR rate<br>24% vs 2.2%<br>(OR 13.94, 99% CI 3.49-55.75)
 +
|-
 +
|}
 +
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 or 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 or 200 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles'''
 +
====Immunotherapy====
 +
*[[Nivolumab (Opdivo)]] 360 mg IV once on day 1
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]]
 +
</div></div>
 +
===References===
 +
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
 +
==Cisplatin & Docetaxel (DC) {{#subobject:cab6b8|Regimen=1}}==
 +
DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 60-75/75 x 3 {{#subobject:e8cc0c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nivolumab|CP & Nivolumab]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29_.26_Nivolumab|CVb & Nivolumab]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Nivolumab|DC & Nivolumab]]
 +
| style="background-color:#d73027" |Inferior EFS
 +
|-
 +
|}
 +
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 or 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]], then adjuvant therapy
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 85/100 x 3 {{#subobject:e8cc0c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(15)60294-X Pless et al. 2015 (SAKK 16/00)]
 +
|2001-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]], then [[#Radiation_therapy_99|RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*Stage IIIA or N2 NSCLC
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV once on day 1
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]]
 +
</div></div>
 +
===References===
 +
#'''SAKK 16/00:''' Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S, Gerard MA, Xyrafas A, Früh M, Cathomas R, Zippelius A, Roth A, Bijelovic M, Ochsenbein A, Meier UR, Mamot C, Rauch D, Gautschi O, Betticher DC, Mirimanoff RO, Peters S; SAKK Lung Cancer Project Group. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. 2015 Sep 12;386(9998):1049-56. Epub 2015 Aug 11. Erratum in: Lancet. 2015 Sep 12;386(9998):1040. [https://doi.org/10.1016/S0140-6736(15)60294-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26275735 PubMed] NCT00030771
 +
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
 +
#'''CheckMate 77T:''' NCT04025879
 +
==Cisplatin & Docetaxel (DC) & Durvalumab {{#subobject:ca8gb8|Regimen=1}}==
 +
DC & Durvalumab: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, Durvalumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1jgu0c|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 28: Line 202:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://doi.org/10.1200/jco.21.00276 Rothschild et al. 2021 (SAKK 16/14)]
−
|1996-2001
+
|2016-2019
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(15)01317-3 Ribrag et al. 2016 (LMBA-02)]
+
|}
−
|2004-2010
+
<div class="toccolours" style="background-color:#fdcdac">
−
|style="background-color:#91cf61"|Non-randomized portion of phase 3 RCT
+
====Eligibility criteria====
 +
*Stage IIIA(N2) NSCLC
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] as follows:
 +
**Cycles 1 to 3: 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Docetaxel (Taxotere)]] as follows:
 +
**Cycles 1 to 3: 85 mg/m<sup>2</sup> IV once on day 1
 +
====Immunotherapy====
 +
*[[Durvalumab (Imfinzi)]] as follows:
 +
**Cycles 4 & 5: 750 mg IV once on day 1
 +
 +
'''21-day cycle for 3 cycles, then 14-day cycle for 2 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]], then adjuvant [[#Durvalumab_monotherapy_88|durvalumab]]
 +
</div></div>
 +
===References===
 +
#'''SAKK 16/14:''' Rothschild SI, Zippelius A, Eboulet EI, Savic Prince S, Betticher D, Bettini A, Früh M, Joerger M, Lardinois D, Gelpke H, Mauti LA, Britschgi C, Weder W, Peters S, Mark M, Cathomas R, Ochsenbein AF, Janthur WD, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M; Swiss Group for Clinical Cancer Research (SAKK). SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol. 2021 Sep 10;39(26):2872-2880. Epub 2021 Jul 12. [https://doi.org/10.1200/jco.21.00276 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34251873/ PubMed] NCT02572843
 +
==Cisplatin & Docetaxel (DC) & Nivolumab {{#subobject:cab6rr|Regimen=1}}==
 +
DC & Nivolumab: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, Nivolumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:ug8z0c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|CVb]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29|DC]]
 +
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 31.6 vs 20.8 mo<br>(HR 0.63, 97.38% CI 0.43-0.91)<br><br>Superior pCR rate<br>24% vs 2.2%<br>(OR 13.94, 99% CI 3.49-55.75)
 
|-
 
|-
 
|}
 
|}
 +
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.''
 
<div class="toccolours" style="background-color:#fdcdac">
 
<div class="toccolours" style="background-color:#fdcdac">
−
====Eligibility criteria====
+
====Biomarker eligibility criteria====
−
*Group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement)
+
*CheckMate 816: No sensitizing EGFR or ALK mutations
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 300 mg/m<sup>2</sup> IV once on day 1
+
*[[Docetaxel (Taxotere)]] 60 or 75 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
−
====Glucocorticoid therapy====
+
====Immunotherapy====
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 7
+
*[[Nivolumab (Opdivo)]] 360 mg IV once on day 1
−
====CNS therapy, prophylaxis (group B)====
+
'''21-day cycle for 3 cycles'''
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 1
+
</div>
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once on day 1 (admixed with MTX)
+
<div class="toccolours" style="background-color:#cbd5e7">
−
====CNS therapy, treatment (group C)====
+
====Subsequent treatment====
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1, 3, 5
+
*[[Surgery#Surgical_resection|Complete resection]], then adjuvant therapy
−
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1, 3, 5
+
</div></div>
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 1, 3, 5 (admixed with MTX & Ara-C)
+
===References===
−
'''One course'''
+
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
 +
==Cisplatin & Etoposide (EP) {{#subobject:gocg67|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a17gyz5|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/s1470-2045(08)70156-6 Thomas et al. 2008 (GLCCG 01/95)]
 +
|1995-2003
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
|-
 +
|}
 +
''Note: abstract does not contain dosing details.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]]
 +
*[[Etoposide (Vepesid)]]
 +
'''3 cycles'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*LMB95: [[#COPADM|COPADM]]
+
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], then [[Non-small_cell_lung_cancer#Radiation_therapy|RT]] versus [[#Carboplatin.2C_Vindesine.2C_RT_88|Carboplatin, Vindesine, RT]], then [[Surgery#Lung_cancer_surgery|surgical resection]]
−
*LMBA-02: [[#COPADM|COPADM]] versus [[#R-COPADM|R-COPADM]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''GLCCG 01/95:''' Thomas M, Rübe C, Hoffknecht P, Macha HN, Freitag L, Linder A, Willich N, Hamm M, Sybrecht GW, Ukena D, Deppermann KM, Dröge C, Riesenbeck D, Heinecke A, Sauerland C, Junker K, Berdel WE, Semik M; German Lung Cancer Cooperative Group. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol. 2008 Jul;9(7):636-48. Epub 2008 Jun 24. [https://doi.org/10.1016/s1470-2045(08)70156-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18583190/ PubMed] NCT00176137
−
# '''LMBA-02:''' Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. [https://doi.org/10.1016/S0140-6736(15)01317-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27080498 PubMed] NCT00180882
+
==Cisplatin & Gemcitabine (GC) {{#subobject:c567c5|Regimen=1}}==
−
==Cyclophosphamide & Prednisone {{#subobject:44cd80|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 1000/300 {{#subobject:4f2b02|Variant=1}}===
+
===Regimen variant #1, 75/2000 {{#subobject:b009h1|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (KEYNOTE 671)
 +
|2018-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Pembrolizumab_66|GC & Pembrolizumab]]<br>2. [[#Cisplatin.2C_Pemetrexed.2C_Pembrolizumab_66|Pem-Cis & Pembrolizumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.23522 Oriol et al. 2008]
+
|}
−
|style="background-color:#91cf61"|Non-randomized
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 4 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]]
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75/2500 x 3 {{#subobject:b0097e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271177/ Hoelzer et al. 2014 (GMALL-B-ALL/NHL 2002)]
+
|[https://doi.org/10.1200/JCO.2010.33.7089 Scagliotti et al. 2011 (CHEST)]
−
|style="background-color:#91cf61"|Non-randomized
+
|2000-2004
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 7.8 vs 4.8 y<br>(aHR 0.63, 95% CI 0.43-0.92)
 
|-
 
|-
 
|}
 
|}
−
''Note: GMALL-B-ALL/NHL 2002 is fairly similar to the [[Burkitt_lymphoma#GMALL-R|GMALL-R regimen]], with some minor differences. See text for details.''
+
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*Stage IB to IIIA NSCLC
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given at least 4 hours after gemcitabine'''
−
====Glucocorticoid therapy====
+
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 5
+
'''21-day cycle for 3 cycles'''
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT once on day 1, admixed with methotrexate and dexamethasone
 
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 1, admixed with cytarabine and dexamethasone
 
−
*[[Dexamethasone (Decadron)]] 20 mg IT once on day 1, admixed with cytarabine and methotrexate
 
−
'''One course'''
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*Oriol et al. 2008: PETHEMA induction; see text for details
+
*[[Surgery#Surgical_resection|Complete resection]], 2 to 6 weeks after last dose of chemotherapy
−
*GMALL-B-ALL/NHL 2002: Induction; see text for details
 
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, 1000/420 {{#subobject:73d35c|Variant=1}}===
+
===Regimen variant #3, 75/2500 x 4 {{#subobject:b1o9h1|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (IMpower030)
 +
|2018-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin.2C_nab-Paclitaxel.2C_Atezolizumab_66|Carboplatin, nab-Paclitaxel, Atezolizumab]]<br>2. [[#Carboplatin.2C_Pemetrexed.2C_Atezolizumab_66|Carboplatin, Pemetrexed, Atezolizumab]]<br>3. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Atezolizumab_66|GC & Atezolizumab]]<br>4. [[#Cisplatin.2C_Pemetrexed.2C_Atezolizumab_66|Pem-Cis & Atezolizumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 4 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]]
 +
</div></div>
 +
===References===
 +
#'''CHEST:''' Scagliotti GV, Pastorino U, Vansteenkiste JF, Spaggiari L, Facciolo F, Orlowski TM, Maiorino L, Hetzel M, Leschinger M, Visseren-Grul C, Torri V. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol. 2012 Jan 10;30(2):172-8. Epub 2011 Nov 28. [https://doi.org/10.1200/JCO.2010.33.7089 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22124104 PubMed] NCT00191126
 +
#'''AEGEAN:''' NCT03800134
 +
#'''KEYNOTE 671:''' NCT03425643
 +
#'''IMpower030:''' NCT03456063
 +
==Cisplatin & Vinorelbine (CVb) {{#subobject:uuhz8q|Regimen=1}}==
 +
CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1yjxx7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Nivolumab|CP & Nivolumab]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29_.26_Nivolumab|CVb & Nivolumab]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Nivolumab|DC & Nivolumab]]
 +
| style="background-color:#d73027" |Inferior EFS
 
|-
 
|-
−
|[https://doi.org/10.1200/JCO.2001.19.20.4014 Lee et al. 2001 (CALGB 9251)]
+
|}
−
|style="background-color:#91cf61"|Non-randomized
+
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 25 or 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 3 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[Surgery#Surgical_resection|Complete resection]], then adjuvant therapy
 +
</div></div>
 +
===References===
 +
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
 +
==Cisplatin & Vinorelbine (CVb) & Nivolumab {{#subobject:7y19op|Regimen=1}}==
 +
CVb & Nivolumab: '''<u>C</u>'''isplatin, '''<u>V</u>'''inorel'''<u>b</u>'''ine, Nivolumab
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:ug8oxc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996561/ Rizzieri et al. 2014 (CALGB 10-002)]
+
|[https://doi.org/10.1056/nejmoa2202170 Forde et al. 2022 (CheckMate 816)]
−
|style="background-color:#91cf61"|Phase 2
+
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>2. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|CVb]]<br>3. [[#Cisplatin_.26_Docetaxel_.28DC.29|DC]]
 +
| style="background-color:#1a9850" |Superior EFS<br>Median EFS: 31.6 vs 20.8 mo<br>(HR 0.63, 97.38% CI 0.43-0.91)<br><br>Superior pCR rate<br>24% vs 2.2%<br>(OR 13.94, 99% CI 3.49-55.75)
 
|-
 
|-
 
|}
 
|}
−
''Note: CALGB 9251 is an earlier version of CALGB 10-002 that demonstrated that cranial radiation can be omitted in the treatment of Burkitt lymphoma.''
+
''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*CheckMate 816: No sensitizing EGFR or ALK mutations
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
−
====Glucocorticoid therapy====
+
*[[Vinorelbine (Navelbine)]] 25 or 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 7
+
====Immunotherapy====
−
====Supportive therapy====
+
*[[Nivolumab (Opdivo)]] 360 mg IV once on day 1
−
*[[Allopurinol (Zyloprim)]] 300 mg PO once per day on days 1 to 14 (includes first week of cycle 2)
+
'''21-day cycle for 3 cycles'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*CALGB 9251: See text for details
+
*[[Surgery#Surgical_resection|Complete resection]], then adjuvant therapy
−
*CALGB 10-002: [[#CALGB_10-002_regimen|CALGB 10-002 main regimen]]
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''CALGB 9251:''' Lee EJ, Petroni GR, Schiffer CA, Freter CE, Johnson JL, Barcos M, Frizzera G, Bloomfield CD, Peterson BA. Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of Cancer and Leukemia Group B study 9251. J Clin Oncol. 2001 Oct 15;19(20):4014-22. [https://doi.org/10.1200/JCO.2001.19.20.4014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11600602 PubMed]
+
#'''CheckMate 816:''' Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. [https://doi.org/10.1056/nejmoa2202170 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35403841/ PubMed] NCT02998528
−
## '''Update:''' Rizzieri DA, Johnson JL, Niedzwiecki D, Lee EJ, Vardiman JW, Powell BL, Barcos M, Bloomfield CD, Schiffer CA, Peterson BA, Canellos GP, Larson RA. Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer. 2004 Apr 1;100(7):1438-48. [https://doi.org/10.1002/cncr.20143 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15042678 PubMed]
+
=Adjuvant therapy=
−
<!-- Results previously presented at the 49th ASH Annual Meeting, Atlanta, Georgia, December 8-11, 2007. -->
+
==Atezolizumab monotherapy {{#subobject:41gac4|Regimen=1}}==
−
# Oriol A, Ribera JM, Bergua J, Giménez Mesa E, Grande C, Esteve J, Brunet S, Moreno MJ, Escoda L, Hernandez-Rivas JM, Hoelzer D; PETHEMA. High-dose chemotherapy and immunotherapy in adult Burkitt lymphoma: comparison of results in human immunodeficiency virus-infected and noninfected patients. Cancer. 2008 Jul 1;113(1):117-25. [https://doi.org/10.1002/cncr.23522 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18457327 PubMed]
+
<div class="toccolours" style="background-color:#eeeeee">
−
# '''CALGB 10-002:''' Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology. Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: Cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. Epub 2014 Jan 15. [https://doi.org/10.1111/bjh.12736 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996561/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24428673 PubMed]
+
===Regimen variant #1, q2wk {{#subobject:1gc67u|Variant=1}}===
−
# '''GMALL-B-ALL/NHL 2002:''' Hoelzer D, Walewski J, Döhner H, Viardot A, Hiddemann W, Spiekermann K, Serve H, Dührsen U, Hüttmann A, Thiel E, Dengler J, Kneba M, Schaich M, Schmidt-Wolf IG, Beck J, Hertenstein B, Reichle A, Domanska-Czyz K, Fietkau R, Horst HA, Rieder H, Schwartz S, Burmeister T, Gökbuget N; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014 Dec 18;124(26):3870-9. Epub 2014 Oct 30. [http://www.bloodjournal.org/content/124/26/3870 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271177/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25359988 PubMed]
+
{| class="wikitable" style="color:white; background-color:#404040"
−
 
+
|<small>'''FDA-recommended dose'''</small>
−
=Untreated=
+
|-
−
==BASIC {{#subobject:eb66c6|Regimen=1}}==
+
|}
−
BASIC: '''<u>B</u>'''rief, '''<u>A</u>'''nthracycline-'''<u>S</u>'''paring, '''<u>I</u>'''ntensive '''<u>C</u>'''yclophosphamide
+
''Note: This is not the dose/schedule used in the registration trial.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Lung_cancer_surgery|Resection]] and [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Atezolizumab (Tecentriq)]] 840 mg IV once on day 1
 +
'''14-day cycle for 26 cycles (1 year)'''
 +
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:301df4|Variant=1}}===
+
===Regimen variant #2, q3wk {{#subobject:1gc57f|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable" style="color:white; background-color:#404040"
−
!style="width: 25%"|Study
+
|<small>'''FDA-recommended dose'''</small>
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(21)02098-5 Felip et al. 2021 (IMpower010)]
 +
|2015-2018
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Best supportive care]]
 +
| style="background-color:#91cf60" |Seems to have superior DFS<br>Median DFS: NYR vs 37.2 mo<br>(HR 0.81, 95% CI 0.67-0.99)
 +
|-
 +
|}
 +
''Note: Cisplatin & Pemetrexed was only offered to patients with nonsquamous histology.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]] x 4 or [[#Cisplatin_.26_Docetaxel_.28DC.29_2|DC]] x 4 or [[#Cisplatin_.26_Gemcitabine_.28GC.29_2|GC]] x 4 or [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]] x 4
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
 +
'''21-day cycle for up to 16 cycles (1 year)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, q4wk {{#subobject:1ga67u|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
''Note: This is not the dose/schedule used in the registration trial.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Lung_cancer_surgery|Resection]] and [[Regimen_classes#Platinum-based_regimen|platinum-based chemotherapy]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Atezolizumab (Tecentriq)]] 1680 mg IV once on day 1
 +
'''28-day cycle for 13 cycles (1 year)'''
 +
</div></div>
 +
===References===
 +
#'''IMpower010:''' Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. [https://doi.org/10.1016/s0140-6736(21)02098-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34555333/ PubMed] NCT02486718
 +
==Carboplatin & Paclitaxel (CP) {{#subobject:3a6ad9|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:59db47|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652093/ Strauss et al. 2008 (CALGB 9633)]
 +
|1996-2003
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[Surgery#Lobectomy|Lobectomy]] or [[Surgery#Pneumonectomy|pneumonectomy]], within 4 to 8 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 45 to 60 minutes once on day 1
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 +
'''21-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA, and at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA. -->
 +
#'''CALGB 9633:''' Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. [https://doi.org/10.1200/jco.2008.16.4855 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2652093/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18809614 PubMed] NCT00002852
 +
#'''IFCT 0002:''' Westeel V, Quoix E, Puyraveau M, Lavolé A, Braun D, Laporte S, Bigay-Game L, Pujol JL, Ozenne G, Rivière A, Douillard JY, Lebeau B, Debieuvre D, Poudenx M, David P, Molinier O, Zalcman G, Lemarié E, Morin F, Depierre A, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial). Eur J Cancer. 2013 Aug;49(12):2654-64. Epub 2013 Jun 1. [https://doi.org/10.1016/j.ejca.2013.04.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23735703/ PubMed] NCT00198354
 +
==Cisplatin & Docetaxel (DC) {{#subobject:211cca|Regimen=1}}==
 +
DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:bc45d4|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[http://icvts.oxfordjournals.org/content/20/6/783.long Barlesi et al. 2015]
 +
|2004-2007
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]]
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(17)30691-5 Wakelee et al. 2017 (ECOG-ACRIN E1505)]
 +
|2007-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Bevacizumab_99|DC & Bevacizumab]]<br>2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Bevacizumab_99|GC & Bevacizumab]]<br> 3. [[#Cisplatin.2C_Pemetrexed.2C_Bevacizumab_99|Cisplatin, Pemetrexed, Bevacizumab]]<br>4. [[#Cisplatin.2C_Vinorelbine.2C_Bevacizumab_99|Cisplatin, Vinorelbine, Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Barlesi et al. 2015: Complete R0 [[Surgery#Lung_cancer_surgery|resection]], within 8 weeks
 +
*ECOG-ACRIN E1505: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles (Barlesi et al. 2015) or 4 cycles (ECOG-ACRIN E1505)'''
 +
</div></div>
 +
===References===
 +
#Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25765952 PubMed]
 +
#'''ECOG-ACRIN E1505:''' Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30691-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29129443 PubMed] NCT00324805
 +
#'''IMpower010:''' Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. [https://doi.org/10.1016/s0140-6736(21)02098-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34555333/ PubMed] NCT02486718
 +
==Cisplatin & Etoposide (EP) {{#subobject:dbad67|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a211c5|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa031644 Arriagada et al. 2004 (IALT)]
 +
|1995-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>OS60: 44.5% vs 40.4%<br>(HR 0.86, 95% CI 0.76-0.98)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 60 days
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
'''28-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#'''IALT:''' Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [https://doi.org/10.1056/NEJMoa031644 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14736927 PubMed] NCT00002823
 +
##'''Update:''' Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. [https://doi.org/10.1200/JCO.2009.23.2272 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19933916 PubMed]
 +
==Cisplatin & Gemcitabine (GC) {{#subobject:289ea6|Regimen=1}}==
 +
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 75/1200 x 4 {{#subobject:4cd112|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(17)30691-5 Wakelee et al. 2017 (ECOG-ACRIN E1505)]
 +
|2007-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Bevacizumab_99|DC & Bevacizumab]]<br>2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Bevacizumab_99|GC & Bevacizumab]]<br> 3. [[#Cisplatin.2C_Pemetrexed.2C_Bevacizumab_99|Cisplatin, Pemetrexed, Bevacizumab]]<br>4. [[#Cisplatin.2C_Vinorelbine.2C_Bevacizumab_99|Cisplatin, Vinorelbine, Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75/1250 x 3 {{#subobject:22cb4c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[http://icvts.oxfordjournals.org/content/20/6/783.long Barlesi et al. 2015]
 +
|2004-2007
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Docetaxel_.28DC.29_2|Cisplatin & Docetaxel]]
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*Stage IB–III NSCLC
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Preceding treatment====
 +
*Complete R0 [[Surgery#Lung_cancer_surgery|resection]], within 8 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 3 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 75/1250 x 4 {{#subobject:22cg7c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 +
!style="width: 33%"|Study
 +
!style="width: 33%"|Years of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234101/ Kasamon et al. 2012 (J0409)]
+
|[https://doi.org/10.1016/s0140-6736(21)02098-5 Felip et al. 2021 (IMpower010)]
−
|style="background-color:#91cf61"|Non-randomized
+
|2015-2018
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|resection]], within 4 to 12 weeks
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 1500 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 2 hours once on day 8
+
'''21-day cycle for 4 cycles'''
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
 
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] 900 mg/m<sup>2</sup> IV in divided doses on day 1
 
−
*[[Folinic acid (Leucovorin)]] 25 mg/m<sup>2</sup> IV Q6H, starting 24 hours after start of IV [[Methotrexate (MTX)]], until clearance
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 3 and continuing until post-nadir ANC greater than 500/uL
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 100 mg IT once per day on days 1, 4, 11 (also day 8 if no IV MTX given)
 
−
*[[Hydrocortisone (Cortef)]] 50 mg IT is optional (no parameters given)
 
−
'''14-day cycle for 2 cycles'''
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*[[#BASIC_2|BASIC intensification]]
+
*[[#Atezolizumab_monotherapy|Atezolizumab]] versus [[Non-small_cell_lung_cancer_-_null_regimens#Observation|Best supportive care]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 2009 American Society of Hematology annual meeting -->
+
#Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25765952 PubMed]
−
# '''J0409:''' Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. [https://doi.org/10.3109/10428194.2012.715346 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234101/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22835045 PubMed]
+
#'''ECOG-ACRIN E1505:''' Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30691-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29129443 PubMed] NCT00324805
−
==CALGB 10-002 regimen {{#subobject:12cddc|Regimen=1}}==
+
#'''IMpower010:''' Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. [https://doi.org/10.1016/s0140-6736(21)02098-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34555333/ PubMed] NCT02486718
 +
#'''ACCIO:''' NCT04267848
 +
==Cisplatin & Pemetrexed {{#subobject:1caad6|Regimen=1}}==
 +
CPx: '''<u>C</u>'''isplatin & '''<u>P</u>'''emetre'''<u>x</u>'''ed
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:36626c|Variant=1}}===
+
===Regimen {{#subobject:73f03b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 17%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mds578 Kreuter et al. 2013 (TREAT)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 +
|[[#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet secondary endpoint of OS<sup>1</sup>
 +
| style="background-color:#1a9850" |Superior clinical feasibility rate
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(17)30691-5 Wakelee et al. 2017 (ECOG-ACRIN E1505)]
 +
|2007-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Bevacizumab_99|DC & Bevacizumab]]<br>2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Bevacizumab_99|GC & Bevacizumab]]<br> 3. [[#Cisplatin.2C_Pemetrexed.2C_Bevacizumab_99|Cisplatin, Pemetrexed, Bevacizumab]]<br>4. [[#Cisplatin.2C_Vinorelbine.2C_Bevacizumab_99|Cisplatin, Vinorelbine, Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://www.nature.com/articles/s41416-019-0533-3 Groen et al. 2019 (NVALT-8)]
 +
|2007-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin.2C_Pemetrexed.2C_Nadroparin_77|CPx & Nadroparin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 +
|
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy for TREAT is based on the 2016 update.''<br>
 +
''Note: In TREAT, this treatment was intended for pathologically confirmed NSCLC stages (according to the TNM staging system version 6) IB, IIA, IIB or T3N1.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*TREAT & NVALT-8: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 4 to 6 weeks
 +
*ECOG-ACRIN E1505: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#'''TREAT:''' Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG Leuven Lung Cancer Group. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [https://doi.org/10.1093/annonc/mds578 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23161898 PubMed] NCT00349089
 +
##'''Update:''' Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. [http://www.jto.org/article/S1556-0864(15)00023-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26762743 PubMed]
 +
#'''ECOG-ACRIN E1505:''' Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30691-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29129443 PubMed] NCT00324805
 +
#'''NVALT-8:''' Groen HJM, van der Heijden EHFM, Klinkenberg TJ, Biesma B, Aerts J, Verhagen A, Kloosterziel C, Pieterman R, van den Borne B, Smit HJM, Hoekstra O, Schramel FMNH, van der Noort V, van Tinteren H, Smit EF, Dingemans AC; NVALT Study Group. Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study. Br J Cancer. 2019 Aug;121(5):372-377. Epub 2019 Jul 24. [https://www.nature.com/articles/s41416-019-0533-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31337877 PubMed] NTR1250/1217
 +
#'''IMpower010:''' Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. [https://doi.org/10.1016/s0140-6736(21)02098-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34555333/ PubMed] NCT02486718
 +
==Cisplatin & Vinblastine {{#subobject:af5cc1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1d592|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa031644 Arriagada et al. 2004 (IALT)]
 +
|1995-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>OS60: 44.5% vs 40.4%<br>(HR 0.86, 95% CI 0.76-0.98)
 +
|-
 +
|}
 +
''Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vinblastine schedule is extrapolated from regimen information in Table 1 in which vinblastine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 60 days
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 22, 43, 64
 +
*[[Vinblastine (Velban)]] 4 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 43, 57
 +
'''12-week course'''
 +
</div></div>
 +
===References===
 +
#'''IALT:''' Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [https://doi.org/10.1056/NEJMoa031644 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14736927 PubMed] NCT00002823
 +
##'''Update:''' Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. [https://doi.org/10.1200/JCO.2009.23.2272 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19933916 PubMed]
 +
==Cisplatin & Vindesine {{#subobject:80fe2|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:2d16cd|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa031644 Arriagada et al. 2004 (IALT)]
 +
|1995-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>OS60: 44.5% vs 40.4%<br>(HR 0.86, 95% CI 0.76-0.98)
 +
|-
 +
|}
 +
''Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vindesine schedule is extrapolated from regimen information in Table 1 in which vindesine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 60 days
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 22, 43, 64
 +
*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 43, 57
 +
'''12-week course'''
 +
</div></div>
 +
===References===
 +
#'''IALT:''' Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [https://doi.org/10.1056/NEJMoa031644 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14736927 PubMed] NCT00002823
 +
##'''Update:''' Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. [https://doi.org/10.1200/JCO.2009.23.2272 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19933916 PubMed]
 +
==Cisplatin & Vinorelbine (CVb) {{#subobject:ab1b88|Regimen=1}}==
 +
CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, cisplatin 50 mg/m<sup>2</sup>, 2 weeks out of 4 {{#subobject:c1a368|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa043623 Winton et al. 2005 (JBR.10)]
 +
|1994-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 94 vs 73 mo<br>(HR 0.69, 95% CI 0.52-0.91)
 +
|
 +
|-
 +
|[https://doi.org/10.1093/annonc/mds578 Kreuter et al. 2013 (TREAT)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]
 +
| style="background-color:#ffffbf" |Did not meet secondary endpoint of OS<sup>1</sup>
 +
| style="background-color:#1a9850" |Superior clinical feasibility rate
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy for TREAT is based on the 2016 update.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*JBR.10: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 weeks
 +
*TREAT: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 4 to 6 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
'''28-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, cisplatin 75 mg/m<sup>2</sup>, q3wk {{#subobject:04b3e6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(17)30691-5 Wakelee et al. 2017 (ECOG-ACRIN E1505)]
 +
|2007-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_.26_Bevacizumab_99|DC & Bevacizumab]]<br>2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Bevacizumab_99|GC & Bevacizumab]]<br> 3. [[#Cisplatin.2C_Pemetrexed.2C_Bevacizumab_99|Cisplatin, Pemetrexed, Bevacizumab]]<br>4. [[#Cisplatin.2C_Vinorelbine.2C_Bevacizumab_99|Cisplatin, Vinorelbine, Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, cisplatin 100 mg/m<sup>2</sup>, q4wk {{#subobject:6edee|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(06)70804-X Douillard et al. 2006 (ANITA)]
 +
|1994-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa031644 Arriagada et al. 2004 (IALT)]
 +
|1995-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation|Observation]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>OS60: 44.5% vs 40.4%<br>(HR 0.86, 95% CI 0.76-0.98)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*IALT: Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 60 days
 +
*ANITA: Complete [[Surgery#Lung_cancer_surgery|surgical resection]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
'''28-day cycle for 4 cycles'''
 +
</div></div>
 +
===References===
 +
#'''IALT:''' Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [https://doi.org/10.1056/NEJMoa031644 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14736927 PubMed] NCT00002823
 +
##'''Update:''' Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. [https://doi.org/10.1200/JCO.2009.23.2272 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19933916 PubMed]
 +
#'''JBR.10:''' Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. [https://doi.org/10.1056/NEJMoa043623 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15972865 PubMed] NCT00002583
 +
##'''Update:''' Butts CA, Ding K, Seymour L, Twumasi-Ankrah P, Graham B, Gandara D, Johnson DH, Kesler KA, Green M, Vincent M, Cormier Y, Goss G, Findlay B, Johnston M, Tsao MS, Shepherd FA. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol. 2010 Jan 1;28(1):29-34. Epub 2009 Nov 23. [https://doi.org/10.1200/JCO.2009.24.0333 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2799232/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19933915 PubMed]
 +
#'''ANITA:''' Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Rodrigues Pereira J, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. [https://doi.org/10.1016/S1470-2045(06)70804-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/16945766 PubMed] NCT00576914
 +
#'''TREAT:''' Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [https://doi.org/10.1093/annonc/mds578 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23161898 PubMed] NCT00349089
 +
##'''Update:''' Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. [http://www.jto.org/article/S1556-0864(15)00023-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26762743 PubMed]
 +
#'''ECOG-ACRIN E1505:''' Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30691-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29129443 PubMed] NCT00324805
 +
#'''IMpower010:''' Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. [https://doi.org/10.1016/s0140-6736(21)02098-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34555333/ PubMed] NCT02486718
 +
==Pembrolizumab monotherapy {{#subobject:i9gx51|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:xcczeb|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/s1470-2045(22)00518-6 O'Brien et al. 2022 (PEARLS)]
 +
|2016-2020
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo|Placebo]]
 +
| style="background-color:#1a9850" |Superior DFS<br>Median DFS: 53.6 vs 42 mo<br>(HR 0.76, 95% CI 0.63-0.91)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 +
'''21-day cycle for up to 18 cycles'''
 +
</div></div>
 +
===References===
 +
# '''PEARLS:''' O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, Esteban E, Isla D, Martinez-Marti A, Faehling M, Tsuboi M, Lee JS, Nakagawa K, Yang J, Samkari A, Keller SM, Mauer M, Jha N, Stahel R, Besse B, Peters S; EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Sep 9. Epub ahead of print. [https://doi.org/10.1016/s1470-2045(22)00518-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36108662/ PubMed] NCT02504372
 +
==Radiation therapy {{#subobject:6a88uu|Regimen=1}}==
 +
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1tgv26|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (KEYNOTE-867)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_.26_RT_66|Pembrolizumab & RT]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|Awaiting publication (PACIFIC-4)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Durvalumab_.26_RT_66|Durvalumab & RT]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|Awaiting publication (SWOG S1914)
 +
|2020-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Atezolizumab_.26_RT_66|Atezolizumab & RT]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Radiotherapy====
 +
*[[External beam radiotherapy]]
 +
</div></div>
 +
===References===
 +
#'''KEYNOTE-867:''' NCT03924869
 +
#'''PACIFIC-4:''' NCT03833154
 +
#'''SWOG S1914:''' NCT04214262
 +
==Tegafur & uracil monotherapy {{#subobject:ac88ea|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:b0fe3f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996561/ Rizzieri et al. 2014 (CALGB 10-002)]
+
|[https://doi.org/10.1007/s10147-021-02012-9 Yamaguchi et al. 2021 (WJTOG0101)]
−
|style="background-color:#91cf61"|Phase 2
+
|2001-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_monotherapy_99|Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS60: 68.8% vs 70%<br>(HR 1.05, 95% CI 0.81-1.37)
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*Stage IB-IIIA NSCLC, with complete resection
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#Cyclophosphamide_.26_Prednisone|Cyclophosphamide & Prednisone pre-phase]]
+
*[[Surgery#Lung_cancer_surgery|Surgery]]
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, A cycles====
+
====Chemotherapy====
−
*[[Ifosfamide (Ifex)]] as follows:
+
*[[Tegafur and uracil (UFT)]] 250 mg/m<sup>2</sup>/day PO (rounded up or down to the nearest 100 mg)
−
**Cycles 2, 4, 6: 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
'''1-year course'''
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 2, 4, 6: 150 mg/m<sup>2</sup> IV bolus once on day 1, then 1350 mg/m<sup>2</sup> IV continuous infusion over 23.5 hours (total dose per cycle: 1500 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 2, 4, 6: 2 mg IV push once on day 1
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 2, 4, 6: 1000 mg/m<sup>2</sup> IV over 2 hours once per day on days 4 & 5
 
−
*[[Etoposide (Vepesid)]] as follows:
 
−
**Cycles 2, 4, 6: 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 4 & 5
 
−
====Glucocorticoid therapy, A cycles====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 2, 4, 6: 10 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 5
 
−
====Targeted therapy, A cycles====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycle 2: 50 mg/m<sup>2</sup> IV once on day 8, then 375 mg/m<sup>2</sup> IV once per day on days 10 & 12
 
−
**Cycles 4 & 6: 375 mg/m<sup>2</sup> IV once on day 8
 
−
====CNS therapy, prophylaxis, A cycles====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 2, 4, 6: 40 mg IT on day 1
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 2, 4, 6: 15 mg IT on day 1
 
−
*[[Hydrocortisone (Cortef)]] as follows:
 
−
**Cycles 2, 4, 6: 50 mg IT on day 1
 
−
====Supportive therapy, A cycles====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycles 2, 4, 6: (dose not specified but presumably equal to ifosfamide dose) mixed with [[Ifosfamide (Ifex)]]
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycles 2, 4, 6: 25 mg/m<sup>2</sup> IV or PO once 36 hours after start of IV methotrexate, then 10 mg/m<sup>2</sup> every 6 hours until methotrexate level less than 50 nmol/L
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycles 2, 4, 6: 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 500/uL
 
−
====Chemotherapy, B cycles====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 3, 5, 7: 200 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 3, 5, 7: 150 mg/m<sup>2</sup> IV bolus once on day 1, then 1350 mg/m<sup>2</sup> IV continuous infusion over 23.5 hours (total dose per cycle: 1500 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 3, 5, 7: 2 mg IV push once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 3, 5, 7: 25 mg/m<sup>2</sup> IV once per day on days 4 & 5
 
−
====Glucocorticoid therapy, B cycles====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 3, 5, 7: 10 mg/m<sup>2</sup> IV or PO once per day on days 1 to 5
 
−
====Targeted therapy, B cycles====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 3, 5, 7: 375 mg/m<sup>2</sup> IV once on day 8
 
−
====CNS therapy, prophylaxis, B cycles====
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 3, 5, 7: 40 mg IT on day 1
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 3, 5, 7: 15 mg IT on day 1
 
−
*[[Hydrocortisone (Cortef)]] as follows:
 
−
**Cycles 3, 5, 7: 50 mg IT on day 1
 
−
====Supportive therapy, B cycles====
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycles 3, 5, 7: 50 mg/m<sup>2</sup> IV or PO once 36 hours after start of IV methotrexate, then 10 mg/m<sup>2</sup> every 6 hours until methotrexate level less than 50 nmol/L
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycles 3, 5, 7: 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 500/uL
 
−
'''21-day cycle for 6 cycles'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''CALGB 10-002:''' Rizzieri DA, Johnson JL, Byrd JC, Lozanski G, Blum KA, Powell BL, Shea TC, Nattam S, Hoke E, Cheson BD, Larson RA; Alliance for Clinical Trials In Oncology (ACTION). Improved efficacy using rituximab and brief duration, high intensity chemotherapy with filgrastim support for Burkitt or aggressive lymphomas: Cancer and Leukemia Group B study 10 002. Br J Haematol. 2014 Apr;165(1):102-11. Epub 2014 Jan 15. [https://doi.org/10.1111/bjh.12736 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996561/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24428673 PubMed]
+
#'''WJTOG0101:''' Yamaguchi M, Tada H, Mitsudomi T, Seto T, Yokoi K, Katakami N, Nakagawa K, Oda M, Ohta M, Sawa T, Yamashita M, Iked N, Saka H, Higashiyama M, Nomori H, Semba H, Negoro S, Chiba Y, Shimokawa M, Fukuoka M, Nakanishi Y; West Japan Thoracic Oncology Group (WJTOG). Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101). Int J Clin Oncol. 2021 Dec;26(12):2216-2223. Epub 2021 Aug 31. [https://doi.org/10.1007/s10147-021-02012-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34463869/ PubMed] NCT00139971
−
==CODOX-M {{#subobject:383ac6|Regimen=1}}==
+
=Induction chemotherapy for locally advanced disease=
−
CODOX-M: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate
+
==Carboplatin & Paclitaxel (CP) {{#subobject:b2de53|Regimen=1}}==
 +
PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, "Original Magrath" {{#subobject:41cf47|Variant=1}}===
+
===Regimen variant #1, 6/200 {{#subobject:4d4e46|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.05.4163 Huber et al. 2006 (CTRT99/97)]
 +
|1997-2002
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.55.405 Belani et al. 2005 (LAMP)]
 +
|1998-2001
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.1996.14.3.925 Magrath et al. 1996 (NCI 89-C-41)]
+
|[https://doi.org/10.1200/JCO.2006.07.3569 Vokes et al. 2007 (CALGB 39801)]
−
|style="background-color:#91cf61"|Phase 2
+
|1998-2002
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#No_induction|No]] induction
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen variant is intended for low-risk patients.''
+
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1, '''given second'''
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
'''21-day cycle for 2 cycles'''
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
+
</div>
−
**65 years or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
+
<div class="toccolours" style="background-color:#cbd5e7">
−
**Older than 65 years: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
+
====Subsequent treatment====
−
====Supportive therapy====
+
*LAMP: [[#Radiation_therapy_2|RT]] x 63 Gy
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV Q3H, starting 36 hours after start of IV [[Methotrexate (MTX)]] until 48 hours, then every 6 hours until methotrexate level undetectable
+
*CTRT99/97: [[#Paclitaxel_.26_RT_99|Paclitaxel & RT]] versus [[#Radiation_therapy_2|RT]]
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal [[Methotrexate (MTX)]]
+
*CALGB 39801: [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|Carboplatin, Paclitaxel, RT]]
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
'''3 cycles'''
 
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #2, "Modified Magrath" {{#subobject:d69e9b|Variant=1}}===
+
===Regimen variant #2, 6/225 {{#subobject:1ec13b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ Hoang et al. 2012 (ECOG 3598)]
 +
|2000-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Complex_multipart_regimens#ECOG_3598|See link]]
 +
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#ECOG_3598|See link]]
 +
|-
 +
|}
 +
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 2 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|Carboplatin, Paclitaxel, RT]]
 +
</div></div>
 +
===References===
 +
#'''LAMP:''' Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [https://doi.org/10.1200/jco.2005.55.405 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16087941 PubMed]
 +
#'''CTRT99/97:''' Huber RM, Flentje M, Schmidt M, Pöllinger B, Gosse H, Willner J, Ulm K; Bronchial Carcinoma Therapy Group. Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group. J Clin Oncol. 2006 Sep 20;24(27):4397-404. [https://doi.org/10.1200/JCO.2005.05.4163 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16983107 PubMed]
 +
#'''CALGB 39801:''' Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; [[Study_Groups#CALGB|CALGB]]. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. [https://doi.org/10.1200/JCO.2006.07.3569 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17404369 PubMed] NCT00003387
 +
#'''ECOG 3598:''' Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.9116 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22271472 PubMed] NCT00004859
 +
==Cisplatin & Vinblastine {{#subobject:6b4fa8|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:2433e7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJM199010043231403 Dillman et al. 1990 (CALGB 8433)]
 +
|1984-1987
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#No_induction|No]] induction
 +
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 +
|-
 +
|[https://academic.oup.com/jnci/article-abstract/87/3/198/932006 Sause et al. 1995 (RTOG 88-08)]
 +
|1989-1992
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#No_induction|No]] induction
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
−
|[https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ Curran et al. 2011 (RTOG 9410)]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|1994-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Complex_multipart_regimens#RTOG_9410|See link]]
 +
| style="background-color:#fc8d59" |[[Complex_multipart_regimens#RTOG_9410|See link]]
 
|-
 
|-
 
|}
 
|}
−
''Note: dose reductions for age greater than 65 years were not described in this publication. This is intended for low-risk patients (i.e., single site of disease less than 10 cm with normal LDH).''
+
''<sup>1</sup>Reported efficacy for CALGB 8433 is based on the 1996 update.''<br>
 +
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 29
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 10
+
*[[Vinblastine (Velban)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
'''5-week course'''
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 10
+
</div>
−
====CNS therapy, prophylaxis====
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Cytarabine (Ara-C)]] 50 mg IT on day 1
+
====Subsequent treatment====
−
*[[Methotrexate (MTX)]] 12 mg IT on day 1
+
*[[#Radiation_therapy_2|RT]] x 60 to 63 Gy
−
*[[Hydrocortisone (Cortef)]] 50 mg IT admixed with all chemotherapy
 
−
====Supportive therapy====
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 24 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> every 6 hours until methotrexate level undetectable
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 8, held for MTX, and restarted after clearance continuing until ANC greater than 1000/uL
 
−
'''3 cycles'''
 
 
</div></div>
 
</div></div>
−
 
 
===References===
 
===References===
−
# '''NCI 89-C-41:''' Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. [https://doi.org/10.1200/jco.1996.14.3.925 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8622041 PubMed]
+
#'''CALGB 8433:''' Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, Carey RW, Frei EF 3rd, Green MR. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990 Oct 4;323(14):940-5. [https://doi.org/10.1056/NEJM199010043231403 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2169587 PubMed]
−
# '''UKLG LY06:''' Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. [https://doi.org/10.1093/annonc/mdf253 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12181251 PubMed]
+
##'''Update:''' Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst. 1996 Sep 4;88(17):1210-5. [https://academic.oup.com/jnci/article/88/17/1210/911128 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8780630 PubMed]
−
# Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15160953 PubMed]
+
#'''RTOG 88-08:''' Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran WJ, Byhardt RW, Turrisi AT, Dar AR, Cox JD. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst. 1995 Feb 1;87(3):198-205. [https://academic.oup.com/jnci/article-abstract/87/3/198/932006 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7707407 PubMed]
−
# '''MRC/NCRI LY10:''' Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. [http://www.bloodjournal.org/content/112/6/2248.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102 PubMed]
+
##'''Update:''' Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A 3rd. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000 Feb;117(2):358-64. [https://journal.chestnet.org/article/S0012-3692(15)48622-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10669675 PubMed]
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007/s12185-010-0728-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21120644 PubMed]
+
#'''RTOG 9410:''' Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745 PubMed] NCT01134861
−
==CODOX-M/IVAC {{#subobject:ef0953|Regimen=1}}==
+
=Definitive therapy for locally advanced disease=
−
CODOX-M/IVAC: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+
==Carboplatin & Paclitaxel (CP) & RT {{#subobject:899399|Regimen=1}}==
 +
CP & RT: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
<br>PC & RT: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 2/40/60 {{#subobject:5d3a16|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.24.5050 Yamamoto et al. 2010 (WJTOG0105)]
 +
|2001-2005
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#MVP_.26_RT_88|MVP & RT]]<br> 2. [[#Carboplatin.2C_Irinotecan.2C_RT_88|Carboplatin, Irinotecan, RT]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 2 IV once per day on days 1, 8, 15, 22, 29, 36
 +
*[[Paclitaxel (Taxol)]] 40 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 60 Gy
 +
'''6-week course'''
 +
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #1, "Original Magrath" {{#subobject:17967a|Variant=1}}===
+
===Regimen variant #2, 2/45/60 {{#subobject:5d4d16|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902826/ Lu et al. 2010 (ID99-303)]
 +
|2000-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_AE-941.2C_RT_77|PC, AE-941, RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ Hoang et al. 2012 (ECOG 3598)]
 +
|2000-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Complex_multipart_regimens#ECOG_3598|See link]]
 +
| style="background-color:#ffffbf" |[[Complex_multipart_regimens#ECOG_3598|See link]]
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419359/ Bradley et al. 2015 (RTOG 0617)]
 +
| rowspan="2" |2007-2011
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Cetuximab.2C_RT_99|CP, Cetuximab, concurrent RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|CP & RT]]; high-dose RT<br> 3. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Cetuximab.2C_RT_99|CP, Cetuximab, RT]]; high-dose RT
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdx009 Liang et al. 2017]
 +
|2007-2011
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*ECOG 3598: [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|PC]] induction x 2
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 2 IV over 30 minutes once per day on days 1, 8, 15, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 1, 8, 15, '''given first'''
 +
'''21-day cycle for 2 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 2 Gy fractions x 30 fractions (total of 60 Gy)
 +
'''6-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*RTOG 0617: [[#Carboplatin_.26_Paclitaxel_.28CP.29_4|PC]] consolidation x 2
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 2/45/63 {{#subobject:59d765|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.1996.14.3.925 Magrath et al. 1996 (NCI 89-C-41)]
+
|[https://doi.org/10.1200/jco.2005.55.405 Belani et al. 2005 (LAMP)]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: This variant is intended for high-risk patients.''
+
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|PC]] induction
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, Part 1: CODOX-M====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Carboplatin (Paraplatin)]] AUC 2 IV over 30 minutes once per day on days 1, 8, 15, '''given second'''
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> IV once per day on days 1 & 8
+
*[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 1, 8, 15, '''given first'''
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
'''21-day cycle for 2 cycles'''
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
+
====Radiotherapy====
−
**65 years or younger: 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
+
*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 1.8 Gy fractions x 25 fractions, then 2 Gy fractions x 9 fractions
−
**Older than 65 years: 100 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 900 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 1000 mg/m<sup>2</sup>)
+
'''7-week course'''
−
====Supportive therapy====
+
</div>
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV Q3H, starting 36 hours after start of IV [[Methotrexate (MTX)]] until 48 hours, then every 6 hours until methotrexate level undetectable
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal [[Methotrexate (MTX)]]
+
====Subsequent treatment====
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
+
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_4|PC]] consolidation x 2
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
====Chemotherapy, Part 2: IVAC====
 
−
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 
−
**65 years or younger: 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
**Older than 65 years: 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**65 years or younger: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
**Older than 65 years: 1000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] by the following age-based criteria:
 
−
**65 or younger: 300 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 300 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
 
−
**Older than 65: 200 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 200 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal methotrexate
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
 
−
'''2 cycles each of CODOX-M and IVAC (alternating)'''
 
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #2 {{#subobject:3df4a3|Variant=1}}===
+
===Regimen variant #4, 2/50/66 {{#subobject:c54de8|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2006.07.3569 Vokes et al. 2007 (CALGB 39801)]
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_3|PC]] induction x 2 versus [[#No_induction|no induction]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, '''given first'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 66 Gy
 +
'''7-week course'''
 +
</div></div>
 +
===References===
 +
#'''LAMP:''' Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [https://doi.org/10.1200/jco.2005.55.405 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16087941 PubMed]
 +
#'''CALGB 39801:''' Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; [[Study_Groups#CALGB|CALGB]]. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. [https://doi.org/10.1200/JCO.2006.07.3569 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17404369 PubMed] NCT00003387
 +
#'''ID99-303:''' Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst. 2010 Jun 16;102(12):859-65. Epub 2010 May 26. [https://academic.oup.com/jnci/article/102/12/859/2568981 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902826/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20505152 PubMed] NCT00005838
 +
#'''WJTOG0105:''' Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. [https://doi.org/10.1200/JCO.2009.24.5050 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20625120 PubMed] NCT00144053
 +
##'''Update:''' Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Ymamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. [https://doi.org/10.1001/jamaoncol.2021.0113 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7974833/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33734289/ PubMed]
 +
#'''ECOG 3598:''' Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. [https://doi.org/10.1200/JCO.2011.36.9116 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295560/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22271472 PubMed] NCT00004859
 +
#'''RTOG 0617:''' Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. [https://doi.org/10.1016/s1470-2045(14)71207-0 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419359/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25601342 PubMed] NCT00533949
 +
##'''Update:''' Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. [https://doi.org/10.1200/jco.19.01162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048161/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31841363 PubMed]
 +
##'''Dataset:''' [https://data.projectdatasphere.org/projectdatasphere/html/content/361 Project Data Sphere]
 +
<!-- Note: This study was previously oral presented as: 15th World Conference on Lung Cancer, Sydney, 27–30 October 2013. -->
 +
#Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. [https://doi.org/10.1093/annonc/mdx009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28137739 PubMed] NCT01494558
 +
#'''ECOG E5181:''' NCT04092283
 +
#'''MS200647_0005:''' NCT03840902
 +
#'''PACIFIC 2:''' NCT03519971
 +
==Carboplatin, Vinorelbine, RT {{#subobject:c9edfa|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a0fcb6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776981/ Strøm et al. 2013 (Conrad)]
 +
|2006-2011
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Carboplatin_.26_Vinorelbine|Carboplatin & Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1
 +
*[[Vinorelbine (Navelbine)]] 60 mg/m<sup>2</sup> PO once per day on days 1 & 8
 +
'''21-day cycle for 4 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]] 42 Gy in 15 fractions
 +
</div></div>
 +
===References===
 +
#'''Conrad:''' Strøm HH, Bremnes RM, Sundstrøm SH, Helbekkmo N, Fløtten O, Aasebø U; Norwegian Lung Cancer Study Group. Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2013 Sep 17;109(6):1467-75. Epub 2013 Aug 20. [https://www.nature.com/articles/bjc2013466 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3776981/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23963145 PubMed] ISRCTN63778716
 +
==Carboplatin & RT {{#subobject:f563a8|Regimen=1}}==
 +
Carboplatin & RT: Carboplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:6b0bae|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdf253 Mead et al. 2002 (UKLG LY06)]
+
|[https://doi.org/10.1016/S1470-2045(12)70139-0 Atagi et al. 2012 (JCOG0301)]
−
|style="background-color:#91cf61"|Phase 2
+
|2003-2010
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Radiation_therapy_2|RT]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 
|-
 
|-
 
|}
 
|}
−
''Note: This variant is intended for high-risk patients; modifications to the original NCI 89-C-41 are only in the CODOX-M portion.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, Part 1: CODOX-M====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Carboplatin (Paraplatin)]] 30 mg/m<sup>2</sup> IV once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+
====Radiotherapy====
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
*Concurrent [[External_beam_radiotherapy|radiation therapy]]: 60 Gy, details not available in abstract
−
*[[Methotrexate (MTX)]] 1200 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 5520 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 6720 mg/m<sup>2</sup>)
+
</div></div>
−
====Supportive therapy====
+
===References===
−
*[[Folinic acid (Leucovorin)]] 192 mg/m<sup>2</sup> IV once at 36 hours after start of IV methotrexate, then 12 mg/m<sup>2</sup> IV every 6 hours until MTX level less than 0.05
+
#'''JCOG0301:''' Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; [[Study_Groups#JCOG|JCOG]] Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. [https://doi.org/10.1016/S1470-2045(12)70139-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22622008 PubMed] NCT00132665
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
+
==Cisplatin & RT {{#subobject:e6b41e|Regimen=1}}==
−
====CNS therapy, prophylaxis====
+
Cisplatin & RT: Cisplatin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
+
<div class="toccolours" style="background-color:#eeeeee">
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
+
===Regimen variant #1 {{#subobject:6b0bae|Variant=1}}===
−
====Chemotherapy, Part 2: IVAC====
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
+
!style="width: 20%"|Study
−
**Age 65 years or younger: 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
!style="width: 20%"|Years of enrollment
−
**Age older than 65 years: 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
!style="width: 20%"|Comparator
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
**65 or younger: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
+
|-
−
**Older than 65: 1000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+
| rowspan="2" |[https://doi.org/10.1056/NEJM199202203260805 Schaake-Koning et al. 1992]
−
====Supportive therapy====
+
|rowspan=2|1984-1989
−
*[[Mesna (Mesnex)]] by the following age-based criteria:
+
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
−
**65 years or younger: 300 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 300 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
+
|1. [[#Cisplatin_.26_RT|Cisplatin & RT]]; weekly cisplatin
−
**Older than 65 years: 200 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 200 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal methotrexate
+
|-
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
+
|2. [[#Radiation_therapy_2|RT]]
−
====CNS therapy, prophylaxis====
+
| style="background-color:#1a9850" |Superior OS
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
+
|-
−
'''2 cycles each of CODOX-M and IVAC (alternating)'''
+
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 6 mg/m<sup>2</sup> IV once per day on days of radiation
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows:
 +
**Weeks 1 & 2: 3 Gy fractions, five fractions per week
 +
**Weeks 3 to 5: no radiation
 +
**Weeks 6 & 7: 2.5 Gy fractions, five fractions per week
 +
'''7-week course'''
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol variant #3, "Modified Magrath" {{#subobject:5382df|Variant=1}}===
+
===Regimen variant #2 {{#subobject:6byg71|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004]
+
|[https://doi.org/10.1200/jco.1995.13.6.1425 Blanke et al. 1995]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts
+
|1986-1992
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Radiation_therapy_2|RT]]
 +
| style="background-color:#d9ef8b" |Might have superior PFS
 
|-
 
|-
 
|}
 
|}
−
''Note: All modifications are in Part 1: CODOX-M. Also note that dose reductions for age greater than 65 years were not described in this publication. This is intended for high-risk patients.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, Part 1: CODOX-M====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 10
+
'''21-day cycle for 3 cycles'''
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
====Radiotherapy====
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 10
+
*Concurrent [[External_beam_radiotherapy|radiation therapy]] 60 to 65 Gy total tumor dose in daily fractions of 1.8 to 2 Gy
−
====CNS therapy, prophylaxis====
+
'''6-week course'''
−
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1 & 3
+
</div></div>
−
*[[Methotrexate (MTX)]] 12 mg IT on day 1
+
===References===
−
*[[Hydrocortisone (Cortef)]] 50 mg IT admixed with all chemotherapy
+
#Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, Renaud A, Rodrigus P, Schuster-Uitterhoeve L, Sculier JP, van Zandwijk N, Bartelink H. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992 Feb 20;326(8):524-30. [https://doi.org/10.1056/NEJM199202203260805 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1310160 PubMed]
−
====Supportive therapy====
+
#Blanke C, Ansari R, Mantravadi R, Gonin R, Tokars R, Fisher W, Pennington K, O'Connor T, Rynard S, Miller M, Einhorn L. Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol. J Clin Oncol. 1995 Jun;13(6):1425-9. [https://doi.org/10.1200/jco.1995.13.6.1425 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7751888/ PubMed]
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 24 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> every 6 hours until methotrexate level undetectable
+
==Cisplatin, Docetaxel, RT {{#subobject:6d901b|Regimen=1}}==
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 3 to 8, held for MTX, and restarted after clearance continuing until ANC greater than 1000/uL
+
DC & RT: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
−
====Chemotherapy, Part 2: IVAC====
+
<br>DP & RT: '''<u>D</u>'''ocetaxel, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
<div class="toccolours" style="background-color:#eeeeee">
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
===Regimen variant #1, 20/20 {{#subobject:fdef61|Variant=1}}===
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
====CNS therapy, prophylaxis====
+
!style="width: 20%"|Study
−
*[[Methotrexate (MTX)]] 12 mg IT on day 5, admixed with [[Hydrocortisone (Cortef)]]
+
!style="width: 20%"|Years of enrollment
−
*[[Hydrocortisone (Cortef)]] 50 mg IT on day 5, admixed with [[Methotrexate (MTX)]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
−
====Supportive therapy====
+
!style="width: 20%"|Comparator
−
*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 300 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
+
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 6 and continuing until ANC greater than 1000/uL
+
|-
−
'''2 cycles each of CODOX-M and IVAC (alternating)'''
+
|[https://doi.org/10.1007/s00280-013-2308-5 Oh et al. 2013 (KASLC 0401)]
 +
|2005-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin.2C_Paclitaxel.2C_RT_99|TP & RT]]<br> 2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_RT_99|GC & RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|[https://doi.org/10.1200/JCO.2014.60.0130 Ahn et al. 2015 (KCSG-LU05-04)]
 +
|2005-2011
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
''In KCSG-LU05-04, no benefit was observed to giving post-definitive consolidation.''
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 +
*[[Docetaxel (Taxotere)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2 Gy fractions x 33 fractions (total dose: 66 Gy)
 +
'''6-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*KCSG-LU05-04: [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]] consolidation versus [[Non-small_cell_lung_cancer_-_null_regimens#Observation_2|no further treatment]]
 
</div></div><br>
 
</div></div><br>
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
 
+
===Regimen variant #2, 40/40 {{#subobject:6a7064|Variant=1}}===
−
===Protocol variant #4 {{#subobject:d0f19a|Variant=1}}===
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
!style="width: 20%"|Study
−
!style="width: 25%"|Study
+
!style="width: 20%"|Years of enrollment
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ Mead et al. 2008 (MRC/NCRI LY10)]
+
|[https://doi.org/10.1200/JCO.2009.24.7577 Segawa et al. 2010 (OLCSG 0007)]
−
|style="background-color:#91cf61"|Phase 2
+
|2000-2005
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#MVP_.26_RT_88|MVP & RT]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 
|-
 
|-
 
|}
 
|}
−
''Note: This variant is intended for high-risk patients; modifications to the UKLG LY06 protocol are only in the CODOX-M portion.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, Part 1: CODOX-M====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 8
+
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
+
'''28-day cycle for 2 cycles'''
−
*[[Methotrexate (MTX)]] 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
+
====Radiotherapy====
−
====Supportive therapy====
+
*Concurrent [[External_beam_radiotherapy|radiation therapy]]
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> IV once at 36 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> IV every 3 hours between hours 36 and 48, then 15 mg/m<sup>2</sup> IV every 6 hours until MTX level less than 0.05
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 13 and continuing until ANC greater than 1000/uL
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
====Chemotherapy, Part 2: IVAC====
 
−
*[[Ifosfamide (Ifex)]] by the following age-based criteria:
 
−
**65 years or younger: 1500 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
**Older than 65 years: 1000 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**65 or younger: 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
**Older than 65: 1000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Mesna (Mesnex)]] by the following age-based criteria:
 
−
**65 years or younger: 300 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 300 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
 
−
**Older than 65 years: 200 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 200 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO once 24 hours after intrathecal methotrexate
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 7 and continuing until ANC greater than 1000/uL
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
 
−
'''2 cycles each of CODOX-M and IVAC (alternating)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NCI 89-C-41:''' Magrath I, Adde M, Shad A, Venzon D, Seibel N, Gootenberg J, Neely J, Arndt C, Nieder M, Jaffe E, Wittes RA, Horak ID. Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen. J Clin Oncol. 1996 Mar;14(3):925-34. [https://doi.org/10.1200/jco.1996.14.3.925 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8622041 PubMed]
+
#'''OLCSG 0007:''' Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, Kanazawa S, Takata I, Nogami N, Hotta K, Hiraki A, Tabata M, Matsuo K, Tanimoto M. Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010 Jul 10;28(20):3299-306. Epub 2010 Jun 7. [https://doi.org/10.1200/JCO.2009.24.7577 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20530281 PubMed] UMIN000000085
−
# '''UKLG LY06:''' Mead GM, Sydes MR, Walewski J, Grigg A, Hatton CS, Pescosta N, Guarnaccia C, Lewis MS, McKendrick J, Stenning SP, Wright D; UKLG LY06 collaborators. An international evaluation of CODOX-M and CODOX-M alternating with IVAC in adult Burkitt's lymphoma: results of United Kingdom Lymphoma Group LY06 study. Ann Oncol. 2002 Aug;13(8):1264-74. Erratum in: Ann Oncol. 2002 Dec;13(12):1961. Norbert, P [corrected to Pescosta, N]. [https://doi.org/10.1093/annonc/mdf253 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12181251 PubMed]
+
#'''KASLC 0401:''' Oh IJ, Kim KS, Kim YC, Ban HJ, Kwon YS, Kim YI, Lim SC, Chung WK, Nam TK, Song JY, Yoon MS, Ahn SJ. A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. Cancer Chemother Pharmacol. 2013 Dec;72(6):1247-54. Epub 2013 Oct 5. [https://doi.org/10.1007/s00280-013-2308-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24091849 PubMed]
−
# Lacasce A, Howard O, Lib S, Fisher D, Weng A, Neuberg D, Shipp M. Modified Magrath regimens for adults with Burkitt and Burkitt-like lymphomas: preserved efficacy with decreased toxicity. Leuk Lymphoma. 2004 Apr;45(4):761-7. [https://doi.org/10.1080/1042819031000141301 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15160953 PubMed]
+
#'''KCSG-LU05-04:''' Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol. 2015 Aug 20;33(24):2660-6. Epub 2015 Jul 6. [https://doi.org/10.1200/JCO.2014.60.0130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26150444 PubMed] NCT00326378
−
# '''MRC/NCRI LY10:''' Mead GM, Barrans SL, Qian W, Walewski J, Radford JA, Wolf M, Clawson SM, Stenning SP, Yule CL, Jack AS; UK National Cancer Research Institute Lymphoma Clinical Studies Group; Australasian Leukaemia and Lymphoma Group. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial). Blood. 2008 Sep 15;112(6):2248-60. Epub 2008 Jul 8. [http://www.bloodjournal.org/content/112/6/2248.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532802/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18612102 PubMed]
+
==Cisplatin, Etoposide, RT {{#subobject:743aa8|Regimen=1}}==
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007/s12185-010-0728-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21120644 PubMed]
+
EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
−
==COPAD {{#subobject:cc6dc7|Regimen=1}}==
 
−
COPAD: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>AD</u>'''riamycin (Doxorubicin)
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:862ad5|Variant=1}}===
+
===Regimen variant #1, 45 Gy with response-adapted treatment {{#subobject:dcb6c1|Variant=1}}===
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
 
!style="width: 33%"|Study
 
!style="width: 33%"|Study
Line 490: Line 1,490:
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://doi.org/10.1200/jco.2002.03.055 Albain et al. 2002 (SWOG 9019)]
−
|1996-2001
+
|1992-1995
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407808/ Albain et al. 2009 (RTOG 93-09)]
 +
|1994-2001
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
'''28-day cycle for 2 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), to start within 24 hours of cycle 1 day 1
 +
'''5-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*SWOG 9019: Patients were re-imaged with CT scan (bone scan and head imaging were only done if patients had new symptoms), and those without progression or new metastatic disease received an additional 2 Gy per day x 8 fractions for a total of 61 Gy administered overall
 +
*RTOG 93-09: Additional radiation to 61 Gy, then [[#Cisplatin_.26_Etoposide_.28EP.29_3|cisplatin & etoposide]] consolidation versus surgery, then [[#Cisplatin_.26_Etoposide_.28EP.29_3|cisplatin & etoposide]] consolidation
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 60 to 66 Gy {{#subobject:426dfc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.14.4824 Kelly et al. 2008 (SWOG S0023)]
 +
|2001-2005
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1200/JCO.2008.17.7840 Hanna et al. 2008 (HOG Lun 01-24)]
 +
|2002-2006
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdx009 Liang et al. 2017]
 +
|2007-2011
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|PC & RT]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Eligibility criteria====
+
====Chemotherapy====
−
*Group A (completely resected stage I or abdominal stage II disease)
+
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
'''28-day cycle for 2 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.8 to 2 Gy fractions x 30 to 33 fractions (total dose: 60 to 66 Gy)
 +
'''6- to 6.5-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*SWOG S0023: [[#Docetaxel_monotherapy_88|Docetaxel]] x 3, then [[#Gefitinib_monotherapy_99|gefitinib]] versus [[Non-small_cell_lung_cancer_-_null_regimens#Placebo|placebo]]
 +
*HOG Lun 01-24: [[#Docetaxel_monotherapy_88|Docetaxel]] consolidation versus [[Non-small_cell_lung_cancer_-_null_regimens#Observation_2|observation]]
 +
*Liang et al. 2017: Optional consolidation chemotherapy
 +
*MS200647_0005: [[#Durvalumab_monotherapy|Durvalumab]] consolidation
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 66 Gy, split cisplatin {{#subobject:f35aaa|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.03.070 Fournel et al. 2005 (NPC 95-01)]
 +
|1996-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]], then [[#Radiation_therapy_2|RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> IV once per day on days 1 to 5
 +
'''28-day cycle for 2 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2 Gy fractions x 33 fractions (total dose: 66 Gy)
 +
'''6.5-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]] consolidation
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 69.6 Gy (hyperfractionated) {{#subobject:3ea5c6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ Curran et al. 2011 (RTOG 9410)]
 +
|rowspan=2|1994-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Cisplatin.2C_Vinblastine.2C_RT|Cisplatin, Vinblastine, RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]], then [[#Radiation_therapy_2|RT]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Etoposide (Vepesid)]] 50 mg PO twice per day on days 1 to 5, 8 to 12
 +
'''28-day cycle for 2 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.2 Gy fractions (total dose: 69.6 Gy), given twice per day for 5 days per week, starting on cycle 1 day 1
 +
</div></div>
 +
===References===
 +
#'''SWOG 9019:''' Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. [https://doi.org/10.1200/jco.2002.03.055 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12177106 PubMed]
 +
#Schild SE, Stella PJ, Geyer SM, Bonner JA, Marks RS, McGinnis WL, Goetz SP, Kuross SA, Mailliard JA, Kugler JW, Schaefer PL, Jett JR. Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):370-8. [https://doi.org/10.1016/s0360-3016(02)02930-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12243810/ PubMed]
 +
#'''NPC 95-01:''' Fournel P, Robinet G, Thomas P, Souquet PJ, Léna H, Vergnenégre A, Delhoume JY, Le Treut J, Silvani JA, Dansin E, Bozonnat MC, Daurés JP, Mornex F, Pérol M; Groupe Lyon-Saint-Etienne d'Oncologie Thoracique; Groupe Français de Pneumo-Cancérologie. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol. 2005 Sep 1;23(25):5910-7. Epub 2005 Aug 8. [https://doi.org/10.1200/JCO.2005.03.070 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16087956/ PubMed]
 +
#'''SWOG S0023:''' Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, Lau DH, Crowley JJ, Gandara DR. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008 May 20;26(15):2450-6. Epub 2008 Mar 31. [https://doi.org/10.1200/JCO.2007.14.4824 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18378568 PubMed] NCT00020709
 +
#'''HOG Lun 01-24:''' Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008 Dec 10;26(35):5755-60. Epub 2008 Nov 10. [https://doi.org/10.1200/JCO.2008.17.7840 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19001323 PubMed] NCT00216125
 +
#'''RTOG 93-09:''' Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009 Aug 1;374(9687):379-86. Epub 2009 Jul 24. [https://doi.org/10.1016/S0140-6736(09)60737-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407808/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19632716 PubMed] NCT00002550
 +
#'''RTOG 9410:''' Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745 PubMed] NCT01134861
 +
#Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. [https://doi.org/10.1093/annonc/mdx009 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28137739 PubMed] NCT01494558
 +
#'''MS200647_0005:''' NCT03840902
 +
#'''PACIFIC 2:''' NCT03519971
 +
==Cisplatin, Pemetrexed, RT {{#subobject:74ugg8|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:42ugzc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (MS200647_0005)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bintrafusp_alfa.2C_RT_77|CP, Bintrafusp alfa, RT]]<br>2. [[#Cisplatin.2C_Pemetrexed.2C_Bintrafusp_alfa.2C_RT_77|Cisplatin, Pemetrexed, Bintrafusp alfa, RT]]<br>3. [[#Cisplatin.2C_Etoposide.2C_Bintrafusp_alfa.2C_RT_77|EP, Bintrafusp alfa, RT]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 3 cycles'''
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|IMRT]], 2 Gy fractions x 30 (total dose: 60 Gy)
 +
'''6-week course'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[#Durvalumab_monotherapy|Durvalumab]] consolidation
 +
</div></div>
 +
===References===
 +
#'''MS200647_0005:''' '''contains dosing details on CT.gov''' NCT03840902
 +
==Cisplatin, Vinblastine, RT {{#subobject:54c5c4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c057fe|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ Curran et al. 2011 (RTOG 9410)]
 +
|rowspan=2|1994-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]], then [[#Radiation_therapy_2|RT]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once per day on days 1 & 29
 +
*[[Vinblastine (Velban)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
 +
====Radiotherapy====
 +
*Concurrent [[External_beam_radiotherapy|radiation therapy]]
 +
'''5-week course'''
 +
</div></div>
 +
===References===
 +
#'''RTOG 9410:''' Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745 PubMed] NCT01134861
 +
==Cisplatin, Vinorelbine, RT {{#subobject:59gcc4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c8ygfe|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2015.62.6812 Eberhardt et al. 2015 (ESPATUE)]
 +
|2004-2013
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|Surgery
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Cisplatin_.26_Paclitaxel_88|Cisplatin & Paclitaxel]] induction
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV twice per day on days 2 to 4 (total dose per cycle: 1500 mg/m<sup>2</sup>)
+
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 2 & 9
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 6
+
*[[Vinorelbine (Navelbine)]] 20 mg/m<sup>2</sup> IV once per day on days 2 & 9
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
+
====Radiotherapy====
−
====Glucocorticoid therapy====
+
*Concurrent [[External_beam_radiotherapy|radiation therapy]] 1.5 Gy twice per day for 30 fractions (45 Gy total)
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 6
+
'''21-day course'''
−
'''3 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 10<sup>9</sup>/L'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''ESPATUE:''' Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V, Welter S, Budach W, Spengler W, Kimmich M, Fischer B, Schmidberger H, De Ruysscher D, Belka C, Cordes S, Hepp R, Lütke-Brintrup D, Lehmann N, Schuler M, Jöckel KH, Stamatis G, Stuschke M. Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE). J Clin Oncol. 2015 Dec 10;33(35):4194-201. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.62.6812 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26527789 PubMed]
−
==COPADM {{#subobject:841673|Regimen=1}}==
+
==Radiation therapy {{#subobject:6a90fb|Regimen=1}}==
−
COPADM: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>AD</u>'''riamycin (Doxorubicin), '''<u>M</u>'''ethotrexate
+
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:39dc15|Variant=1}}===
+
===Regimen variant #1, 20 Gy {{#subobject:1g2326|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 521: Line 1,729:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063335/ Ball et al. 1997]
−
|1996-2001
+
|1988-1993
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|style="background-color:#d3d3d3"|
+
|[[#Fluorouracil_.26_RT_88|5-FU & RT]]
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(15)01317-3 Ribrag et al. 2016 (LMBA-02)]
+
|}
−
|2004-2010
+
<div class="toccolours" style="background-color:#b3e2cd">
−
|style="background-color:#1a9851"|Phase 3 (C)
+
====Radiotherapy====
−
|[[#R-COPADM|R-COPADM]]
+
*[[External beam radiotherapy]] 4 Gy in 5 fractions (20 Gy total)
−
|style="background-color:#fc8d59"|Seems to have inferior EFS
+
'''5-day course'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 45 Gy + 18 Gy boost (63 Gy total) {{#subobject:5d7861|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ Curran et al. 2011 (RTOG 9410)]
 +
|1994-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Complex_multipart_regimens#RTOG_9410|See link]]
 +
|[[Complex_multipart_regimens#RTOG_9410|See link]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.55.405 Belani et al. 2005 (LAMP)]
 +
|1998-2001
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
 
|}
 
|}
−
''Note: This protocol is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement) or group C (CNS and/or bone marrow involvement). Diviné et al. 2005 list the dose of HD-MTX as 3 mg/m<sup>2</sup> but this is presumed to be a typo.''
 
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#CVP|COP prephase]]
+
*LAMP: [[#Carboplatin_.26_Paclitaxel_.28CP.29_3|Carboplatin & Paclitaxel]] x 2
 +
*RTOG 9410: [[#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]] x 5 wk
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, COPADM #1====
+
====Radiotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 250 mg/m<sup>2</sup> IV twice per day on days 2 to 4 (total dose: 1500 mg/m<sup>2</sup>)
+
*[[External beam radiotherapy]] 45 Gy in 1.8 Gy fractions x 25 fractions, then 18 Gy boost in 2 Gy fractions x 9 fractions
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
'''7-week course'''
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
+
</div></div><br>
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
+
<div class="toccolours" style="background-color:#eeeeee">
−
====Glucocorticoid therapy====
+
===Regimen variant #3, 60 Gy {{#subobject:12f326|Variant=1}}===
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 6
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
====Supportive therapy====
+
! style="width: 20%" |Study
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours on days 2 to 4
+
! style="width: 20%" |Years of enrollment
−
====CNS therapy, prophylaxis (group B)====
+
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 2 & 6
+
! style="width: 20%" |Comparator
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)
+
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
−
====CNS therapy, treatment (group C)====
+
|-
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 2, 4, 6
+
|[https://doi.org/10.1016/0360-3016(88)90229-5 Perez et al. 1988]
−
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 2, 4, 6
+
|NR
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)
+
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Levamisole_.26_RT_99|Levamisole & RT]]
 +
| style="background-color:#ffffbf" |Did not meet endpoint of OS
 +
|-
 +
|[https://annals.org/aim/article-abstract/705110/thoracic-radiation-therapy-alone-compared-combined-chemoradiotherapy-locally-unresectable-non Morton et al. 1991]
 +
|1983-1987
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#MACC_.26_RT_99|MACC & RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.1.4 Clamon et al. 1999 (CALGB 9130)]
 +
|1991-NR
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_RT|Carboplatin & RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1016/S0360-3016(01)02797-3 Bradley et al. 2002 (RTOG 93-04)]
 +
|1994-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Interferon_beta_.26_RT_99|Beta-interferon & RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdh100 Groen et al. 2004]
 +
|1995-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_RT|Carboplatin & RT]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS24
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(12)70139-0 Atagi et al. 2012 (JCOG0301)]
 +
|2003-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_RT|Carboplatin & RT]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*CALGB 9130: [[#Cisplatin_.26_Vinblastine_2|Cisplatin & Vinblastine]] x 5 wk
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Radiotherapy====
 +
*[[External beam radiotherapy]] 60 Gy
 
'''One course'''
 
'''One course'''
−
''As soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 10<sup>9</sup>/L, patients proceeded to:''
+
</div></div>
−
====Chemotherapy, COPADM #2====
+
===References===
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV twice per day on days 2 to 4 (total dose: 3000 mg/m<sup>2</sup>)
+
#Perez CA, Bauer M, Emami BN, Byhardt R, Brady LW, Doggett RL, Gardner P, Zinninger M. Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG. Int J Radiat Oncol Biol Phys. 1988 Dec;15(6):1337-46. [https://doi.org/10.1016/0360-3016(88)90229-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2848786/ PubMed]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 6
+
#Morton RF, Jett JR, McGinnis WL, Earle JD, Therneau TM, Krook JE, Elliott TE, Mailliard JA, Nelimark RA, Maksymiuk AW, Drummond RG, Laurie JA, Kugler JW, Anderson RT. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer: a randomized, phase III trial. Ann Intern Med. 1991 Nov 1;115(9):681-6. [https://annals.org/aim/article-abstract/705110/thoracic-radiation-therapy-alone-compared-combined-chemoradiotherapy-locally-unresectable-non link to original article] [https://pubmed.ncbi.nlm.nih.gov/1656827 PubMed]
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
+
#Ball D, Smith J, Bishop J, Olver I, Davis S, O'Brien P, Bernshaw D, Ryan G, Millward M. A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer. Br J Cancer. 1997;75(5):690-7. [https://doi.org/10.1038/bjc.1997.123 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063335/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9043026 PubMed]
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
+
#'''CALGB 9130:''' Clamon G, Herndon J, Cooper R, Chang AY, Rosenman J, Green MR; [[Study_Groups#CALGB|CALGB]]; [[Study_Groups#ECOG|ECOG]]. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol. 1999 Jan;17(1):4-11. [https://doi.org/10.1200/JCO.1999.17.1.4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10458211 PubMed]
−
====Glucocorticoid therapy====
+
#'''RTOG 93-04:''' Bradley JD, Scott CB, Paris KJ, Demas WF, Machtay M, Komaki R, Movsas B, Rubin P, Sause WT. A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04). Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1173-9. [https://doi.org/10.1016/S0360-3016(01)02797-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11955727 PubMed]
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 6
+
#Groen HJ, van der Leest AH, Fokkema E, Timmer PR, Nossent GD, Smit WJ, Nabers J, Hoekstra HJ, Hermans J, Otter R, van Putten JW, de Vries EG, Mulder NH. Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study. Ann Oncol. 2004 Mar;15(3):427-32. [https://doi.org/10.1093/annonc/mdh100 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14998844 PubMed]
 +
#'''LAMP:''' Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [https://doi.org/10.1200/jco.2005.55.405 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16087941 PubMed]
 +
#'''RTOG 9410:''' Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21903745 PubMed] NCT01134861
 +
#'''JCOG0301:''' Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; [[Study_Groups#JCOG|JCOG]] Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. [https://doi.org/10.1016/S1470-2045(12)70139-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22622008 PubMed] NCT00132665
 +
#'''SWOG S1914:''' NCT04214262
 +
=Consolidation or maintenance after definitive therapy for inoperable disease=
 +
==Carboplatin & Paclitaxel (CP) {{#subobject:81d5a7|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:d729a8|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
! style="width: 33%" |Study
 +
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.55.405 Belani et al. 2005 (LAMP)]
 +
|1998-2001
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419359/ Bradley et al. 2015 (RTOG 0617)]
 +
|2007-2011
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_RT|Carboplatin, Paclitaxel, RT]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 30 minutes once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''21-day cycle for 2 cycles'''
 +
</div></div>
 +
===References===
 +
#'''LAMP:''' Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [https://doi.org/10.1200/jco.2005.55.405 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16087941 PubMed]
 +
#'''RTOG 0617:''' Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. [https://doi.org/10.1016/s1470-2045(14)71207-0 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419359/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25601342 PubMed] NCT00533949
 +
##'''Update:''' Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. [https://doi.org/10.1200/jco.19.01162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048161/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31841363 PubMed]
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/272 Project Data Sphere]
 +
==Durvalumab monotherapy {{#subobject:6f72e5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:04242b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1709937 Antonia et al. 2017 (PACIFIC)]
 +
|2014-2016
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo_2|Placebo]]
 +
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 47.5 vs 29.1 mo <br>(HR 0.72, 95% CI 0.59-0.89)
 +
|-
 +
|Awaiting publication (CheckMate 73L)
 +
|2019-2025
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Ipilimumab_.26_Nivolumab_66|Ipilimumab & Nivolumab]]<br>2. [[#Nivolumab_monotherapy_66|Nivolumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|Awaiting publication (SKYSCRAPER-03)
 +
|2020-2024
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Atezolizumab_.26_Tiragolumab_77|Atezolizumab & Tiragolumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|Awaiting publication (KEYLYNK-012)
 +
|2020-2026
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Olaparib_.26_Pembrolizumab_66|Olaparib & Pembrolizumab]]<br>2. [[#Pembrolizumab_monotherapy_66|Pembrolizumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|Awaiting publication (BGB-A317-A1217-301)
 +
|2021-2025
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Ociperlimab_.26_Tislelizumab_77|Ociperlimab & Tislelizumab]]<br>2. [[#Tislelizumab_monotherapy_66|Tislelizumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|Awaiting publication (PACIFIC-9)
 +
|2022-2026
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Durvalumab_.26_Monalizumab_77|Durvalumab & Monalizumab]]<br>2. [[#Durvalumab_.26_Oleclumab_77|Durvalumab & Oleclumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|Awaiting publication (PACIFIC-8)
 +
|2022-2027
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Domvanalimab_.26_Durvalumab_77|Domvanalimab & Durvalumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2022 update.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*PACIFIC: "Two or more cycles (defined according to local practice) of platinum-based chemotherapy (containing etoposide, vinblastine, vinorelbine, a taxane [paclitaxel or docetaxel], or pemetrexed) concurrently with definitive radiation therapy (54 to 66 Gy), in which the mean dose to the lung was less than 20 Gy, the V20 (the volume of lung parenchyma that received 20 Gy or more) was less than 35%, or both."
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Durvalumab (Imfinzi)]] 10 mg/kg IV once on day 1
 +
'''14-day cycle for up to 26 cycles (1 year)'''
 +
</div></div>
 +
===References===
 +
#'''PACIFIC:''' Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. Epub 2017 Sep 8. [https://doi.org/10.1056/NEJMoa1709937 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28885881 PubMed] NCT02125461
 +
##'''Update:''' Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. Epub 2018 Sep 25. [https://doi.org/10.1056/nejmoa1809697 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30280658 PubMed]
 +
##'''Update:''' Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Özgüroğlu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. Epub 2019 Oct 14. [https://doi.org/10.1016/j.jtho.2019.10.002 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7244187/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31622733 PubMed]
 +
##'''Update:''' Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Özgüroğlu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. Epub 2021 Jan 19. [https://doi.org/10.1016/j.jtho.2020.12.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33476803/ PubMed]
 +
##'''Update:''' Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. Epub 2022 Feb 2. [https://doi.org/10.1200/jco.21.01308 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9015199/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35108059/ PubMed]
 +
#'''BGB-A317-A1217-301:''' NCT04866017
 +
#'''CheckMate 73L:''' NCT04026412
 +
#'''KEYLYNK-012:''' NCT04380636
 +
#'''PACIFIC-8:''' NCT05211895
 +
#'''PACIFIC-9:''' NCT05221840
 +
#'''SKYSCRAPER-03:''' NCT04513925
 +
==Sugemalimab monotherapy {{#subobject:8ibxe5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1j242b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/s1470-2045(21)00630-6 Zhou et al. 2022 (GEMSTONE-301)]
 +
|2018-2020
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo_2|Placebo]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 9 vs 5.8 mo<br>(HR 0.64, 95% CI 0.48-0.85)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Concurrent or sequential chemoradiotherapy
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Sugemalimab (Cejemly)]] 1200 mg IV once on day 1
 +
'''21-day cycle for up to 35 cycles (2 years)'''
 +
</div></div>
 +
===References===
 +
#'''GEMSTONE-301:''' Zhou Q, Chen M, Jiang O, Pan Y, Hu D, Lin Q, Wu G, Cui J, Chang J, Cheng Y, Huang C, Liu A, Yang N, Gong Y, Zhu C, Ma Z, Fang J, Chen G, Zhao J, Shi A, Lin Y, Li G, Liu Y, Wang D, Wu R, Xu X, Shi J, Liu Z, Cui N, Wang J, Wang Q, Zhang R, Yang J, Wu YL. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-219. Epub 2022 Jan 14. [https://doi.org/10.1016/s1470-2045(21)00630-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35038429/ PubMed] NCT03728556
 +
=Advanced or metastatic disease, first-line=
 +
==Atezolizumab monotherapy {{#subobject:ns5fc4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:ahvnjf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (SKYSCRAPER-01)
 +
|2020-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Atezolizumab_.26_Tiragolumab_77|Atezolizumab & Tiragolumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm, in this context.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''SKYSCRAPER-01:''' NCT04294810
 +
==Carboplatin & Docetaxel {{#subobject:bdce59|Regimen=1}}==
 +
DCb: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''ar'''<u>b</u>'''oplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:bce236|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2003.12.046 Fossella et al. 2003 (TAX 326)]
 +
| rowspan="2" |1998-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdl078 Booton et al. 2006 (BTOG1)]
 +
|2001-2002
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[Non-small_cell_lung_cancer_-_historical#MIC_3|MIC]]<br> 2. [[Non-small_cell_lung_cancer_-_historical#MVP_.28Vinblastine.29|MVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.35.5214 Groen et al. 2011 (NVALT-4)]
 +
|2003-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Celecoxib_99|DCb & Celecoxib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.21.9618 Lynch et al. 2010 (BMS099)]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Docetaxel_.28DCb.29_.26_Cetuximab_99|DCb & Cetuximab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for up to 5 cycles (NVALT-4), 6 cycles (BMS099), or indefinitely'''
 +
</div></div>
 +
===References===
 +
<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
 +
#'''TAX 326:''' Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [https://doi.org/10.1200/jco.2003.12.046 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12837811 PubMed]
 +
#'''BTOG1:''' Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. [https://doi.org/10.1093/annonc/mdl078 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16603599 PubMed]
 +
#'''BMS099:''' Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. [https://doi.org/10.1200/JCO.2009.21.9618 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20100966 PubMed] NCT00112294
 +
<!-- Presented in part at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL. -->
 +
#'''NVALT-4:''' Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, Dalesio O, Biesma B, Smit HJ, Termeer A, Hiltermann TJ, van den Borne BE, Schramel FM. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol. 2011 Nov 10;29(32):4320-6. Epub 2011 Oct 11. [https://doi.org/10.1200/JCO.2011.35.5214 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21990410 PubMed] NTR1703
 +
==Carboplatin & Etoposide (CE) {{#subobject:4c2ff5|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f920ac|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1990.8.9.1556 Klastersky et al. 1990 (EORTC 07861)]
 +
|1987-1989
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]]
 +
| style="background-color:#fee08b" |Might have inferior ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] 325 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
'''3- to 4-week cycles'''
 +
</div></div>
 +
===References===
 +
#'''EORTC 07861:''' Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. [https://doi.org/10.1200/JCO.1990.8.9.1556 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2167953 PubMed]
 +
==Carboplatin & Gemcitabine (GCb) {{#subobject:8669e|Regimen=1}}==
 +
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''arboplatin
 +
<br>GCa: '''<u>G</u>'''emcitabine & '''<u>Ca</u>'''rboplatin
 +
<br>GCb: '''<u>G</u>'''emcitabine & '''<u>C</u>'''ar'''<u>b</u>'''oplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 4/1000 {{#subobject:fa3601|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360329/ Helbekkmo et al. 2007]
 +
|2003-2004
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Vinorelbine|VCb]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: AUC was calculated using the Chatelut formula.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 4 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 +
'''21-day cycle for 3 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 5/1000 q3wk {{#subobject:cfb199|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2008.20.9114 Grønberg et al. 2009]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 5/1000 q4wk {{#subobject:82e4e7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1002/cncr.11535 Danson et al. 2003]
 +
|1997-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[Non-small_cell_lung_cancer_-_historical#MIC_3|MIC]]<br> 2. [[Non-small_cell_lung_cancer_-_historical#MVP_.28Vinblastine.29|MVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 5/1200 {{#subobject:58b47e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(03)00233-2 Zatloukal et al. 2003]
 +
|1999-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of grade 3/4 toxicity
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.03.037 Rudd et al. 2005]
 +
|1999-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer_-_historical#MIC_3|MIC]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 5/1250 q3wk {{#subobject:4bca29|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.01.2781 Sederholm et al. 2005]
 +
|1998-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691357/ Bepler et al. 2013 (MCC-15005)]
 +
|2007-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|ERCC1 and RRM1 expression-based chemotherapy
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS6
 +
|
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #6, 5/1250 q4wk {{#subobject:7e79d9|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70254-7 Wu et al. 2013 (FASTACT-2)]
 +
|2009-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer,_EGFR-mutated#Carboplatin_.26_Gemcitabine_.28GCb.29.2FErlotinib|Carboplatin & Gemcitabine/Erlotinib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|}
 +
''Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''28-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #7, 6/1000 {{#subobject:c7aefa|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdm430 Kosmidis et al. 2007]
 +
|2000-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Paclitaxel|Gemcitabine & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #8, 6/1250 ("GCb6") {{#subobject:afcfd9|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
| rowspan="2" |[https://www.ejcancer.com/article/S0959-8049(17)31001-8 Ferry et al. 2017 (BTOG2)]
 +
| rowspan="2" |2005-2009
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]; GC50
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|
 +
|-
 +
|2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]; GC80
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #9, 300/1000 {{#subobject:9c94c9|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(01)00493-7 Grigorescu et al. 2002]
 +
|1997-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] 300 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Grigorescu AC, Draghici IN, Nitipir C, Gutulescu N, Corlan E. Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial. Lung Cancer. 2002 Jul;37(1):9-14. [https://www.lungcancerjournal.info/article/S0169-5002(01)00493-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12057861 PubMed]
 +
#Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. [https://doi.org/10.1002/cncr.11535 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12879472 PubMed]
 +
#Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. [https://www.lungcancerjournal.info/article/S0169-5002(03)00233-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12928123 PubMed]
 +
#Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, Hatton M, Johnson PW, Martin WM, Rankin EM, James LE, Gregory WM, Qian W, Lee SM; London Lung Cancer Group. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol. 2005 Jan 1;23(1):142-53. [https://doi.org/10.1200/JCO.2005.03.037 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15625369 PubMed]
 +
#Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR; Swedish Lung Cancer Study Group. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [https://doi.org/10.1200/jco.2005.01.2781 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16293868 PubMed]
 +
#Helbekkmo N, Sundstrøm SH, Aasebø U, Brunsvig PF, von Plessen C, Hjelde HH, Garpestad OK, Bailey A, Bremnes RM; Norwegian Lung Cancer Study Group. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer. 2007 Aug 6;97(3):283-9. Epub 2007 Jun 26. [https://www.nature.com/articles/6603869 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360329/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17595658 PubMed]
 +
#Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. [https://doi.org/10.1093/annonc/mdm430 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17938425 PubMed]
 +
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the International Association for the Study of Lung Cancer 12th World Conference on Lung Cancer, September 2-6, 2007, Seoul, Korea. -->
 +
#Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [https://doi.org/10.1200/jco.2008.20.9114 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19433683 PubMed]
 +
#'''ALPHA A1-99002L:''' Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. [https://doi.org/10.1093/annonc/mdp352 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19833819 PubMed] NCT00054392
 +
#'''MCC-15005:''' Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. Epub 2013 May 20. [https://doi.org/10.1200/JCO.2012.46.9783 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691357/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23690416 PubMed] NCT00499109
 +
#'''FASTACT-2:''' Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. [https://doi.org/10.1016/S1470-2045(13)70254-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23782814 PubMed] NCT00883779
 +
#'''NITRO:''' Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. [https://doi.org/10.1093/annonc/mdv373 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26347110/ PubMed] ACTRN12608000588392
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
#'''BTOG2:''' Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K; British Thoracic Oncology Group. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. [https://www.ejcancer.com/article/S0959-8049(17)31001-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28780466 PubMed] NCT00112710
 +
==Carboplatin & Paclitaxel (CP) {{#subobject:c5fbdf|Regimen=1}}==
 +
CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
 +
<br>PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin
 +
<br>TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 5/200 {{#subobject:5g4ff1|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7146551/ Rizvi et al. 2020 (MYSTIC)]
 +
|rowspan=2|2015-2016
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Durvalumab_monotherapy_99|Durvalumab]]
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|
 +
|-
 +
|[[#Durvalumab_.26_Tremelimumab_77|Durvalumab & Tremelimumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 +
|
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*KEYNOTE-024: Patients with nonsquamous histology could optionally proceed to [[#Pemetrexed_monotherapy_2|pemetrexed switch]] maintenance
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 6/175 {{#subobject:e3545d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdh260 Stathopoulos et al. 2004]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Paclitaxel_.26_Vinorelbine_99|Paclitaxel & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/OS
 +
|-
 +
|[https://doi.org/10.1200/jco.2011.38.4032 Lynch et al. 2012 (CA184-041)]
 +
|2008-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|CP & Ipilimumab]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours on days 2 to 4
+
*[[:Category:Steroids|Corticosteroids]] could be used as premedication for [[Paclitaxel (Taxol)]] infusion.
−
====CNS therapy, prophylaxis (group B)====
+
'''21-day cycle for up to 6 cycles'''
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 2 & 6
+
</div></div><br>
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)
+
<div class="toccolours" style="background-color:#eeeeee">
−
====CNS therapy, treatment (group C)====
+
===Regimen variant #3, 6/200 {{#subobject:5f5ff1|Variant=1}}===
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 2, 4, 6
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 2, 4, 6
+
! style="width: 17%" |Study
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 2, 4, 6 (admixed with MTX & Ara-C)
+
! style="width: 15%" |Years of enrollment
−
'''One course'''
+
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2002.20.5.1335 Socinski et al. 2002]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|CP]]; indefinite
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 +
|-
 +
|[https://doi.org/10.1200/JCO.2002.12.112 Kosmidis et al. 2002]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Gemcitabine_.26_Paclitaxel|Gemcitabine & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdf332 Rosell et al. 2002]
 +
|1996-1997
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/jco.2004.11.022 Johnson et al. 2004]
 +
|NR
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|PacCBev]]
 +
| style="background-color:#fc8d59" |Seems to have inferior TTP
 +
|
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.03.2722 Paccagnella et al. 2006]
 +
|1998-2004
 +
| style="background-color:#1a9851" |Phase 2/3 (C)
 +
|[[#PCG_.28Carboplatin.29|PCG]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.04.044 Leighl et al. 2005 (NCIC-CTG BR.18)]
 +
|2000-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_BMS-275291_77|CP & BMS-275291]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
| style="background-color:#1a9850" |Less toxic
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1093/annonc/mdl377 Ohe et al. 2006 (FACS)]
 +
| rowspan="3" |2000-2002
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|
 +
|-
 +
|2. [[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|
 +
|-
 +
|3. [[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.02.840 Herbst et al. 2005 (TRIBUTE)]
 +
|2001-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Erlotinib|CP & Erlotinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://www.clinical-lung-cancer.com/article/S1525-7304(11)70705-7/pdf Schuette et al. 2006]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|CP]]; weekly
 +
| style="background-color:#ffffbf" |Seems to have non-inferior ORR
 +
| style="background-color:#ffffbf" |Mixed toxicity
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.12.2689 Blumenschein et al. 2008 (SPIRIT II)]
 +
|2002-NR
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bexarotene|CP & Bexarotene]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2010.32.8971 Hirsh et al. 2011 (A8501001)]
 +
|2005-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Agatolimod_77|CP & Agatolimod]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.26.1321 Scagliotti et al. 2010 (ESCAPE)]
 +
|2006-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Sorafenib|CP & Sorafenib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2010.31.0326 Okamoto et al. 2010 (LETS)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_S-1_88|Carboplatin & S-1]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/jco.2011.39.5848 Socinski et al. 2012 (CA031)]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_nab-Paclitaxel|Carboplatin & nab-Paclitaxel]]
 +
| style="background-color:#d73027" |Inferior ORR
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.35.0660 Lara et al. 2011 (ATTRACT-1)]
 +
|2008-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Vadimezan_77|CP & Vadimezan]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067944/ Langer et al. 2014 (A4021016)]
 +
|2008-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Figitumumab_77|CP & Figitumumab]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|
 +
|-
 +
|[https://www.ejcancer.com/article/S0959-8049(13)01028-9 Laurie et al. 2013 (NCIC-CTG BR.29)]
 +
|2008-2011
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Cediranib|CP & Cediranib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
| style="background-color:#1a9850" |Less toxic
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(17)30694-0 Herbst et al. 2017 (SWOG S0819)]
 +
|2009-2014
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Cetuximab|CP & Cetuximab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 +
|
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/23/8/1937.full Ramalingam et al. 2016 (M10-898)]
 +
|2012-2013
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[Stub#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Veliparib|CP & Veliparib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7146551/ Rizvi et al. 2020 (MYSTIC)]
 +
|rowspan=2|2015-2016
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Durvalumab_monotherapy_99|Durvalumab]]
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|
 +
|-
 +
|[[#Durvalumab_.26_Tremelimumab_77|Durvalumab & Tremelimumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 +
|
 +
|-
 +
|}
 +
''Note: Patients in TRIBUTE received a maximum of 6 cycles. Patients in SWOG S0819 were EGFR FISH positive.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''21-day cycle for 3 or more cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Socinski et al. 2002, upon progression: Paclitaxel
 +
*KEYNOTE-024: Patients with nonsquamous histology could optionally proceed, after 4 to 6 cycles, to [[#Pemetrexed_monotherapy_2|pemetrexed switch]] maintenance
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 6/225 {{#subobject:847441|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2001.19.13.3210 Kelly et al. 2001 (SWOG 9509)]
 +
|1996-1998
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1056/NEJMoa011954 Schiller et al. 2002 (ECOG E1594)]
 +
| rowspan="3" |1996-1999
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|3. [[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.07.172 Lilenbaum et al. 2005 (CALGB 9730)]
 +
|1997-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Paclitaxel_monotherapy_88|Paclitaxel]]
 +
| style="background-color:#1a9850" |Superior FFS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2004.07.215 Herbst et al. 2004 (INTACT 2)]
 +
|2000-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Gefitinib_99|CP & Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.01.3771 Williamson et al. 2005 (SWOG S0003)]
 +
|2000-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Tirapazamine_77|CP & Tirapazamine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.13.1912 Belani et al. 2008 (BMS TAX/MEN.12)]
 +
|2000-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|CP]]; weekly paclitaxel
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdp352 Treat et al. 2009 (ALPHA A1-99002L)]
 +
|2000-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br> 2. [[#Gemcitabine_.26_Paclitaxel_99|Gemcitabine & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(08)70261-4 Kubota et al. 2008 (JMTO LC00-03)]
 +
|2001-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Vinorelbine_99|Gemcitabine & Vinorelbine]], then [[#Docetaxel_monotherapy_99|Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 14.1 vs 13.6 mo
 +
|-
 +
|[https://www.jto.org/article/S1556-0864(15)31941-9 Weissman et al. 2011 (SR96669)]
 +
|2004-2005 (T)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#GemOx_99|GemOx]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 4.7 vs 4.4 mo
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.21.9618 Lynch et al. 2010 (BMS099)]
 +
|2005-2006 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Cetuximab|CP & Cetuximab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 4.2 vs 4.4 mo<br>(HR 1.11, 95% CI 0.94-1.31)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''21-day cycle for up to 4 cycles (BMS TAX/MEN.12), 6 cycles (SR96669), 10 cycles (SWOG 9509), or indefinitely (ECOG E1594)'''
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*As soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 10<sup>9</sup>/L:
+
*BMS TAX/MEN.12: [[#Paclitaxel_monotherapy_88|Paclitaxel]] maintenance
−
**Group B: [[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] consolidation
+
</div></div>
−
**Group C: [[#CYVE|CYVE]] consolidation
+
===References===
 +
#'''SWOG 9509:''' Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. [https://doi.org/10.1200/JCO.2001.19.13.3210 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11432888 PubMed]
 +
#'''ECOG E1594:''' Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; [[Study_Groups#ECOG|ECOG]]. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [https://doi.org/10.1056/NEJMoa011954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11784875 PubMed]
 +
#Socinski MA, Schell MJ, Peterman A, Bakri K, Yates S, Gitten R, Unger P, Lee J, Lee JH, Tynan M, Moore M, Kies MS. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002 Mar 1;20(5):1335-43. [https://doi.org/10.1200/JCO.2002.20.5.1335 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11870177 PubMed]
 +
#Kosmidis P, Mylonakis N, Nicolaides C, Kalophonos C, Samantas E, Boukovinas J, Fountzilas G, Skarlos D, Economopoulos T, Tsavdaridis D, Papakostas P, Bacoyiannis C, Dimopoulos M. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2002 Sep 1;20(17):3578-85. [https://doi.org/10.1200/JCO.2002.12.112 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12202657 PubMed]
 +
#Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. [https://doi.org/10.1093/annonc/mdf332 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12377641 PubMed]
 +
#'''INTACT 2:''' Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol. 2004 Mar 1;22(5):785-94. [https://doi.org/10.1200/JCO.2004.07.215 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14990633 PubMed]
 +
#Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [https://doi.org/10.1200/jco.2004.11.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15169807 PubMed]
 +
#Stathopoulos GP, Veslemes M, Georgatou N, Antoniou D, Giamboudakis P, Katis K, Tsavdaridis D, Rigatos SK, Dimitroulis I, Bastani S, Loukides S, Vergos K, Marossis K, Grigoratou T, Kalatzi E, Charalambatou M, Paspalli A, Michalopoulou P, Stoka M, Gerogianni A. Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial. Ann Oncol. 2004 Jul;15(7):1048-55. [https://doi.org/10.1093/annonc/mdh260 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15205198 PubMed]
 +
#'''CALGB 9730:''' Lilenbaum RC, Herndon JE 2nd, List MA, Desch C, Watson DM, Miller AA, Graziano SL, Perry MC, Saville W, Chahinian P, Weeks JC, Holland JC, Green MR. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the Cancer and Leukemia Group B (study 9730). J Clin Oncol. 2005 Jan 1;23(1):190-6. [https://doi.org/10.1200/JCO.2005.07.172 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15625373 PubMed] NCT00003117
 +
#'''NCIC-CTG BR.18:''' Leighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, Santoro A, Betticher DC, Gatzemeier U, Jassem J, Crawford J, Tu D, Bezjak A, Humphrey JS, Voi M, Galbraith S, Hann K, Seymour L, Shepherd FA. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. [https://doi.org/10.1200/JCO.2005.04.044 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15837997 PubMed] NCT00006229
 +
#'''TRIBUTE:''' Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5892-9. Epub 2005 Jul 25. [https://doi.org/10.1200/JCO.2005.02.840 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16043829 PubMed] NCT00047736
 +
#'''SWOG S0003:''' Williamson SK, Crowley JJ, Lara PN Jr, McCoy J, Lau DH, Tucker RW, Mills GM, Gandara DR; [[Study_Groups#SWOG|SWOG]]. Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003. J Clin Oncol. 2005 Dec 20;23(36):9097-104. [https://doi.org/10.1200/JCO.2005.01.3771 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16361616 PubMed] NCT00006484
 +
#Schuette W, Blankenburg T, Guschall W, Dittrich I, Schroeder M, Schweisfurth H, Chemaissani A, Schumann C, Dickgreber N, Appel T, Ukena D. Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Clin Lung Cancer. 2006 Mar;7(5):338-43. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)70705-7/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16640806 PubMed]
 +
#Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. [https://doi.org/10.1200/jco.2005.03.2722 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16446341/ PubMed]
 +
#'''FACS:''' Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. [https://doi.org/10.1093/annonc/mdl377 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17079694 PubMed]
 +
#'''BMS TAX/MEN.12:''' Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, Tester WJ. Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol. 2008 Jan 20;26(3):468-73. [https://doi.org/10.1200/JCO.2007.13.1912 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18202422 PubMed] NCT00035152
 +
#'''SPIRIT II:''' Blumenschein GR Jr, Khuri FR, von Pawel J, Gatzemeier U, Miller WH Jr, Jotte RM, Le Treut J, Sun SL, Zhang JK, Dziewanowska ZE, Negro-Vilar A. Phase III trial comparing carboplatin, paclitaxel, and bexarotene with carboplatin and paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT II. J Clin Oncol. 2008 Apr 10;26(11):1879-85. [https://doi.org/10.1200/JCO.2007.12.2689 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18398153 PubMed] NCT00050960
 +
#'''JMTO LC00-03:''' Kubota K, Kawahara M, Ogawara M, Nishiwaki Y, Komuta K, Minato K, Fujita Y, Teramukai S, Fukushima M, Furuse K; Japan Multi-National Trial Organisation. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008 Dec;9(12):1135-42. Epub 2008 Nov 13. [https://doi.org/10.1016/S1470-2045(08)70261-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19013107 PubMed] NCT00079287
 +
#'''ALPHA A1-99002L:''' Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. [https://doi.org/10.1093/annonc/mdp352 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19833819 PubMed] NCT00054392
 +
#'''BMS099:''' Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. [https://doi.org/10.1200/JCO.2009.21.9618 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20100966 PubMed] NCT00112294
 +
#'''ESCAPE:''' Scagliotti G, Novello S, von Pawel J, Reck M, Rodrigues Pereira J, Thomas M, Abrão Miziara JE, Balint B, De Marinis F, Keller A, Arén O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, Dimatteo S, Hanna N. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010 Apr 10;28(11):1835-42. Epub 2010 Mar 8. [https://doi.org/10.1200/JCO.2009.26.1321 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20212250 PubMed] NCT00300885
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/274 Project Data Sphere]
 +
#'''LETS:''' Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K; West Japan Oncology Group. Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a West Japan Oncology Group study. J Clin Oncol. 2010 Dec 20;28(36):5240-6. Epub 2010 Nov 15. [https://doi.org/10.1200/JCO.2010.31.0326 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21079147 PubMed] UMIN000000503
 +
#'''SR96669:''' Weissman CH, Reynolds CH, Neubauer MA, Pritchard S, Kobina S, Asmar L. A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011 Feb;6(2):358-64. [https://www.jto.org/article/S1556-0864(15)31941-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21206386 PubMed] NCT00087802
 +
<!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. -->
 +
#'''A8501001:''' Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE, Szczesna A, Reiterer P, Saleh M, Arrieta O, Bajetta E, Webb RT, Raats J, Benner RJ, Fowst C, Meech SJ, Readett D, Schiller JH. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2011 Jul 1;29(19):2667-74. Epub 2011 May 31. [https://doi.org/10.1200/JCO.2010.32.8971 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21632509 PubMed] NCT00254891
 +
#'''ATTRACT-1:''' Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, Losonczy G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol. 2011 Aug 1;29(22):2965-71. Epub 2011 Jun 27. [https://doi.org/10.1200/JCO.2011.35.0660 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21709202 PubMed] NCT00662597
 +
<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
 +
#'''CA184-041:''' Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.38.4032 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547592 PubMed] NCT00527735
 +
<!-- Presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, June 4-8, 2010; the 47th Annual Meeting of ASCO, Chicago, IL, June 2-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam Rai, the Netherlands, July 3-7, 2011. -->
 +
#'''CA031:''' Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.39.5848 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547591 PubMed] NCT00540514
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/108 Project Data Sphere]
 +
#'''NCIC-CTG BR.29:''' Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer. 2014 Mar;50(4):706-12. Epub 2013 Dec 17. [https://www.ejcancer.com/article/S0959-8049(13)01028-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24360368 PubMed] NCT00795340
 +
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
 +
#'''A4021016:''' Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2. [https://doi.org/10.1200/jco.2013.54.4932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4067944/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24888810 PubMed] NCT00596830
 +
#'''NITRO:''' Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. [https://doi.org/10.1093/annonc/mdv373 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26347110/ PubMed] ACTRN12608000588392
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
#'''M10-898:''' Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E, Urban L, Orlov S, Barlesi F, Kio E, Keiholz U, Qin Q, Qian J, Nickner C, Dziubinski J, Xiong H, Ansell P, McKee M, Giranda V, Gorbunova V. Randomized, placebo-controlled, phase II study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer. Clin Cancer Res. 2017 Apr 15;23(8):1937-1944. Epub 2016 Oct 10. [http://clincancerres.aacrjournals.org/content/23/8/1937.full link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27803064 PubMed] NCT01560104
 +
#'''SWOG S0819:''' Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. [https://doi.org/10.1016/S1470-2045(17)30694-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29169877 PubMed] NCT00946712
 +
#'''MYSTIC:''' Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):661-674. [https://doi.org/10.1001/jamaoncol.2020.0237 link to original article] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7146551/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32271377 PubMed] NCT02453282
 +
#'''ARC-10:''' NCT04736173
 +
==Carboplatin & nab-Paclitaxel {{#subobject:413b7d|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:bcb4af|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2011.39.5848 Socinski et al. 2012 (CA031)]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#1a9850" |Superior ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 (Calvert formula) IV once on day 1, '''given second'''
 +
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, '''given first'''
 +
'''21-day cycle for 6 cycles'''; treatment could continue at physician's discretion if there was no progressive disease or unacceptable toxicity
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''CA031:''' Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.39.5848 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547591 PubMed] NCT00540514
−
# '''LMBA-02:''' Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. [https://doi.org/10.1016/S0140-6736(15)01317-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27080498 PubMed] NCT00180882
+
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/108 Project Data Sphere]
−
==DA-R-EPOCH {{#subobject:3c495a|Regimen=1}}==
+
==Carboplatin & Paclitaxel (CP) & Bevacizumab {{#subobject:1c2c25|Regimen=1}}==
−
DA-R-EPOCH: '''<u>D</u>'''ose '''<u>A</u>'''djusted '''<u>R</u>'''ituximab, '''<u>E</u>'''toposide, '''<u>P</u>'''rednisone, '''<u>O</u>'''ncovin (Vincristine), '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin)
+
PacCBev: '''<u>Pac</u>'''litaxel, '''<u>C</u>'''arboplatin, '''<u>Bev</u>'''acizumab
 +
<br>B+CP: '''<u>B</u>'''evacizumab, '''<u>C</u>'''arboplatin, '''<u>Pac</u>'''litaxel
 +
<br>BCP: '''<u>B</u>'''evacizumab, '''<u>C</u>'''arboplatin, '''<u>Pac</u>'''litaxel
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:de3391|Variant=1}}===
+
===Regimen {{#subobject:7df5c3|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2004.11.022 Johnson et al. 2004]
 +
|NR
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior TTP
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ Dunleavy et al. 2013 (NCI 93-C-0133)]
+
|[https://doi.org/10.1016/S1470-2045(17)30694-0 Herbst et al. 2017 (SWOG S0819)]
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
|2009-2014
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29.2C_Bevacizumab.2C_Cetuximab_99|Carboplatin, Paclitaxel, Bevacizumab, Cetuximab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*SWOG S0819: EGFR FISH positive
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 30 minutes once on day 1, '''given second, starting 60 minutes after the completion of paclitaxel'''
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 3 hours once on day 1
+
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1, '''given third, starting 60 minutes after the completion of carboplatin'''
 +
**Infusion time per Johnson, et al. 2004 was over 90 minutes for cycle 1; if tolerated, given over 30 to 60 minutes for cycles 2 and later
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div>
 +
===References===
 +
#Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [https://doi.org/10.1200/jco.2004.11.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15169807 PubMed]
 +
#'''SWOG S0819:''' Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. [https://doi.org/10.1016/S1470-2045(17)30694-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29169877 PubMed] NCT00946712
 +
==Carboplatin & Paclitaxel (CP) & Ipilimumab {{#subobject:e8ba81|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f70cfc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2011.38.4032 Lynch et al. 2012 (CA184-041)]
 +
|2008-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior PFS
 +
|-
 +
|}
 +
''Note: this is the "phased" approach to this regimen.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 200 mg/m<sup>2</sup>)
+
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
−
*[[Vincristine (Oncovin)]] 0.4 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 1.6 mg/m<sup>2</sup>)
+
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
−
*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV over 2 hours once on day 5
+
====Immunotherapy====
−
*[[Doxorubicin (Adriamycin)]] 10 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 40 mg/m<sup>2</sup>)
+
*[[Ipilimumab (Yervoy)]] as follows:
−
====Glucocorticoid therapy====
+
**Cycles 3 to 6: 10 mg/kg IV once on day 1
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> PO twice per day on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Filgrastim (Neupogen)]] 300 mcg SC once per day, starting on day 6 and continuing until ANC greater than 5000/uL above the nadir level
+
*[[:Category:Steroids|Corticosteroids]] could be used as premedication for [[Paclitaxel (Taxol)]] infusion or for toxicity management.
−
*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] one tablet PO TIW
+
'''21-day cycle for up to 6 cycles'''
−
*[[Omeprazole (Prilosec)]] 20 mg PO once per day or equivalent
+
</div>
−
*[[Docusate (Colace)]] as needed for constipation
+
<div class="toccolours" style="background-color:#cbd5e7">
−
*[[Sennosides (Senna)]] as needed for constipation
+
====Subsequent treatment====
−
*[[Lactulose]] as needed for constipation
+
*Maintenance [[#Ipilimumab_monotherapy|ipilimumab]]
−
====CNS therapy, prophylaxis====
+
</div></div>
−
*[[Methotrexate (MTX)]] as follows:
+
===References===
−
**Cycles 3 to 6: 12 mg IT once per day on days 1 & 5
+
<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
−
'''21-day cycle for 6 cycles if ANC greater than 1000/uL and platelets greater than 100 × 10<sup>9</sup>/L'''
+
#'''CA184-041:''' Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.38.4032 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547592 PubMed] NCT00527735
−
''If counts are below those levels, check daily CBC and continue growth factor support until counts are adequate and next cycle can start.''
+
==Carboplatin & Pemetrexed {{#subobject:920f46|Regimen=1}}==
−
====Dose modifications====
+
CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''emetrexed
−
''Note this is different than some other DA-EPOCH regimens!''
+
<br>Carbo-Pem: '''<u>Carbo</u>'''platin & '''<u>Pem</u>'''etrexed
−
*Start cycle 1 as described above.
+
===Example orders===
−
*Obtain CBCs twice per week for nadir measurements.
+
*[[Example orders for Carboplatin (Paraplatin) and Pemetrexed (Alimta) in non-small cell lung cancer]]
−
*If nadir ANC greater than or equal to 500/uL, increase etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
+
<div class="toccolours" style="background-color:#eeeeee">
−
*If nadir ANC less than 500/uL, use same doses as last cycle.
+
===Regimen variant #1, 5/500 x 6 {{#subobject:f0cdea|Variant=1}}===
−
*If nadir platelet count less than 25 × 10<sup>9</sup>/L, decrease etoposide, doxorubicin, and cyclophosphamide by 20% compared to previous cycle.
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
**''Decreases below the cycle 1 starting dose only apply to cyclophosphamide, i.e., the lowest etoposide and doxorubicin would be dosed is at the original cycle 1 dose.''
+
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
 +
====Supportive therapy====
 +
*(Ardizzoni et al. 2012 contained more details):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycle for up to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Optional [[#Pemetrexed_monotherapy_2|pemetrexed]] maintenance
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 6/500 x 4 {{#subobject:ecc998|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2008.20.9114 Grønberg et al. 2009]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
 +
====Supportive therapy====
 +
*(Ardizzoni et al. 2012 contained more details):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 6/500 x 6 {{#subobject:8aad39|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
 +
====Supportive therapy====
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose prior to [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 1 mg PO once per day
 +
'''21-day cycle for up to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*Optional [[#Pemetrexed_monotherapy_2|pemetrexed]] maintenance
 +
</div></div>
 +
===References===
 +
<!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the International Association for the Study of Lung Cancer 12th World Conference on Lung Cancer, September 2-6, 2007, Seoul, Korea. -->
 +
#Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [https://doi.org/10.1200/jco.2008.20.9114 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19433683 PubMed]
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
==Carboplatin & Vinorelbine {{#subobject:e7a434|Regimen=1}}==
 +
VC: '''<u>V</u>'''inorelbine & '''<u>C</u>'''arboplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, IV vinorelbine {{#subobject:a9c41c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[http://www.lungcancerjournal.info/article/S0169-5002(05)00119-4 Tan et al. 2005 (GLOB 2)]
 +
|2000-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, PO vinorelbine {{#subobject:bd4ba1|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405221/ Fløtten et al. 2012]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 60 mg/m<sup>2</sup> PO once per day on days 1 & 8
 +
'''21-day cycle for 3 cycles'''
 +
</div></div>
 +
===References===
 +
#'''GLOB 2:''' Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. [http://www.lungcancerjournal.info/article/S0169-5002(05)00119-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16022917 PubMed]
 +
#Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. [https://www.nature.com/articles/bjc2012284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405221/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22759880 PubMed] NCT00737867
 +
==Cemiplimab monotherapy {{#subobject:179ig6|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:igjaze|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(21)00228-2 Sezer et al. 2021 (EMPOWER-Lung 1)]
 +
|2017-2020
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br> 2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]<br> 3. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 4. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]<br> 5. [[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]<br> 6. [[#Cisplatin_.26_Pemetrexed_88|Cisplatin & Pemetrexed]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: NYR vs 14.2 mo<br>(HR 0.57, 95% CI 0.42-0.77)
 +
|-
 +
|}
 +
''Note: some of the comparator platinum doublets appear to be histology-specific, but this is not specified in the manuscript or protocol. We have reached out to the authors for clarification. Per Sanofi, "it was strongly recommended that patients with squamous NSCLC do not receive pemetrexed-containing regimens"; otherwise, no histology-specific guidance was provided to the investigator.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*PD-L1 expressed in at least 50% of tumor cells
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Cemiplimab (Libtayo)]] 350 mg IV over 30 minutes once on day 1
 +
'''21-day cycle for up to 36 cycles (2 years)'''
 +
</div></div>
 +
===References===
 +
#'''EMPOWER-Lung 1:''' Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. [https://doi.org/10.1016/s0140-6736(21)00228-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33581821/ PubMed] NCT03088540
 +
==Cisplatin & Docetaxel (DC) {{#subobject:179d86|Regimen=1}}==
 +
DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''isplatin
 +
<br>DP: '''<u>D</u>'''ocetaxel & '''<u>P</u>'''latinol (Cisplatin)
 +
<br>Doc-Cis: '''<u>Doc</u>'''etaxel & '''<u>Cis</u>'''platin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 50/75 {{#subobject:c60a4e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[http://ar.iiarjournals.org/content/33/12/5477.long Berghmans et al. 2013 (ELCWP-01041)]
 +
|2003-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[Non-small_cell_lung_cancer_-_historical#GIP|GIP]]<br> 2. [[Non-small_cell_lung_cancer_-_historical#Ifosfamide_.26_Gemcitabine|IG]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75/75 {{#subobject:154c29|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1056/NEJMoa011954 Schiller et al. 2002 (ECOG E1594)]
 +
| rowspan="3" |1996-1999
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|3. [[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2003.12.046 Fossella et al. 2003 (TAX 326)]
 +
| rowspan="2" |1998-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Docetaxel]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2006.09.7915 Cobo et al. 2007]
 +
|2001-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|ERCC1 mRNA-guided therapy
 +
| style="background-color:#fc8d59" |Seems to have inferior ORR
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdn774 Tan et al. 2009 (GLOB3)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTF
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for up to 6 cycles (GLOB3) or indefinitely (E1594, TAX326)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 80/60 {{#subobject:5a7d3b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2004.06.114 Kubota et al. 2004]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.23.3445 Takeda et al. 2009 (WJTOG0203)]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Regimen_classes#Platinum_doublet|Platinum doublet]] x 3, then [[#Gefitinib_monotherapy_99|Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478975/ Kubota et al. 2015 (TCOG0701 CATS)]
 +
|2007-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_S-1_88|Cisplatin & S-1]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given second'''
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
 +
'''21-day cycle for 3 to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 80/100 {{#subobject:b1a602|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(00)04644-4 Georgoulias et al. 2001]
 +
|1997-1999
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/TTP
 +
|-
 +
|[https://doi.org/10.3816/clc.2003.n.008 Georgoulias et al. 2003]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy_99|Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 2
 +
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, Palamidas P, Vlachonikolis I; Greek Oncology Cooperative Group (GOCG) for Lung Cancer. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet. 2001 May 12;357(9267):1478-84. [https://doi.org/10.1016/S0140-6736(00)04644-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11377599 PubMed]
 +
#'''ECOG E1594:''' Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; [[Study_Groups#ECOG|ECOG]]. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [https://doi.org/10.1056/NEJMoa011954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11784875 PubMed]
 +
#Georgoulias V, Pallis AG, Kourousis C, Alexopoulos A, Ardavanis A, Agelidou A, Agelidou M, Toumbis M, Tzannes S, Pavlakou G, Ziotopoulos P, Tzelepatiotis E, Samaras N; Hellenic Oncology Research Group. Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study. Clin Lung Cancer. 2003 Mar;4(5):288-93. [https://doi.org/10.3816/clc.2003.n.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14609446 PubMed]
 +
##'''Update:''' Georgoulias V, Ardavanis A, Agelidou A, Agelidou M, Chandrinos V, Tsaroucha E, Toumbis M, Kouroussis C, Syrigos K, Polyzos A, Samaras N, Papakotoulas P, Christofilakis C, Ziras N, Alegakis A. Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol. 2004 Jul 1;22(13):2602-9. [https://doi.org/10.1200/JCO.2004.11.004 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15226327 PubMed]
 +
<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
 +
#'''TAX 326:''' Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [https://doi.org/10.1200/jco.2003.12.046 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12837811 PubMed]
 +
#Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. [https://doi.org/10.1200/JCO.2004.06.114 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14722033 PubMed]
 +
#Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, Viñolas N, Paz-Ares L, Lopez-Vivanco G, Muñoz MA, Felip E, Alberola V, Camps C, Domine M, Sanchez JJ, Sanchez-Ronco M, Danenberg K, Taron M, Gandara D, Rosell R. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007 Jul 1;25(19):2747-54. [https://doi.org/10.1200/JCO.2006.09.7915 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17602080 PubMed]
 +
#Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. [https://doi.org/10.1200/JCO.2007.10.8134 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024869 PubMed]
 +
#'''GLOB3:''' Tan EH, Rolski J, Grodzki T, Schneider CP, Gatzemeier U, Zatloukal P, Aitini E, Carteni G, Riska H, Tsai YH, Abratt R. Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and iv vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2009 Jul;20(7):1249-56. Epub 2009 Mar 10. [https://doi.org/10.1093/annonc/mdn774 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19276396 PubMed]
 +
#'''WJTOG0203:''' Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.23.3445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038730 PubMed] NCT00144066
 +
#'''ELCWP-01041:''' Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. [http://ar.iiarjournals.org/content/33/12/5477.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24324084 PubMed] NCT00622349
 +
#'''TCOG0701 CATS:''' Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S; Tokyo Cooperative Oncology Group. A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol. 2015 Jul;26(7):1401-8. Epub 2015 Apr 23. [https://doi.org/10.1093/annonc/mdv190 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478975/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25908605 PubMed] UMIN000000608
 +
==Cisplatin & Etoposide (EP) {{#subobject:0d191d|Regimen=1}}==
 +
PE: '''<u>P</u>'''latinol (Cisplatin) & '''<u>E</u>'''toposide
 +
<br>EC: '''<u>E</u>'''toposide & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 60/360 {{#subobject:2888e6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1986.4.1.14 Ruckdeschel et al. 1986 (ECOG E1581)]
 +
|1981-1983
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[Non-small_cell_lung_cancer_-_historical#CAMP|CAMP]]<br> 2. [[Non-small_cell_lung_cancer_-_historical#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br> 3. [[Non-small_cell_lung_cancer_-_historical#MVP_.28Vinblastine.29|MVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint
 +
|-
 +
|}
 +
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 +
*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 4, 6, 8
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75/300 {{#subobject:5151cf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.3.623 Bonomi et al. 2000 (ECOG E5592)]
 +
|1993-1994
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdi216 Belani et al. 2005]
 +
|1995-1996
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 45 minutes once per day on days 1 to 3
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 100/300 {{#subobject:5281cf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.1.12 Cardenal et al. 1999]
 +
|1995-1996
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#d73027" |Inferior TTP
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 105/600 {{#subobject:5a56cf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/full/10.1002/%28SICI)1097-0142%2819990215%2985%3A4%3C855%3A%3AAID-CNCR12%3E3.0.CO%3B2-R Font et al. 1999]
 +
|1993-1995
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Etoposide_.28EP.29_3|PE]]; dose-dense
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 35 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 120/300 {{#subobject:d94e47|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1990.8.9.1556 Klastersky et al. 1990 (EORTC 07861)]
 +
|1987-1989
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Etoposide_.28CE.29|Carboplatin & Etoposide]]
 +
| style="background-color:#d9ef8b" |Might have superior ORR
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077209/ Comella et al. 1996]
 +
|1993-1995
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin.2C_Cisplatin.2C_Etoposide.2C_Vinorelbine_99|Carboplatin, Cisplatin, Etoposide, Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 120 mg/m<sup>2</sup> IV once on day 1
 +
**Comella et al. 1996 gave 40 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 +
'''3- to 4-week cycles'''
 +
</div></div>
 +
===References===
 +
#'''ECOG E1581:''' Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. [https://doi.org/10.1200/JCO.1986.4.1.14 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/3510278 PubMed]
 +
#'''EORTC 07861:''' Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. [https://doi.org/10.1200/JCO.1990.8.9.1556 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2167953 PubMed]
 +
#Comella P, Frasci G, De Cataldis G, Panza N, Cioffi R, Curcio C, Belli M, Bianco A, Ianniello G, Maiorino L, Della Vittoria M, Perchard J, Comella G; Gruppo Oncologico Campano. Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Br J Cancer. 1996 Dec;74(11):1805-11. [https://doi.org/10.1038/bjc.1996.634 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2077209/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8956797 PubMed]
 +
#Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. [https://doi.org/10.1200/JCO.1999.17.1.12 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458212 PubMed]
 +
#Font A, Moyano AJ, Puerto JM, Tres A, Garcia-Giron C, Barneto I, Anton A, Sanchez JJ, Salvador A, Rosell R; Spanish Lung Cancer Group. Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group. Cancer. 1999 Feb 15;85(4):855-63. [https://doi.org/full/10.1002/%28SICI)1097-0142%2819990215%2985%3A4%3C855%3A%3AAID-CNCR12%3E3.0.CO%3B2-R link to original article] [https://pubmed.ncbi.nlm.nih.gov/10091762 PubMed]
 +
#'''ECOG E5592:''' Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. [https://doi.org/10.1200/JCO.2000.18.3.623 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10653877 PubMed]
 +
#Belani CP, Lee JS, Socinski MA, Robert F, Waterhouse D, Rowland K, Ansari R, Lilenbaum R, Natale RB. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol. 2005 Jul;16(7):1069-75. Epub 2005 Apr 28. [https://doi.org/10.1093/annonc/mdi216 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15860487 PubMed]
 +
==Cisplatin & Gemcitabine (GC) {{#subobject:fb3ee0|Regimen=1}}==
 +
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin
 +
<br>GP: '''<u>G</u>'''emcitabine & '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 70/1000 {{#subobject:b0126d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.10.8134 Park et al. 2007]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]; 6 cycles
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75/1250 q3wk {{#subobject:0e126e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.03.170 Bissett et al. 2005 (AG-3340-017)]
 +
|1999-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Prinomastat_77|GC & Prinomastat]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdm061 Novello et al. 2007]
 +
|2001-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] x 2, then gemcitabine x 3
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdr030 Manegold et al. 2011]
 +
|2005-2007
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|GC & PF-3512676
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_monotherapy_2|Pembrolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
| style="background-color:#d73027" |Inferior HRQoL
 +
|-
 +
|}
 +
''Note: Patients in Novello et al. 2007 received 5 cycles. Patients in KEYNOTE-024 received 4 to 6 cycles.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles (see note)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 75/1250 q4wk {{#subobject:64837d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70254-7 Wu et al. 2013 (FASTACT-2)]
 +
|2009-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer,_EGFR-mutated#Cisplatin_.26_Gemcitabine.2FErlotinib|GC/Erlotinib]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
''Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''28-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 80/1000 {{#subobject:816a83|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1093/annonc/mdl377 Ohe et al. 2006 (FACS)]
 +
| rowspan="3" |2000-2002
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|2. [[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|3. [[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.23.3445 Takeda et al. 2009 (WJTOG0203)]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Regimen_classes#Platinum_doublet|Platinum doublet]] x 3, then [[#Gefitinib_monotherapy_99|Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 6 cycles (WJTOG0203) or indefinitely (FACS)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 80/1125 {{#subobject:10bc56|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394313/ Wachters et al. 2003]
 +
|1998-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Epirubicin_.26_Gemcitabine_99|Epirubicin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 2
 +
*[[Gemcitabine (Gemzar)]] 1125 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 5 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #6, 80/1200 x 6 {{#subobject:744a8d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2003.06.099 Gridelli et al. 2003 (NCIC-CTG BR.14)]
 +
|1998-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(07)70146-8 Gridelli et al. 2007 (GECO)]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Rofecoxib_99|GC & Rofecoxib]]<br> 2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]; PCI gemcitabine<br> 3. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Rofecoxib_99|GC & Rofecoxib]]; PCI gemcitabine
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.41.2056 Gridelli et al. 2012 (TORCH)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Erlotinib_monotherapy_99|Erlotinib]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 11.6 vs 8.7 mo<br>(HR 0.81, 95% CI 0.68-0.96)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*TORCH, at progression: [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #7, 80/1250 x 4 {{#subobject:f2149d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://www.ejcancer.com/article/S0959-8049(17)31001-8 Ferry et al. 2017 (BTOG2)]
 +
|rowspan=2|2005-2009
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]]; GC50
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|2. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb6]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2011.39.9782 Pérol et al. 2012 (IFCT-GFPC 0502)]
 +
|2006-2009
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 4 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*IFCT-GFPC 0502: [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy|Erlotinib switch]] versus [[#Gemcitabine_monotherapy_2|gemcitabine]] maintenance versus [[Non-small_cell_lung_cancer_-_null_regimens#Observation_3|observation]]
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #8, 80/1250 x 6 {{#subobject:646326|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2004.08.001 Giaccone et al. 2004 (INTACT 1)]
 +
|2000-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Gefitinib_99|GC & Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.05.1474 Gatzemeier et al. 2007 (TALENT)]
 +
|2001-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Erlotinib_99|GC & Erlotinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322957/ Boni et al. 2012 (FAST)]
 +
|rowspan=2|2001-2006
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#GIN_99|GIN]]<br>2. [[#Gemcitabine_.26_Vinorelbine_.28GN.29_99|GN]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|3. [[Non-small_cell_lung_cancer_-_historical#GIP|GIP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.04.3299 Paz-Ares et al. 2006]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Aprinocarsen_77|GC & Aprinocarsen]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #9, 100/1000 q3wk {{#subobject:ec88d3|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.spandidos-publications.com/ijo/39/4/1011 Ridolfi et al. 2011]
 +
|2000-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Cisplatin_.28GC.29_.26_LD_IL-2_99|GC & LD IL-2]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #10, 100/1000 q4wk {{#subobject:a352e8|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.11.3522 Crinò et al. 1999]
 +
|1995-1997
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer_-_historical#MIC_2|MIC]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.1.122 Sandler et al. 2000]
 +
|1995-1997
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_monotherapy|Cisplatin]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1056/NEJMoa011954 Schiller et al. 2002 (ECOG E1594)]
 +
| rowspan="3" |1996-1999
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|3. [[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.2007.15.0375 Scagliotti et al. 2008 (JMDB)]
 +
|2004-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #11, 100/1250 {{#subobject:8bb0be|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.1.12 Cardenal et al. 1999]
 +
|1995-1996
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|[[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]]
 +
| style="background-color:#1a9850" |Superior TTP
 +
|-
 +
|[https://doi.org/10.1200/JCO.2003.12.038 Alberola et al. 2003]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[Stub#PGV|CGV]]<br> 2. [[#GV-VI_99|GV-VI]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 6 cycles (Alberola et al. 2003) or indefinitely (Cardenal et al. 1999)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #12, 100/1400 {{#subobject:b9409e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(02)00444-0 Gebbia et al. 2003]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1400 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. [https://doi.org/10.1200/JCO.1999.17.1.12 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10458212 PubMed]
 +
#Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. [https://doi.org/10.1200/JCO.1999.17.11.3522 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10550150 PubMed]
 +
#Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122-30. [https://doi.org/10.1200/JCO.2000.18.1.122 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10623702 PubMed]
 +
#'''ECOG E1594:''' Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; [[Study_Groups#ECOG|ECOG]]. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [https://doi.org/10.1056/NEJMoa011954 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11784875 PubMed]
 +
#Gebbia V, Galetta D, Caruso M, Verderame F, Pezzella G, Valdesi M, Borsellino N, Pandolfo G, Durini E, Rinaldi M, Loizzi M, Gebbia N, Valenza R, Tirrito ML, Varvara F, Colucci G; Gruppo Ocologico Italia Meridionale. Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale. Lung Cancer. 2003 Feb;39(2):179-89. [https://www.lungcancerjournal.info/article/S0169-5002(02)00444-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12581571 PubMed]
 +
#'''NCIC-CTG BR.14:''' Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. [https://doi.org/10.1200/JCO.2003.06.099 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12837810 PubMed] NCT00004100
 +
#Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, Ruiz-Casado A, Azagra P, Jiménez U, González-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Peñas R, Felip E, López-Vivanco G; Spanish Lung Cancer Group. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol. 2003 Sep 1;21(17):3207-13. [https://doi.org/10.1200/JCO.2003.12.038 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12947054 PubMed]
 +
#Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. [https://www.lungcancerjournal.info/article/S0169-5002(03)00233-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12928123 PubMed]
 +
#Wachters FM, Van Putten JW, Kramer H, Erjavec Z, Eppinga P, Strijbos JH, de Leede GP, Boezen HM, de Vries EG, Groen HJ. First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial. Br J Cancer. 2003 Oct 6;89(7):1192-9. [https://www.nature.com/articles/6601283 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394313/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14520444 PubMed]
 +
#'''INTACT 1:''' Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol. 2004 Mar 1;22(5):777-84. [https://doi.org/10.1200/JCO.2004.08.001 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14990632 PubMed]
 +
#'''AG-3340-017:''' Bissett D, O'Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, Mercier R, Mazabel E, Penning C, Zhang MH, Collier MA, Shepherd FA. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol. 2005 Feb 1;23(4):842-9. [https://doi.org/10.1200/JCO.2005.03.170 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15681529 PubMed] NCT00004199
 +
#Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, Chang GC, John WJ, Peterson PM, Obasaju CK, Lahn M, Gandara DR. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2006 Mar 20;24(9):1428-34. [https://doi.org/10.1200/JCO.2005.04.3299 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16549837 PubMed]
 +
#'''FACS:''' Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. [https://doi.org/10.1093/annonc/mdl377 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17079694 PubMed]
 +
#Novello S, Bruzzi P, Barone C, Buosi R, Masotti A, Michetti G, Fioretti M, Barbera S, Spatafora M, Garetto L, Mazzanti P, Dongiovanni V, Selvaggi G, Crinò L, Scagliotti GV. Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone. Ann Oncol. 2007 May;18(5):903-8. Epub 2007 Mar 9. [https://doi.org/10.1093/annonc/mdm061 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17351253 PubMed]
 +
#'''TALENT:''' Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007 Apr 20;25(12):1545-52. [https://doi.org/10.1200/JCO.2005.05.1474 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17442998 PubMed]
 +
#'''GECO:''' Gridelli C, Gallo C, Ceribelli A, Gebbia V, Gamucci T, Ciardiello F, Carozza F, Favaretto A, Daniele B, Galetta D, Barbera S, Rosetti F, Rossi A, Maione P, Cognetti F, Testa A, Di Maio M, Morabito A, Perrone F; GECO investigators. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol. 2007 Jun;8(6):500-12. [https://doi.org/10.1016/S1470-2045(07)70146-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17513173 PubMed] NCT00385606
 +
#Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. [https://doi.org/10.1200/JCO.2007.10.8134 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024869 PubMed]
 +
#'''JMDB:''' Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [https://doi.org/10.1200/jco.2007.15.0375 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18506025 PubMed] NCT00087711
 +
#'''WJTOG0203:''' Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.23.3445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038730 PubMed] NCT00144066
 +
#Manegold C, van Zandwijk N, Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M, Serwatowski P, Krzakowski M, Jassem J, Tan EH, Benner RJ, Ingrosso A, Meech SJ, Readett D, Thatcher N. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2012 Jan;23(1):72-7. Epub 2011 Apr 4. [https://doi.org/10.1093/annonc/mdr030 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21464154 PubMed]
 +
#Ridolfi L, Bertetto O, Santo A, Naglieri E, Lopez M, Recchia F, Lissoni P, Galliano M, Testore F, Porta C, Maglie M, Dall'agata M, Fumagalli L, Ridolfi R. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial. Int J Oncol. 2011 Oct;39(4):1011-7. Epub 2011 Jun 24. [https://www.spandidos-publications.com/ijo/39/4/1011 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21720704 PubMed]
 +
#'''FAST:''' Boni C, Tiseo M, Boni L, Baldini E, Recchia F, Barone C, Grossi F, Germano D, Matano E, Marini G, Labianca R, Di Costanzo F, Bagnulo A, Pennucci C, Caroti C, Mencoboni M, Zanelli F, Prochilo T, Cafferata MA, Ardizzoni A; Gruppo Oncologico Italiano di Ricerca Clinica. Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST). Br J Cancer. 2012 Feb 14;106(4):658-65. Epub 2012 Jan 12. [https://www.nature.com/articles/bjc2011606 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3322957/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22240782 PubMed]
 +
#'''TORCH:''' Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012 Aug 20;30(24):3002-11. Epub 2012 Jul 9. [https://doi.org/10.1200/JCO.2011.41.2056 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22778317 PubMed] NCT00349219
 +
##'''HRQoL analysis:''' Di Maio M, Leighl NB, Gallo C, Feld R, Ciardiello F, Butts C, Maione P, Gebbia V, Morgillo F, Wierzbicki R, Favaretto A, Alam Y, Cinieri S, Siena S, Bianco R, Riccardi F, Spatafora M, Ravaioli A, Felletti R, Fregoni V, Genestreti G, Rossi A, Mancuso G, Fasano M, Morabito A, Tsao MS, Signoriello S, Perrone F, Gridelli C. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advancednon-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1830-1844. [https://www.jto.org/article/S1556-0864(15)33167-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23154555 PubMed]
 +
#'''IFCT-GFPC 0502:''' Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. [https://doi.org/10.1200/JCO.2011.39.9782 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22949150 PubMed] NCT00300586
 +
#'''FASTACT-2:''' Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. [https://doi.org/10.1016/S1470-2045(13)70254-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23782814 PubMed] NCT00883779
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
#'''BTOG2:''' Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. [https://www.ejcancer.com/article/S0959-8049(17)31001-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28780466 PubMed] NCT00112710
 +
==Cisplatin & Gemcitabine (GC) & Cetuximab {{#subobject:fb3990|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:b02hcd|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"
 +
! style="width: 33%" |Study
 +
! style="width: 33%" |Years of enrollment
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2007.13.0856 Butts et al. 2008]
 +
|NR
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|-
 +
|}
 +
''Note: this was a non-comparative study.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
====Targeted therapy====
 +
*[[Cetuximab (Erbitux)]] as follows:
 +
**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once per day on days 8 & 15
 +
**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div>
 +
===References===
 +
#Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, Kreisman H, Graze P, Maher J, Ross HJ, Ellis PM, McNulty W, Kaplan E, Pautret V, Weber MR, Shepherd FA. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol. 2007 Dec 20;25(36):5777-84. Erratum in: J Clin Oncol. 2008 Jul 1;26(19): 3295. [https://doi.org/10.1200/jco.2007.13.0856 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089875 PubMed]
 +
==Cisplatin & Irinotecan (IC) {{#subobject:c1250d|Regimen=1}}==
 +
IP: '''<u>I</u>'''rinotecan & '''<u>P</u>'''latinol (Cisplatin)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4cf321|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ Negoro et al. 2003]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[[#Irinotecan_monotherapy_88|Irinotecan]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1093/annonc/mdl377 Ohe et al. 2006 (FACS)]
 +
| rowspan="3" |2000-2002
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|3. [[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.23.3445 Takeda et al. 2009 (WJTOG0203)]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Regimen_classes#Platinum_doublet|Platinum doublet]] x 3, then [[#Gefitinib_monotherapy_99|Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycle for up to 6 cycles (WJTOG0203) or indefinitely (FACS)'''
 +
</div></div>
 +
===References===
 +
#Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. [https://www.nature.com/articles/6600725 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747545/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12569373 PubMed]
 +
#'''FACS:''' Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. [https://doi.org/10.1093/annonc/mdl377 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17079694 PubMed]
 +
#'''WJTOG0203:''' Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.23.3445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038730 PubMed] NCT00144066
 +
==Cisplatin & Paclitaxel {{#subobject:7f19fc|Regimen=1}}==
 +
PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 70/175 x 4 {{#subobject:a142cf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.10.8134 Park et al. 2007]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] x 6
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 70/175 x 6 {{#subobject:a16yqf|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.10.8134 Park et al. 2007]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]] x 4
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|[https://doi.org/10.1016/j.annonc.2020.10.479 Shi et al. 2020 (PM-03-2015)]
 +
|2015-2018
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Paclitaxel_micellar_77|Cisplatin & Paclitaxel micellar]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 75/135, q2wk {{#subobject:df98d7|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962260/ Stathopoulos et al. 2010a]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_liposomal_.26_Paclitaxel_77|Liposomal Cisplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet secondary endpoints
 +
| style="background-color:#d73027" |More toxic
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''14-day cycle for up to 9 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 75/135, q3wk {{#subobject:5f385|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.3.623 Bonomi et al. 2000 (ECOG E5592)]
 +
|1993-1994
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|[[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1056/NEJMoa011954 Schiller et al. 2002 (ECOG E1594)]
 +
| rowspan="3" |1996-1999
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|3. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 2, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, '''given first'''
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 80/175 {{#subobject:2730a0|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.19.3390 Gatzemeier et al. 2000]
 +
|1995-1996
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_monotherapy|Cisplatin]]
 +
| style="background-color:#91cf60" |Seems to have superior TTP
 +
|-
 +
|[https://doi.org/10.1200/JCO.2003.03.195 Smit et al. 2003 (EORTC 08975)]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]<br> 2. [[#Gemcitabine_.26_Paclitaxel_99|Gemcitabine & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #6, 80/200 {{#subobject:96cd6e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdf332 Rosell et al. 2002]
 +
|1996-1997
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''ECOG E5592:''' Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. [https://doi.org/10.1200/JCO.2000.18.3.623 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10653877 PubMed]
 +
#Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. [https://doi.org/10.1200/JCO.2000.18.19.3390 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11013280 PubMed]
 +
#'''ECOG E1594:''' Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; [[Study_Groups#ECOG|ECOG]]. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [https://doi.org/10.1056/NEJMoa011954 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11784875 PubMed]
 +
#Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. [https://doi.org/10.1093/annonc/mdf332 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12377641 PubMed]
 +
#'''EORTC 08975:''' Smit EF, van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, Smit H, Gaafar R, Biesma B, Manegold C, Neymark N, Giaccone G; [[Study_Groups#EORTC|EORTC]] Lung Cancer Group. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organisation for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol. 2003 Nov 1;21(21):3909-17. [https://doi.org/10.1200/JCO.2003.03.195 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14581415 PubMed] NCT00003589
 +
#Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. [https://doi.org/10.1200/JCO.2007.10.8134 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18024869 PubMed]
 +
#Stathopoulos GP, Antoniou D, Dimitroulis J, Michalopoulou P, Bastas A, Marosis K, Stathopoulos J, Provata A, Yiamboudakis P, Veldekis D, Lolis N, Georgatou N, Toubis M, Pappas Ch, Tsoukalas G. Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial. Ann Oncol. 2010 Nov;21(11):2227-32. Epub 2010 May 3. [https://doi.org/10.1093/annonc/mdq234 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2962260/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20439345 PubMed]
 +
#'''PM-03-2015:''' Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, Wang X, Cao L, Shu Y, Wang H, Yang R, Li X, Chang J, Hu Y, Shen P, Hu Y, Guo Z, Tao M, Zhang Y, Liu X, Sun Q, Zhang X, Jiang Z, Zhao J, Chen F, Yu H, Zhang W, Sun J, Li D, Zhou J, Han B, Wu YL. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021 Jan;32(1):85-96. Epub 2020 Oct 29. [https://doi.org/10.1016/j.annonc.2020.10.479 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33130217 PubMed] NCT02667743
 +
==Cisplatin & Vinorelbine (CVb) {{#subobject:bdd6b2|Regimen=1}}==
 +
CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine
 +
<br>CV: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorelbine
 +
<br>NP: '''<u>N</u>'''avelbine (Vinorelbine) & '''<u>P</u>'''latinol (Cisplatin)
 +
<br>PV: '''<u>P</u>'''latinol (Cisplatin) & '''<u>V</u>'''inorelbine
 +
<br>VC: '''<u>V</u>'''inorelbine & '''<u>C</u>'''isplatin
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 75/25 {{#subobject:21f9be|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ejcancer.com/article/S0959-8049(04)00772-5 Martoni et al. 2005]
 +
|1998-2003
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[#Vinorelbine_monotherapy_88|Vinorelbine]] maintenance
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 80/25 {{#subobject:daeaf6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="3" |[https://doi.org/10.1093/annonc/mdl377 Ohe et al. 2006 (FACS)]
 +
| rowspan="3" |2000-2002
 +
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|3. [[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.23.3445 Takeda et al. 2009 (WJTOG0203)]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Regimen_classes#Platinum_doublet|Platinum doublet]] x 3, then [[#Gefitinib_monotherapy_99|Gefitinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(09)60569-9 Pirker et al. 2009 (FLEX)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin.2C_Vinorelbine.2C_Cetuximab|Cisplatin, Vinorelbine, Cetuximab]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles (FLEX; WJTOG0203) or indefinitely (FACS)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 80/30, 2 out of 3 weeks vinorelbine {{#subobject:6c3243|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2003.06.099 Gridelli et al. 2003 (NCIC-CTG BR.14)]
 +
|1998-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.04.016 Georgoulias et al. 2005]
 +
|1999-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(08)00009-3 Gebbia et al. 2008]
 +
|2003-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]; 3 out of 4 weeks
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
| style="background-color:#1a9850" |Less toxic
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 8
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for 6 cycles (Gridelli et al. 2003) or up to 9 cycles (Georgoulias et al. 2005)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 80/30, weekly vinorelbine {{#subobject:6c3243|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/oxfordjournals.annonc.a058687 Depierre et al. 1994]
 +
|1989-1991
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Vinorelbine_monotherapy_88|Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior TTP
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdf316 Souquet et al. 2002 (GLOB-1)]
 +
|1998-1999
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#NIP|NIP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS1
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 100/25 {{#subobject:45998f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1998.16.7.2459 Wozniak et al. 1998]
 +
|1993-1995
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_historical#Cisplatin_monotherapy|Cisplatin]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2001.19.13.3210 Kelly et al. 2001 (SWOG 9509)]
 +
|1996-1998
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2002.02.068 Scagliotti et al. 2002]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]<br> 2. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/jco.2003.12.046 Fossella et al. 2003 (TAX 326)]
 +
| rowspan="2" |1998-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Cisplatin_.26_Docetaxel_.28DC.29_3|Cisplatin & Docetaxel]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.12.2614 Ramlau et al. 2008 (SPIRIT I)]
 +
|2003-NR
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Vinorelbine_.28CVb.29_.26_Bexarotene_99|CVb & Bexarotene]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
'''28-day cycle for up to 10 cycles (SWOG 9509) or indefinitely (TAX 326, SPIRIT I)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #6, 100/30 {{#subobject:cda93a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdi126 Pujol et al. 2005]
 +
|1999-2001
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 to 120 minutes once on day 1
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 10 to 20 minutes once per day on days 1, 8, 15, 22
 +
'''28-day cycle for 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #7, 120/30 {{#subobject:2bf191|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/JCO.1994.12.2.360 Le Chevalier et al. 1994]
 +
| rowspan="2" |1989-1991
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|1. [[#Cisplatin_.26_Vindesine_88|Cisplatin & Vindesine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|2. [[#Vinorelbine_monotherapy_88|Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/JCO.2000.18.7.1451 Comella et al. 2000]
 +
| rowspan="2" |1997-1999
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Stub#PGV|PGV]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
''Note: in Comella et al. 2000, vinorelbine was given for a total of 10 weeks.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 120 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] as follows:
 +
**Cycle 1: 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
**Cycle 2 onwards: 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36
 +
'''28-day cycle for 1 cycle, then 42-day cycles (see note)'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- # Dunleavy K, Little RF, Pittaluga S, Grant N, Shovlin M, Steinberg S, Yarchoan R, Janik J, Jaffe ES, Wilson WH. A prospective study of dose-adjusted (DA) EPOCH with rituximab in adults with newly diagnosed Burkitt lymphoma: a regimen with high efficacy and low toxicity. Ann Oncol 19(suppl4):83-84, abstr.9. 2008 Jun. [http://annonc.oxfordjournals.org/content/19/suppl_4.toc link to original article] '''contains dosing details in abstract''' -->
+
#Depierre A, Chastang C, Quoix E, Lebeau B, Blanchon F, Paillot N, Lemarie E, Milleron B, Moro D, Clavier J, Herman D, Tuchais E, Jacoulet P, Brechot JM, Cordier JF, Solal-Celigny P, Badri N, Besenval M. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37-42. [https://doi.org/10.1093/oxfordjournals.annonc.a058687 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8172790 PubMed]
−
# '''NCI 93-C-0133:''' Dunleavy K, Pittaluga S, Shovlin M, Steinberg SM, Cole D, Grant C, Widemann B, Staudt LM, Jaffe ES, Little RF, Wilson WH. Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013 Nov 14;369(20):1915-25. [https://doi.org/10.1056/NEJMoa1308392 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1308392/suppl_file/nejmoa1308392_appendix.pdf link to supplement] '''contains dosing details in supplement''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3901044/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24224624 PubMed] NCT00001337
+
#Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. [https://doi.org/10.1200/JCO.1994.12.2.360 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8113844 PubMed]
−
==GMALL-R {{#subobject:630893|Regimen=1}}==
+
#Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR, Livingston RB; [[Study_Groups#SWOG|SWOG]]. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459-65. [https://doi.org/10.1200/JCO.1998.16.7.2459 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9667264 PubMed]
−
GMALL-R: '''<u>G</u>'''erman '''<u>M</u>'''ulticenter Study Group for the Treatment of Adult '''<u>A</u>'''cute '''<u>L</u>'''ymphoblastic '''<u>L</u>'''eukemia, '''<u>R</u>'''ituximab
+
#Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G; Southern Italy Cooperative Oncology Group. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol. 2000 Apr;18(7):1451-7. [https://doi.org/10.1200/JCO.2000.18.7.1451 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10735892 PubMed]
 +
#'''SWOG 9509:''' Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. [https://doi.org/10.1200/JCO.2001.19.13.3210 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11432888 PubMed]
 +
#Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. [https://doi.org/10.1200/JCO.2002.02.068 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12409326 PubMed]
 +
#'''GLOB-1:''' Souquet PJ, Tan EH, Rodrigues Pereira J, Van Klaveren R, Price A, Gatzemeier U, Jaworski M, Burillon JP, Aubert D. GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients. Ann Oncol. 2002 Dec;13(12):1853-61. Erratum in: Ann Oncol. 2003 Feb;14(2):347. [https://doi.org/10.1093/annonc/mdf316 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12453852 PubMed]
 +
<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
 +
#'''TAX 326:''' Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [https://doi.org/10.1200/jco.2003.12.046 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12837811 PubMed]
 +
#'''NCIC-CTG BR.14:''' Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. [https://doi.org/10.1200/JCO.2003.06.099 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12837810 PubMed] NCT00004100
 +
#Martoni A, Marino A, Sperandi F, Giaquinta S, Di Fabio F, Melotti B, Guaraldi M, Palomba G, Preti P, Petralia A, Artioli F, Picece V, Farris A, Mantovani L. Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer. Eur J Cancer. 2005 Jan;41(1):81-92. [https://www.ejcancer.com/article/S0959-8049(04)00772-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15617993 PubMed]
 +
#Georgoulias V, Ardavanis A, Tsiafaki X, Agelidou A, Mixalopoulou P, Anagnostopoulou O, Ziotopoulos P, Toubis M, Syrigos K, Samaras N, Polyzos A, Christou A, Kakolyris S, Kouroussis C, Androulakis N, Samonis G, Chatzidaki D. Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2005 May 1;23(13):2937-45. Epub 2005 Feb 22. [https://doi.org/10.1200/JCO.2005.04.016 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15728228 PubMed]
 +
#Pujol JL, Breton JL, Gervais R, Rebattu P, Depierre A, Morère JF, Milleron B, Debieuvre D, Castéra D, Souquet PJ, Moro-Sibilot D, Lemarié E, Kessler R, Janicot H, Braun D, Spaeth D, Quantin X, Clary C. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005 Apr;16(4):602-10. Epub 2005 Mar 1. [https://doi.org/10.1093/annonc/mdi126 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15741225 PubMed]
 +
#'''FACS:''' Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. [https://doi.org/10.1093/annonc/mdl377 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17079694 PubMed]
 +
#Gebbia V, Galetta D, Lorusso V, Caruso M, Verderame F, Pezzella G, Borsellino N, Durini E, Valenza R, Agostara B, Colucci G; Gruppo Oncologico Italia Meridionale. Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the GOIM (Gruppo Oncologico Italia Meridionale). Lung Cancer. 2008 Sep;61(3):369-77. Epub 2008 Mar 4. [https://www.lungcancerjournal.info/article/S0169-5002(08)00009-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18308419 PubMed]
 +
#'''SPIRIT I:''' Ramlau R, Zatloukal P, Jassem J, Schwarzenberger P, Orlov SV, Gottfried M, Rodrigues Pereira J, Temperley G, Negro-Vilar R, Rahal S, Zhang JK, Negro-Vilar A, Dziewanowska ZE. Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. J Clin Oncol. 2008 Apr 10;26(11):1886-92. [https://doi.org/10.1200/JCO.2007.12.2614 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18398154 PubMed] NCT00050973
 +
#'''FLEX:''' Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. [https://doi.org/10.1016/S0140-6736(09)60569-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19410716 PubMed] NCT00148798
 +
#'''WJTOG0203:''' Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. [https://doi.org/10.1200/JCO.2009.23.3445 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20038730 PubMed] NCT00144066
 +
==Cisplatin, Vinorelbine, Cetuximab {{#subobject:9c28e0|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:724602|Variant=1}}===
+
===Regimen {{#subobject:b4c5e3|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(09)60569-9 Pirker et al. 2009 (FLEX)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Cisplatin_.26_Vinorelbine_3|Cisplatin & Vinorelbine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
====Targeted therapy====
 +
*[[Cetuximab (Erbitux)]] as follows:
 +
**Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 & 15
 +
**Cycles 2 to 6: 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 +
'''21-day cycle for up to 6 cycles'''
 +
</div>
 +
<div class="toccolours" style="background-color:#cbd5e7">
 +
====Subsequent treatment====
 +
*[[#Cetuximab_monotherapy_88|Cetuximab]] maintenance
 +
</div></div>
 +
===References===
 +
#'''FLEX:''' Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. [https://doi.org/10.1016/S0140-6736(09)60569-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19410716 PubMed] NCT00148798
 +
==Docetaxel & Vinorelbine {{#subobject:18h94c|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:abi4b2|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 50%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.27918 Ribera et al. 2013 (Burkimab)]
+
|[https://doi.org/10.1200/JCO.2000.18.6.1346 Miller et al. 2000]
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
−
''Note: Numbering of days is based on prephase->A->B->C; however, certain patient populations received different ordering of regimen, see below.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, prephase====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
+
*[[Docetaxel (Taxotere)]]
−
====Glucocorticoid therapy, prephase====
+
*[[Vinorelbine (Navelbine)]]
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
====Targeted therapy, A cycle====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 7
 
−
====Chemotherapy, A cycle====
 
−
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 8
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 8
 
−
*[[Ifosfamide (Ifex)]] 800 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8 to 12
 
−
*[[Teniposide (Vumon)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 11 & 12
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria:
 
−
**55 or younger: 150 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12
 
−
**Older than 55 years: 75 mg/m<sup>2</sup> IV over 60 minutes twice per day on days 11 & 12
 
−
====Glucocorticoid therapy, A cycle====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 8 to 12
 
−
====Supportive therapy, A cycle====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
====Targeted therapy, B cycle====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 28
 
−
====Chemotherapy, B cycle====
 
−
*[[Vincristine (Oncovin)]] 2 mg IV bolus once on day 29
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 29
 
−
*[[Cyclophosphamide (Cytoxan)]] 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 29 to 33
 
−
*[[Doxorubicin (Adriamycin)]] 25 mg/m<sup>2</sup> IV over 15 minutes once per day on days 32 & 33
 
−
====Glucocorticoid therapy, B cycle====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 29 to 33
 
−
====Supportive therapy, B cycle====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
====Targeted therapy, C cycle====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV over 4 hours once on day 49
 
−
====Chemotherapy, C cycle====
 
−
*[[Vindesine (Eldisine)]] 3 mg/m<sup>2</sup> (maximum dose of 5 mg) IV bolus once on day 50
 
−
*[[Methotrexate (MTX)]] by the following age-based criteria, starting on day 50:
 
−
**55 or younger: 1500 mg/m<sup>2</sup> IV continuous infusion over 24 hours
 
−
**Older than 55 years: 750 mg/m<sup>2</sup> IV continuous infusion over 24 hours
 
−
*[[Etoposide (Vepesid)]] 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 53 & 54
 
−
*[[Cytarabine (Ara-C)]] by the following age-based criteria, on day 54:
 
−
**55 or younger: 2000 mg/m<sup>2</sup> IV over 3 hours twice per day
 
−
**Older than 55 years: 1000 mg/m<sup>2</sup> IV over 3 hours twice per day
 
−
====Glucocorticoid therapy, C cycle====
 
−
*[[Dexamethasone (Decadron)]] 10 mg/m<sup>2</sup> IV bolus once per day on days 50 to 54
 
−
====Supportive therapy, C cycle====
 
−
*[[Folinic acid (Leucovorin)]] (dose/route/schedule not specified), starting 12 hours after [[Methotrexate (MTX)]] infusion
 
−
'''Give regimen by the following criteria:'''
 
−
*'''Advanced stage and younger than 55 years: A->B->C for 2 courses (6 total cycles)'''
 
−
*'''Older than 55 years: Alternate A & B for 3 courses (6 total cycles)'''
 
−
*'''Localized stage: 4 total cycles (unclear from protocol if this means A alternating with B or A->B->C->A)'''
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 1, 8, 12, 29, 33
 
−
*[[Cytarabine (Ara-C)]] 40 mg IT once per day on days 1, 8, 12, 29, 33
 
−
*[[Dexamethasone (Decadron)]] 20 mg IT once per day on days 1, 8, 12, 29, 33
 
−
'''8 doses total'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Burkimab:''' Ribera JM, García O, Grande C, Esteve J, Oriol A, Bergua J, González-Campos J, Vall-Llovera F, Tormo M, Hernández-Rivas JM, García D, Brunet S, Alonso N, Barba P, Miralles P, Llorente A, Montesinos P, Moreno MJ, Hernández-Rivas JÁ, Bernal T. Dose-intensive chemotherapy including rituximab in Burkitt's leukemia or lymphoma regardless of human immunodeficiency virus infection status: final results of a phase 2 study (Burkimab). Cancer. 2013 May 1;119(9):1660-8. Epub 2013 Jan 29. [https://doi.org/10.1002/cncr.27918 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23361927 PubMed] NCT00388193
+
#Miller VA, Krug LM, Ng KK, Pizzo B, Perez W, Heelan RT, Kris MG. Phase II trial of docetaxel and vinorelbine in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Mar;18(6):1346-50. [https://doi.org/10.1200/JCO.2000.18.6.1346 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10715307 PubMed]
−
 
+
==Gemcitabine & Paclitaxel {{#subobject:29305d|Regimen=1}}==
−
==R-CODOX-M {{#subobject:89ebce|Regimen=1}}==
+
GT: '''<u>G</u>'''emcitabine & '''<u>T</u>'''axol (Paclitaxel)
−
R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:310936|Variant=1}}===
+
===Regimen variant #1, 1000/125 {{#subobject:b3708b|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2002.12.112 Kosmidis et al. 2002]
 +
|1998-2000
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdm430 Kosmidis et al. 2007]
 +
|2000-2004
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdl396 Comella et al. 2006 (SICOG 0101)]
 +
|2001-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Gemcitabine_.26_Vinorelbine|GV]]<br> 2. [[Stub#PGT|PGT]]<br> 3. [[Stub#PGV|PGV]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Paclitaxel (Taxol)]] 125 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 1000/200 {{#subobject:b9275b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdq445 Kosmidis et al. 2010]
 +
|2004-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Paclitaxel_.26_Vinorelbine_99|Paclitaxel & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. [https://doi.org/10.1093/annonc/mdm430 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17938425 PubMed]
 +
#'''SICOG 0101:''' Comella P, Filippelli G, De Cataldis G, Massidda B, Frasci G, Maiorino L, Putzu C, Mancarella S, Palmeri S, Cioffi R, Roselli M, Buzzi F, Milia V, Gambardella A, Natale D, Bianco M, Ghiani M, Masullo P; Southern Italy Cooperative Oncology Group. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann Oncol. 2007 Feb;18(2):324-30. Epub 2006 Oct 27. [https://doi.org/10.1093/annonc/mdl396 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17071935 PubMed]
 +
#Kosmidis PA, Fountzilas G, Eleftheraki AG, Kalofonos HP, Pentheroudakis G, Skarlos D, Dimopoulos MA, Bafaloukos D, Pectasides D, Samantas E, Boukovinas J, Lambaki S, Katirtzoglou N, Bakogiannis C, Syrigos KN; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus paclitaxel and vinorelbine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2011 Apr;22(4):827-34. Epub 2010 Sep 29. [https://doi.org/10.1093/annonc/mdq445 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20880999 PubMed] ACTRN12609000946213
 +
==Gemcitabine & Vinorelbine {{#subobject:3c6eb0|Regimen=1}}==
 +
VG: '''<u>V</u>'''inorelbine & '''<u>G</u>'''emcitabine
 +
<br>GV: '''<u>G</u>'''emcitabine & '''<u>V</u>'''inorelbine
 +
<br>G+V: '''<u>G</u>'''emcitabine & '''<u>V</u>'''inorelbine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 1000/25, 2 weeks out of 3 (IV vinorelbine) {{#subobject:a01f58|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2004.10.576 Laack et al. 2004]
 +
|1999-2001
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[Stub#GVP|GVP]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[http://www.lungcancerjournal.info/article/S0169-5002(05)00119-4 Tan et al. 2005 (GLOB 2)]
 +
|2000-2002
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Vinorelbine|Carboplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
====Supportive therapy====
 +
*"[[:Category:Emesis_prevention|Antiemetic]] agents and other supportive treatments were provided at the discretion of the treating physician."
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 1000/25, 3 weeks out of 4 (IV vinorelbine) {{#subobject:2c7f61|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.clinical-lung-cancer.com/article/S1525-7304(11)70825-7/pdf Greco et al. 2007 (SCRI LUN 54)]
 +
|1998-2005
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#PCG_.28Carboplatin.29|PCG]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
| style="background-color:#1a9850" |Less toxic
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 1000/60 (PO vinorelbine) {{#subobject:c8251a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405221/ Fløtten et al. 2012]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Carboplatin_.26_Vinorelbine|Carboplatin & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 60 mg/m<sup>2</sup> PO once per day on days 1 & 8
 +
'''21-day cycle for 3 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 1200/30 {{#subobject:c8uv1a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(01)00392-0 Frasci et al. 2001]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, DeCataldis G, Belli M, Iannelli N, Massidda B, Mascia V, Comella G, De Lena M; Southern Italy Cooperative Oncology Group. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer: a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer. 2001 Dec;34 Suppl 4:S65-9. [https://www.lungcancerjournal.info/article/S0169-5002(01)00392-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11742706 PubMed]
 +
#'''NCIC-CTG BR.14:''' Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. [https://doi.org/10.1200/JCO.2003.06.099 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12837810 PubMed] NCT00004100
 +
#Laack E, Dickgreber N, Müller T, Knuth A, Benk J, Lorenz C, Gieseler F, Dürk H, Engel-Riedel W, Dalhoff K, Kortsik C, Graeven U, Burk M, Dierlamm T, Welte T, Burkholder I, Edler L, Hossfeld DK; German and Swiss Lung Cancer Study Group. Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group. J Clin Oncol. 2004 Jun 15;22(12):2348-56. [https://doi.org/10.1200/JCO.2004.10.576 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15197195 PubMed]
 +
#'''GLOB 2:''' Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. [http://www.lungcancerjournal.info/article/S0169-5002(05)00119-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16022917 PubMed]
 +
#'''SCRI LUN 54:''' Greco FA, Spigel DR, Kuzur ME, Shipley D, Gray JR, Thompson DS, Burris HA, Yardley DA, Pati A, Webb CD, Gandhi JG, Hainsworth JD. Paclitaxel/Carboplatin/gemcitabine versus gemcitabine/vinorelbine in advanced non-small-cell lung cancer: a phase II/III study of the Minnie Pearl Cancer Research Network. Clin Lung Cancer. 2007 Sep;8(8):483-7. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)70825-7/pdf link to original article] [https://pubmed.ncbi.nlm.nih.gov/17922972 PubMed] NCT00193362
 +
#Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. [https://www.nature.com/articles/bjc2012284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3405221/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22759880 PubMed] NCT00737867
 +
==Ipilimumab & Nivolumab {{#subobject:517ff0|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:3a481c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1056/NEJMoa1801946 Hellmann et al. 2018 (CheckMate 227)]
 +
|rowspan=2|2015-2016
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1. [[#Nivolumab_monotherapy|Nivolumab]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Regimen_classes#Platinum_doublet|Platinum doublet]]
 +
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 17.1 vs 14.9 mo
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2019 update. Note that the proportional hazards assumption was not met; HR is therefore not reported here.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*PD-L1 expression of 1% or more
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Ipilimumab (Yervoy)]] 1 mg/kg IV once on day 1
 +
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once per day on days 1, 15, 29
 +
'''42-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''CheckMate 227:''' Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. [https://doi.org/10.1056/NEJMoa1801946 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29658845 PubMed] NCT02477826
 +
##'''Update:''' Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. Epub 2019 Sep 28. [https://doi.org/10.1056/NEJMoa1910231 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31562796 PubMed]
 +
==Nivolumab monotherapy {{#subobject:PYR1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:PYV1|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1613493 Carbone et al. 2017 (CheckMate 026)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[Regimen_classes#Platinum_doublet|Platinum doublet]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|}
 +
''Note: control arm patients in CheckMate 026 received investigator's choice of platinum doublet; the most commonly used regimen was [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|carboplatin & paclitaxel]].''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 +
**Notably, on 9/13/16 the [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm520871.htm FDA recommended] that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.
 +
'''14-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''CheckMate 026:''' Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426. [https://doi.org/10.1056/NEJMoa1613493 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28636851 PubMed] NCT02041533
 +
#'''CheckMate 227:''' Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. [https://doi.org/10.1056/NEJMoa1801946 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29658845 PubMed] NCT02477826
 +
==PCG (Carboplatin) {{#subobject:45t1c7|Regimen=1}}==
 +
PCG: '''<u>P</u>'''aclitaxel, '''<u>C</u>'''arboplatin, '''<u>G</u>'''emcitabine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:dre1ab|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2005.03.2722 Paccagnella et al. 2006]
 +
|1998-2004
 +
| style="background-color:#1a9851" |Phase 2/3 (E-esc)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_5|CP]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1, '''given second'''
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 to 60 minutes once per day on days 1 & 8, '''given third'''
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] 16 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
 +
*[[Diphenhydramine (Benadryl)]] 50 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
 +
*[[Ranitidine (Zantac)]] (or equivalent) 50 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
 +
'''21-day cycle for at least 6 cycles'''
 +
</div></div>
 +
===References===
 +
#Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. [https://doi.org/10.1200/jco.2005.03.2722 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16446341/ PubMed]
 +
==Pembrolizumab monotherapy {{#subobject:430dc7|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:d2e0ab|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1501824 Garon et al. 2015 (KEYNOTE-001)]
 +
|2012-2014
 +
| style="background-color:#91cf61" |Phase 1, >20 pts in dosing cohort
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1. [[#Carboplatin_.26_Gemcitabine_.28GCb.29| Carboplatin & Gemcitabine]]<br> 2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5| Carboplatin & Paclitaxel]]<br> 3. [[#Carboplatin_.26_Pemetrexed | Carboplatin & Pemetrexed]]<br> 4. [[#Cisplatin_.26_Gemcitabine_.28GC.29_3| Cisplatin & Gemcitabine]]<br> 5. [[#Cisplatin_.26_Pemetrexed_2| Cisplatin & Pemetrexed]]
 +
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 26.3 vs 13.4 mo<br>(HR 0.62, 95% CI 0.48-0.81)
 +
| style="background-color:#1a9850" |Superior HRQoL
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(18)32409-7 Mok et al. 2019 (KEYNOTE-042)]
 +
|2014-2017
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_5| Carboplatin & Paclitaxel]]<br> 2. [[#Carboplatin_.26_Pemetrexed_2| Carboplatin & Pemetrexed]]
 +
| style="background-color:#1a9850" |Superior OS<sup>2</sup><br>Median OS: 16.7 vs 12.1 mo<br>(HR 0.81, 95% CI 0.71-0.93)
 +
|
 +
|-
 +
|[https://doi.org/10.1200/jco.20.03579 Boyer et al. 2021 (KEYNOTE-598)]
 +
|2018-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Ipilimumab_.26_Pembrolizumab_99|Ipilimumab & Pembrolizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 +
|
 +
|-
 +
|Awaiting publication (INTR@PID Lung 037)
 +
|2018-2021
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Bintrafusp_alfa_monotherapy_77|Bintrafusp alfa]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|
 +
|-
 +
|Awaiting publication (LEAP-007)
 +
|2019-2021
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Lenvatinib_.26_Pembrolizumab|Lenvatinib & Pembrolizumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|
 +
|-
 +
|Awaiting publication (AdvanTIG-302)
 +
|2021-2025
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Ociperlimab_.26_Tislelizumab_77|Ociperlimab & Tislelizumab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|
 +
|-
 +
|Awaiting publication (MK-7684A-003)
 +
|2021-2026
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pembrolizumab_.26_Vibostolimab_77|Pembrolizumab & Vibostolimab]]
 +
| style="background-color:#d3d3d3" |TBD
 +
|
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy for KEYNOTE-024 is based on the 2021 update.''<br>
 +
''<sup>2</sup>Reported efficacy for KEYNOTE-042 is for the population with TPS of 1% or more.''<br>
 +
''KEYNOTE-024 treatment choice for patients in the comparator arm was up to the investigators; most with nonsquamous histology received carboplatin & pemetrexed, whereas most with squamous histology received carboplatin & gemcitabine. Patients could receive a maximum of 35 cycles. ORR was 45% (95% CI: 37-53).''
 +
<br>''KEYNOTE-042 treatment choice for patients in the comparator arm was carboplatin & paclitaxel for patients with squamous histology, and carboplatin & pemetrexed for patients with nonsquamous histology.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Biomarker eligibility criteria====
 +
*KEYNOTE-024: PD-L1 to be expressed on at least '''50% of tumor cells''', no EGFR/ALK mutations
 +
*KEYNOTE-042: PD-L1 to be expressed on at least '''1% of tumor cells'''
 +
*KEYNOTE-598: PD-L1 TPS of 50% or more; no sensitizing EGFR or ALK mutations
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 +
'''21-day cycle for up to 35 cycles'''
 +
</div></div>
 +
===References===
 +
#'''KEYNOTE-001:''' Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. [https://doi.org/10.1056/NEJMoa1501824 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25891174 PubMed] NCT01295827
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
<!-- # '''Abstract:''' Tony Mok, Yi-Long Wu, Patricia A, Watson, Jin Zhang, Reshma A. Rangwala, and Gilberto Lopes. Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology 2015 33:15_suppl, TPS8105-TPS8105 [https://doi.org/10.1200/jco.2015.33.15_suppl.tps8105 link to abstract] -->
 +
#'''KEYNOTE-042:''' Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. [https://doi.org/10.1016/S0140-6736(18)32409-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30955977 PubMed] NCT02220894
 +
#'''KEYNOTE-598:''' Boyer M, Şendur MAN, Rodríguez-Abreu D, Park K, Lee DH, Çiçin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jul 20;39(21):2327-2338. Epub 2021 Jan 29. [https://doi.org/10.1200/jco.20.03579 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33513313/ PubMed] NCT03302234
 +
#'''AdvanTIG-302:''' NCT04746924
 +
#'''INTR@PID Lung 037:''' NCT03631706
 +
#'''LEAP-007:''' NCT03829332
 +
#'''MK-7684A-003:''' NCT04738487
 +
=Advanced or metastatic disease, first-line, elderly or poor performance status=
 +
==Carboplatin & Gemcitabine (GCb) {{#subobject:2f045e|Regimen=1}}==
 +
CG: '''<u>C</u>'''arboplatin & '''<u>G</u>'''emcitabine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:c4b462|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdq637 Biesma et al. 2011 (NVALT-3)]
 +
|2003-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_6|CP]]
 +
|
 +
| style="background-color:#ffffbf" |Similar QoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div>
 +
===References===
 +
#'''NVALT-3:''' Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. [https://doi.org/10.1093/annonc/mdq637 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21252061 PubMed] NTR925
 +
==Carboplatin & Paclitaxel (CP) {{#subobject:050d96|Regimen=1}}==
 +
TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin
 +
<br>CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 5/175 {{#subobject:5dd7ea|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 17%" |Study
 +
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdq637 Biesma et al. 2011 (NVALT-3)]
 +
|2003-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_4|CG]]
 +
|
 +
| style="background-color:#ffffbf" |Similar QoL
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 6/90 {{#subobject:bd42df|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(11)60780-0 Quoix et al. 2011 (IFCT-0501)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Gemcitabine_monotherapy|Gemcitabine]]<br>2. [[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.3 vs 6.2 mo<br>(HR 0.64, 95% CI 0.52-0.78)
 +
|-
 +
|}
 +
''Study involved only patients 70 to 89 years old''
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
====Supportive therapy====
 +
*Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3-4 neutropenia
 +
'''28-day cycle for up to 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 6/200 {{#subobject:7ba15a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2007.13.2720 Lilenbaum et al. 2008]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Erlotinib_monotherapy_99|Erlotinib]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 6/225 {{#subobject:e1af15|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://link.springer.com/article/10.1007/s12185-010-0728-0 Maruyama et al. 2010]
+
|[https://www.jto.org/article/S1556-0864(15)31485-4 Langer et al. 2008]
−
|style="background-color:#ffffbe"|Pilot, <20 pts
+
|2002-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_poliglumex_77|Carboplatin & PPX]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/124/19/2913.long Jacobson et al. 2014]
+
|}
−
|style="background-color:#ffffbe"|Expert Recommendation
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 +
*[[Paclitaxel (Taxol)]] 225 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. [https://doi.org/10.1200/jco.2007.13.2720 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18281658 PubMed]
 +
#Langer CJ, O'Byrne KJ, Socinski MA, Mikhailov SM, Leśniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6):623-30. [https://www.jto.org/article/S1556-0864(15)31485-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18520802 PubMed]
 +
#'''NVALT-3:''' Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. [https://doi.org/10.1093/annonc/mdq637 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21252061 PubMed] NTR925
 +
#'''IFCT-0501:''' Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [https://doi.org/10.1016/S0140-6736(11)60780-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21831418 PubMed] NCT00298415
 +
==Carboplatin & Pemetrexed {{#subobject:fc1ec6|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Carboplatin (Paraplatin) and Pemetrexed (Alimta) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:b1cc1a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.48.1911 Zukin et al. 2013 (INCA-Lung001)]
 +
|2008-2011
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Pemetrexed_monotherapy|Pemetrexed]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 9.3 vs 5.3 mo<br>(HR 0.62, 95% CI 0.46-0.83)
 
|-
 
|-
 
|}
 
|}
−
''Note: In the Jacobson et al. 2014 review, the authors describe a "Modified Magrath regimen of R-CODOX/R-IVAC" based on the timing and dosage of [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004]. However, [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004] did not include rituximab in the schema. Others have published retrospective series of this regimen; doses here are based on the review article. This is for low-risk patients (i.e., single site of disease less than 10 cm with normal LDH).''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
 +
====Supportive therapy====
 +
*(Ardizzoni et al. 2012 contained more details):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycle for up to 4 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2012. -->
 +
#'''INCA-Lung001:''' Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [https://doi.org/10.1200/jco.2012.48.1911 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23775961 PubMed] NCT01836575
 +
==Carboplatin, Pemetrexed, Bevacizumab {{#subobject:03239b|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:8a4c4f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1002/cncr.30986 Spigel et al. 2018 (ToPPS)]
 +
|2009-2013
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|1. [[#Pemetrexed_monotherapy|Pemetrexed]]<br> 2. [[#Pemetrexed_.26_Bevacizumab|Pemetrexed & Bevacizumab]]
 +
|PFS: 4.8 mo
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] as follows:
 +
**Cycles 1 to 4: AUC 5 IV once on day 1
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] as follows:
+
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once no earlier than day 3
+
====Supportive therapy====
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day 1
+
*Premedications, [[Folic acid (Folate)]], and vitamin supplementation per standard guidelines
 +
*Antiemetics per standard guidelines
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''ToPPS:''' Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. [https://doi.org/10.1002/cncr.30986 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29451696 PubMed] NCT00892710
 +
==Cisplatin & Gemcitabine (GC) {{#subobject:21a22f|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:b72a5d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(13)00155-4 Morabito et al. 2013 (CAPPA-2)]
 +
|2008-2012
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 5.9 vs 3 mo<br>(HR 0.52, 95% CI 0.28-0.98)
 +
|-
 +
|[https://doi.org/10.1200/JCO.2017.76.8390 Gridelli et al. 2018 (MILES-3)]
 +
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2017.76.8390 Gridelli et al. 2018 (MILES-4)]
 +
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''MILES studies involved only patients at least 70 years old. CAPPA-2 allowed patients aged 18-70 with ECOG PS = 2.''
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Cisplatin (Platinol)]]
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 15
+
*[[Gemcitabine (Gemzar)]]
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+
</div></div>
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 2 to 4 hours once on day 15
+
===References===
−
====CNS therapy, prophylaxis====
+
#'''CAPPA-2:''' Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. [https://www.lungcancerjournal.info/article/S0169-5002(13)00155-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23643177 PubMed] NCT00526643
−
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 1
+
#'''MILES-3:''' Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2017.76.8390 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30028656 PubMed] NCT01405586
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 1
+
#'''MILES-4:''' Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2017.76.8390 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30028656 PubMed] NCT01656551
−
====CNS therapy, treatment (for CSF positive)====
+
==Docetaxel monotherapy {{#subobject:17ba7f|Regimen=1}}==
−
*Treatment as per CNS prophylaxis PLUS in cycle 1 only:
+
===Example orders===
−
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 5
+
*[[Example orders for Docetaxel (Taxotere) in non-small cell lung cancer]]
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 25 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:22a876|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://academic.oup.com/jjco/article/45/1/88/889067 Tsukada et al. 2014 (JCOG0207)]
 +
|2003-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Docetaxel_.28DC.29_99|Cisplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 36 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:110876|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1002/cncr.23019 Hainsworth et al. 2007]
 +
|2001-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Docetaxel_.26_Gemcitabine|Docetaxel & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 36 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 38 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:75b593|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.clinical-lung-cancer.com/article/S1525-7304(11)00016-7 Karampeazis et al. 2011 (HORG CT/03.07)]
 +
|2003-2008
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 38 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #4, 60 mg/m<sup>2</sup> q3wk {{#subobject:afca35|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2006.06.1044 Kudoh et al. 2006 (WJTOG 9904)]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2014.55.8627 Abe et al. 2015 (JCOG0803/WJOG4307L)]
 +
|2008-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Docetaxel_.28DC.29_99|Cisplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
'''21-day cycle for up to 4 cycles (WJTOG 9904) or indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''WJTOG 9904:''' Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. [https://doi.org/10.1200/JCO.2006.06.1044 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16877734 PubMed] NCT00148291
 +
#Hainsworth JD, Spigel DR, Farley C, Shipley DL, Bearden JD, Gandhi J, Houston GA, Greco FA. Weekly docetaxel versus docetaxel/gemcitabine in the treatment of elderly or poor performance status patients with advanced nonsmall cell lung cancer: a randomized phase 3 trial of the Minnie Pearl Cancer Research Network. Cancer. 2007 Nov 1;110(9):2027-34. [https://doi.org/10.1002/cncr.23019 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17823908 PubMed]
 +
#'''HORG CT/03.07:''' Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)00016-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21663857 PubMed] NCT00441922
 +
#'''JCOG0207:''' Tsukada H, Yokoyama A, Goto K, Shinkai T, Harada M, Ando M, Shibata T, Ohe Y, Tamura T, Saijo N; Lung Cancer Study Group of the Japan Clinical Oncology Group (JCOG). Randomized controlled trial comparing docetaxel-cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small-cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207. Jpn J Clin Oncol. 2015 Jan;45(1):88-95. Epub 2014 Nov 6. [https://academic.oup.com/jjco/article/45/1/88/889067 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25378648 PubMed] UMIN C000000146
 +
#'''JCOG0803/WJOG4307L:''' Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Mizusawa J, Shibata T, Nakamura S, Ando M, Yokoyama A, Nakagawa K, Saijo N, Tamura T. Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol. 2015 Feb 20;33(6):575-81. Epub 2015 Jan 12. [https://doi.org/10.1200/JCO.2014.55.8627 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25584004 PubMed] UMIN000001424
 +
==Gemcitabine monotherapy {{#subobject:21a88f|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 1000 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:137c9f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.jto.org/article/S1556-0864(15)33345-1 O'Brien et al. 2008]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Paclitaxel_poliglumex_monotherapy_77|Paclitaxel poliglumex]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 1150 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:340c10|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(11)60780-0 Quoix et al. 2011 (IFCT-0501)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_6|Carboplatin & Paclitaxel]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
''Study involved only patients 70 to 89 years old''
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1150 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
====Supportive therapy====
 +
*Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia
 +
'''21-day cycle for up to 5 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 1200 mg/m<sup>2</sup>, 2 out of 3 weeks {{#subobject:b8de5d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
 +
|rowspan=2|1997-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Gemcitabine_.26_Vinorelbine_2|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793001/ Reynolds et al. 2009 (USO-03012)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29_2|Carboplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(13)00155-4 Morabito et al. 2013 (CAPPA-2)]
 +
|2008-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_6|Cisplatin & Gemcitabine]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2017.76.8390 Gridelli et al. 2018 (MILES-3)]
 +
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_6|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2017.76.8390 Gridelli et al. 2018 (MILES-4)]
 +
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cisplatin_.26_Gemcitabine_.28GC.29_6|Cisplatin & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''MILES studies involved only patients at least 70 years old. CAPPA-2 allowed patients aged 18-70 with ECOG PS = 2.''
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
====Supportive therapy====
 +
*"[[:Category:Emesis_prevention|Antiemetic]] agents and other supportive treatments were provided at the discretion of the treating physician."
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div></div>
 +
===References===
 +
#'''MILES:''' Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12618501 PubMed] NCT00003447
 +
#'''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://www.nature.com/articles/6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15266334 PubMed]
 +
#O'Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, Hotko YS, Ganul VL, Kostinsky IY, Eisenfeld AJ, Sandalic L, Oldham FB, Bandstra B, Sandler AB, Singer JW. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):728-34. [https://www.jto.org/article/S1556-0864(15)33345-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18594318 PubMed]
 +
#'''USO-03012:''' Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, Caton JR, Demarco LC, O'Rourke MA, Shaw Wright G, Boehm KA, Asmar L, Bromund J, Peng G, Monberg MJ, Bepler G. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol. 2009 Dec 1;27(34):5808-15. Epub 2009 Nov 2. [https://doi.org/10.1200/JCO.2009.21.9766 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793001/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19884554 PubMed] NCT00190710
 +
#'''IFCT-0501:''' Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [https://doi.org/10.1016/S0140-6736(11)60780-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21831418 PubMed] NCT00298415
 +
#'''CAPPA-2:''' Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. [https://www.lungcancerjournal.info/article/S0169-5002(13)00155-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23643177 PubMed] NCT00526643
 +
#'''MILES-3:''' Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2017.76.8390 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30028656 PubMed] NCT01405586
 +
#'''MILES-4:''' Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2017.76.8390 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30028656 PubMed] NCT01656551
 +
#'''IPSOS:''' NCT03191786
 +
==Gemcitabine & Paclitaxel {{#subobject:fa1732|Regimen=1}}==
 +
GT: '''<u>G</u>'''emcitabine & '''<u>T</u>'''axol (Paclitaxel)
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:a80095|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ Comella et al. 2004 (SICOG 9909)]
 +
|rowspan=2|1999-2003
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Gemcitabine_monotherapy|Gemcitabine]]<br> 2. [[Non-small_cell_lung_cancer_-_historical#Paclitaxel_monotherapy|Paclitaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|3. [[#Gemcitabine_.26_Vinorelbine_2|GV]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div>
 +
===References===
 +
#'''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://www.nature.com/articles/6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15266334 PubMed]
 +
==Gemcitabine & Vinorelbine {{#subobject:0e1f07|Regimen=1}}==
 +
GV: '''<u>G</u>'''emcitabine & '''<u>V</u>'''inorelbine
 +
<br>VG: '''<u>V</u>'''inorelbine & '''<u>G</u>'''emcitabine
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 1000/25 {{#subobject:4d6b82|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
 +
|rowspan=2|1997-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*At least 70 years old
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 24 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> every 6 hours until methotrexate level undetectable
+
*"[[:Category:Emesis_prevention|Antiemetic]] agents and other supportive treatments were provided at the discretion of the treating physician."
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3
+
'''21-day cycle for up to 6 cycles'''
−
'''3 cycles'''
+
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 1200/30 {{#subobject:07e5b2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.13.2529 Frasci et al. 2000]
 +
|1997-1999
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Vinorelbine_monotherapy|Vinorelbine]]
 +
| style="background-color:#1a9850" |Superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Eligibility criteria====
 +
*At least 70 years old
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1200 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycle for up to 6 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007/s12185-010-0728-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21120644 PubMed]
+
#Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, De Cataldis G, Iannelli A, Bilancia D, Belli M, Massidda B, Piantedosi F, Comella G, De Lena M. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Jul;18(13):2529-36. [https://doi.org/10.1200/JCO.2000.18.13.2529 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10893283 PubMed]
−
# '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21339382 PubMed]
+
#'''MILES:''' Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12618501 PubMed] NCT00003447
−
# '''Review:''' Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014 Nov 6;124(19):2913-20. Epub 2014 Sep 25. [http://www.bloodjournal.org/content/124/19/2913.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25258344 PubMed]
+
#'''SICOG 9909:''' Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. [https://www.nature.com/articles/6602011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409832/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15266334 PubMed]
−
 
+
==Pemetrexed monotherapy {{#subobject:615e55|Regimen=1}}==
−
==R-CODOX-M/R-IVAC {{#subobject:2a898f|Regimen=1}}==
+
===Example orders===
−
R-CODOX-M/R-IVAC: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''orubicin, '''<u>M</u>'''ethotrexate alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+
*[[Example orders for Pemetrexed (Alimta) in non-small cell lung cancer]]
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:9e99df|Variant=1}}===
+
===Regimen {{#subobject:7f11b0|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.48.1911 Zukin et al. 2013 (INCA-Lung001)]
 +
|2008-2011
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]]
 +
| style="background-color:#d73027" |Inferior OS
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/124/19/2913.long Jacobson et al. 2014]
+
|[https://doi.org/10.1200/JCO.2017.76.8390 Gridelli et al. 2018 (MILES-4)]
−
|style="background-color:#ffffbe"|Expert Recommendation
+
|2011-2016
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Cisplatin_.26_Gemcitabine_.28GC.29_99|Cisplatin & Gemcitabine]]<br> 2. [[#Cisplatin_.26_Pemetrexed_99|Cisplatin & Pemetrexed]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
−
''Note: In the Jacobson et al. 2014 review, the authors describe a "Modified Magrath regimen of R-CODOX/R-IVAC" based on the timing and dosage of [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004]. However, [https://doi.org/10.1080/1042819031000141301 LaCasce et al. 2004] did not include rituximab in the schema. Others have published retrospective series of this regimen; doses here are based on the review article. This is for high-risk patients.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy, R-CODOX-M portion====
+
====Chemotherapy====
−
*[[Rituximab (Rituxan)]] as follows:
+
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
−
**Cycle 1: 375 mg/m<sup>2</sup> IV once no earlier than day 3
+
'''21-day cycle for up to 4 cycles (INCA-Lung001) or 6 cycles (MILES-4)'''
−
**Cycle 2 onwards: 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, R-CODOX-M portion====
 
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once per day on days 1 & 15
 
−
*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 2 to 4 hours once on day 15
 
−
====CNS therapy, prophylaxis, R-CODOX-M portion====
 
−
*[[Cytarabine (Ara-C)]] 50 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 1
 
−
====CNS therapy, treatment (for CSF positive), R-CODOX-M portion====
 
−
*Treatment as per CNS prophylaxis PLUS in cycle 1 only:
 
−
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 5
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 15
 
−
====Supportive therapy, R-CODOX-M portion====
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 24 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> every 6 hours until methotrexate level undetectable
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 3
 
−
====Targeted therapy, R-IVAC portion====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
−
====Chemotherapy, R-IVAC portion====
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis, R-IVAC portion====
 
−
*[[Methotrexate (MTX)]] 12 mg IT once on day 5
 
−
====CNS therapy, treatment (for CSF positive), R-IVAC portion====
 
−
*Treatment as per CNS prophylaxis PLUS in cycle 1 only:
 
−
*[[Cytarabine (Ara-C)]] 50 mg IT once on day 3
 
−
====Supportive therapy, R-IVAC portion====
 
−
*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> over 1 hour once per day on days 1 to 5 mixed with [[Ifosfamide (Ifex)]], then 300 mg/m<sup>2</sup> IV every four hours twice per day on days 1 to 5
 
−
*[[Pegfilgrastim (Neulasta)]] 6 mg SC once on day 6
 
−
'''Patients receive 2 cycles each of R-CODOX-M and R-IVAC (alternating)'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Maruyama D, Watanabe T, Maeshima AM, Nomoto J, Taniguchi H, Azuma T, Mori M, Munakata W, Kim SW, Kobayashi Y, Matsuno Y, Tobinai K. Modified cyclophosphamide, vincristine, doxorubicin, and methotrexate (CODOX-M)/ifosfamide, etoposide, and cytarabine (IVAC) therapy with or without rituximab in Japanese adult patients with Burkitt lymphoma (BL) and B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and BL. Int J Hematol. 2010 Dec;92(5):732-43. Epub 2010 Dec 1. [http://link.springer.com/article/10.1007/s12185-010-0728-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21120644 PubMed]
+
<!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2012. -->
−
# '''Retrospective:''' Barnes JA, Lacasce AS, Feng Y, Toomey CE, Neuberg D, Michaelson JS, Hochberg EP, Abramson JS. Evaluation of the addition of rituximab to CODOX-M/IVAC for Burkitt's lymphoma: a retrospective analysis. Ann Oncol. 2011 Aug;22(8):1859-64. Epub 2011 Feb 21. [https://doi.org/10.1093/annonc/mdq677 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21339382 PubMed]
+
#'''INCA-Lung001:''' Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [https://doi.org/10.1200/jco.2012.48.1911 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23775961 PubMed] NCT01836575
−
# '''Review:''' Jacobson C, LaCasce A. How I treat Burkitt lymphoma in adults. Blood. 2014 Nov 6;124(19):2913-20. Epub 2014 Sep 25. [http://www.bloodjournal.org/content/124/19/2913.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25258344 PubMed]
+
#'''ToPPS:''' Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. [https://doi.org/10.1002/cncr.30986 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29451696 PubMed] NCT00892710
−
==R-CODOX-M (Pegylated liposomal doxorubicin substituted) {{#subobject:9a2bc1|Regimen=1}}==
+
#'''MILES-4:''' Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2017.76.8390 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30028656 PubMed] NCT01656551
−
R-CODOX-M: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''il (Pegylated liposomal doxorubicin), '''<u>M</u>'''ethotrexate
+
==Pemetrexed & Bevacizumab {{#subobject:3c119a|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:de5687|Variant=1}}===
+
===Regimen {{#subobject:e31aed|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
!style="width: 20%"|Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841019/ Evens et al. 2013 (NU 06H2)]
+
|[https://doi.org/10.1002/cncr.30986 Spigel et al. 2018 (ToPPS)]
−
|style="background-color:#91cf61"|Phase 2
+
|2009-2013
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|1. [[#Pemetrexed_monotherapy|Pemetrexed]]<br> 2. [[#Carboplatin.2C_Pemetrexed.2C_Bevacizumab_2|Carboplatin, Pemetrexed, Bevacizumab]]
 +
|PFS: 4.0 mo
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen is for low-risk patients.''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1
 
====Targeted therapy====
 
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once per day on days 0 & 8
+
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
 +
====Supportive therapy====
 +
*Premedications, [[Folic acid (Folate)]], and vitamin supplementation per standard guidelines
 +
*Antiemetics per standard guidelines
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''ToPPS:''' Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. [https://doi.org/10.1002/cncr.30986 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29451696 PubMed] NCT00892710
 +
==Vinorelbine monotherapy {{#subobject:aa0ce0|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 25 mg/m<sup>2</sup> {{#subobject:5beb7a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2006.06.1044 Kudoh et al. 2006 (WJTOG 9904)]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy|Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.clinical-lung-cancer.com/article/S1525-7304(11)00016-7 Karampeazis et al. 2011 (HORG CT/03.07)]
 +
|2003-2008
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy|Docetaxel]]
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(11)60780-0 Quoix et al. 2011 (IFCT-0501)]
 +
|2006-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Paclitaxel_.28CP.29_6|Carboplatin & Paclitaxel]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|}
 +
''IFCT-0501 involved only patients 70 to 89 years old''
 +
====Chemotherapy====
 +
*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8
 +
====Supportive therapy====
 +
*Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia
 +
'''21-day cycle for up to 4 cycles (WJTOG 9904), 5 cycles (IFCT-0501), or 6 cycles (HORG CT/03.07)'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:408bee|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[http://jnci.oxfordjournals.org/content/91/1/66.long Gridelli et al. 1999 (ELVIS)]
 +
|1996-1997
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Best_supportive_care|Best supportive care]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
| rowspan="2" |[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
 +
|rowspan=2|1997-2000
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Gemcitabine_monotherapy|Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Study involved only patients at least 70 years old''
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 60 minutes once on day 1, then 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 to 5
+
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once per day on days 1 & 8
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once on day 1
 
−
*[[Methotrexate (MTX)]] by the following criteria:
 
−
**LP: 12 mg IT once on day 3
 
−
**Ommaya reservoir: 6 mg IT once on day 3
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 36 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
+
*(varies depending on reference):
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 6 & 7, then on day 14 onwards until ANC greater than 1500/uL
+
*ELVIS: [[Metoclopramide (Reglan)]] 20 mg IV bolus once per day on days 1 & 8, prior to [[Vinorelbine (Navelbine)]]
−
'''3 cycles (length not specified)'''
+
*MILES: "[[:Category:Emesis_prevention|Antiemetic]] agents and other supportive treatments were provided at the discretion of the treating physician."
 +
'''21-day cycle for up to 6 cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NU 06H2:''' Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. Epub 2013 Oct 20. [https://doi.org/10.1093/annonc/mdt414 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841019/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24146219 PubMed]
+
#'''ELVIS:''' Gridelli C, Perrone F, Gallo C; Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. [http://jnci.oxfordjournals.org/content/91/1/66.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9890172 PubMed]
−
==R-CODOX-M/R-IVAC (Pegylated liposomal doxorubicin substituted) {{#subobject:4ba54c|Regimen=1}}==
+
#'''MILES:''' Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12618501 PubMed] NCT00003447
−
R-CODOX-M/R-IVAC: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>DOX</u>'''il (Pegylated liposomal doxorubicin), '''<u>M</u>'''ethotrexate alternating with '''<u>R</u>'''ituximab, '''<u>I</u>'''fosfamide, '''<u>V</u>'''epesid (Etoposide), '''<u>A</u>'''ra-'''<u>C</u>''' (Cytarabine)
+
#'''WJTOG 9904:''' Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. [https://doi.org/10.1200/JCO.2006.06.1044 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16877734 PubMed] NCT00148291
 +
#'''HORG CT/03.07:''' Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)00016-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21663857 PubMed] NCT00441922
 +
#'''IFCT-0501:''' Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [https://doi.org/10.1016/S0140-6736(11)60780-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21831418 PubMed] NCT00298415
 +
#'''IPSOS:''' NCT03191786
 +
=Maintenance after first-line therapy=
 +
==Bevacizumab monotherapy {{#subobject:75f589|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:92910b|Variant=1}}===
+
===Regimen {{#subobject:e01dd1|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 17%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 15%" |Years of enrollment
 +
! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 17%" |Comparator
 +
! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841019/ Evens et al. 2013 (NU 06H2)]
+
|[https://doi.org/10.1200/JCO.2012.47.3983 Johnson et al. 2013 (ATLAS-NSCLC)]
−
|style="background-color:#91cf61"|Phase 2
+
|2006-2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Erlotinib_.26_Bevacizumab_88|Erlotinib & Bevacizumab]] maintenance
 +
| style="background-color:#d73027" |Inferior PFS<sup>1</sup>
 +
| style="background-color:#1a9850" |Less toxic
 
|-
 
|-
 
|}
 
|}
−
''Note: This protocol is for high-risk patients.''
+
''<sup>1</sup>While this arm was inferior in ATLAS, the authors note that, due to toxicity, the "two-drug maintenance regimen will not lead to a new postchemotherapy standard of care."''<br>
 +
''Note: This trial should not be confused with the ones with the same name in breast cancer and in renal cell carcinoma.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Carboplatin.2C_Docetaxel.2C_Bevacizumab_88|Carboplatin, Docetaxel, Bevacizumab]] x 4 or [[#Carboplatin.2C_Gemcitabine.2C_Bevacizumab_88|Carboplatin, Gemcitabine, Bevacizumab]] x 4 or [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Bevacizumab|PacCBev]] x 4 or Cisplatin, Docetaxel, Bevacizumab x 4 or [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Bevacizumab|Cisplatin, Gemcitabine, Bevacizumab]] x 4 or Cisplatin, Vinorelbine, Bevacizumab x 4
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy, R-CODOX-M portion====
+
====Targeted therapy====
−
*[[Rituximab (Rituxan)]] 500 mg/m<sup>2</sup> IV once per day on days 0 & 8
+
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
−
====Chemotherapy, R-CODOX-M portion====
+
'''21-day cycles'''
−
*[[Cyclophosphamide (Cytoxan)]] 800 mg/m<sup>2</sup> IV over 60 minutes once on day 1, then 200 mg/m<sup>2</sup> IV over 60 minutes once per day on days 2 to 5
 
−
*[[Vincristine (Oncovin)]] 1.5 mg/m<sup>2</sup> (maximum dose of 2 mg) IV push once per day on days 1 & 8
 
−
*[[Pegylated liposomal doxorubicin (Doxil)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Methotrexate (MTX)]] 300 mg/m<sup>2</sup> IV over 60 minutes once on day 10, then 2700 mg/m<sup>2</sup> IV continuous infusion over 23 hours (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis, R-CODOX-M portion====
 
−
*[[Cytarabine (Ara-C)]] 70 mg IT once per day on days 1 & 3
 
−
*[[Methotrexate (MTX)]] 12 mg IT (or 6 mg into Ommaya) once on day 15
 
−
====Supportive therapy, R-CODOX-M portion====
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once 36 hours after start of IV methotrexate, then 15 mg/m<sup>2</sup> IV every 6 hours until methotrexate level is less than 50 nmol/L
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 6 & 7, then on day 14 onwards until ANC greater than 1500/uL
 
−
====Targeted therapy, R-IVAC portion====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 0 & either 6 or 7
 
−
====Chemotherapy, R-IVAC portion====
 
−
*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV over 3 hours once per day on days 1 to 5
 
−
*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5
 
−
*[[Cytarabine (Ara-C)]] 2000 mg/m<sup>2</sup> IV over 3 hours every 12 hours on days 1 & 2 (total dose per cycle: 8000 mg/m<sup>2</sup>)
 
−
====CNS therapy, prophylaxis, R-IVAC portion====
 
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 5
 
−
====Supportive therapy, R-IVAC portion====
 
−
*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> mixed with first [[Ifosfamide (Ifex)]], then 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours (total dose per cycle: 5500 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 15 mg PO every 6 hours on day 6, starting 24 hours after intrathecal [[Methotrexate (MTX)]] (total dose per cycle: 60 mg)
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on either day 6 or 7 and continuing until ANC greater than 1500/uL
 
−
'''Four alternating cycles of R-CODOX-M & R-IVAC'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''NU 06H2:''' Evens AM, Carson KR, Kolesar J, Nabhan C, Helenowski I, Islam N, Jovanovic B, Barr PM, Caimi PF, Gregory SA, Gordon LI. A multicenter phase II study incorporating high-dose rituximab and liposomal doxorubicin into the CODOX-M/IVAC regimen for untreated Burkitt's lymphoma. Ann Oncol. 2013 Dec;24(12):3076-81. Epub 2013 Oct 20. [https://doi.org/10.1093/annonc/mdt414 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841019/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24146219 PubMed]
+
#'''ATLAS:''' Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34. Epub 2013 Oct 7. [https://doi.org/10.1200/JCO.2012.47.3983 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/24101054 PubMed] NCT00257608
−
==R-COPADM {{#subobject:c6bb81|Regimen=1}}==
+
==Docetaxel monotherapy {{#subobject:gzbz99|Regimen=1}}==
−
R-COPADM: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>AD</u>'''riamycin (Doxorubicin), '''<u>M</u>'''ethotrexate
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:85f5b8|Variant=1}}===
+
===Regimen {{#subobject:cy1gd7|Variant=1}}===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
Line 889: Line 5,351:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1016/S0140-6736(15)01317-3 Ribrag et al. 2016 (LMBA-02)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7944306/ Zhang et al. 2021 (TFINE)]
−
|2004-2010
+
|2009-2011
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
 
|style="background-color:#1a9851"|Phase 3 (E-esc)
−
|[[#COPADM|COPADM]]
+
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation_3|Observation]]
−
|style="background-color:#91cf60"|Seems to have superior EFS
+
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 5.8 vs 3 mo<br>(HR 0.57, 95% CI 0.40-0.80)
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement); see manuscript for details about the regimen for group C.''
 
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#CVP|COP prephase]]
+
*[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|DC]]; DC60 x 4 versus [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_.28DC.29_3|DC]]; DC75 x 4
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 0 & 6
 
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup>/day IV on days 2 to 4
+
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
'''21-day cycle for up to 6 cycles'''
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
+
</div></div>
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV once on day 1
+
===References===
−
====Glucocorticoid therapy====
+
# ''TFINE:''' Zhang L, Lu S, Cheng Y, Hu Z, Wu YL, Chen Z, Chen G, Liu X, Yang J, Zhang L, Chen J, Huang M, Tao M, Cheng G, Huang C, Zhou C, Zhang W, Zhao H, Sun Y. Docetaxel maintenance therapy versus best supportive care after first-line chemotherapy with different dose docetaxel plus cisplatin for advanced non-small cell lung cancer (TFINE study, CTONG-0904): an open-label, randomized, phase III trial. Ann Transl Med. 2021 Feb;9(4):338. [https://doi.org/10.21037/atm-20-8078 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7944306/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33708965/ PubMed] NCT01038661
−
*[[Prednisolone (Millipred)]] 60 mg/m<sup>2</sup>/day IV or PO on days 1 to 5
+
==Gemcitabine monotherapy {{#subobject:5d1f99|Regimen=1}}==
−
====Supportive therapy====
+
<div class="toccolours" style="background-color:#eeeeee">
−
*[[Folinic acid (Leucovorin)]] (dose/route not specified) on days 2 to 6
+
===Regimen {{#subobject:ce1f77|Variant=1}}===
−
====CNS therapy, prophylaxis====
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
*[[Methotrexate (MTX)]] 15 mg IT once per day on days 2 & 6
+
!style="width: 20%"|Study
−
*[[Hydrocortisone (Cortef)]] (dose not specified) IT once per day on days 2 & 6 (admixed with MTX)
+
!style="width: 20%"|Years of enrollment
−
'''2 cycles (length not specified)'''
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(06)00060-2 Brodowicz et al. 2006]
 +
|1999-2002
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Observation_3|Observation]]
 +
| style="background-color:#1a9850" |Superior TTP
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/JCO.2011.39.9782 Pérol et al. 2012 (IFCT-GFPC 0502)]
 +
|rowspan=2|2006-2009
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|1. [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy|Erlotinib]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer_-_null_regimens#Observation_3|Observation]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 3.8 vs 1.9 mo<br>(HR 0.56, 95% CI 0.44-0.72)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Cisplatin_.26_Gemcitabine_.28GC.29_3|Cisplatin & Gemcitabine]] x 4
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#cbd5e7">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Subsequent treatment====
+
====Chemotherapy====
−
*[[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] consolidation
+
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMBA-02:''' Ribrag V, Koscielny S, Bosq J, Leguay T, Casasnovas O, Fornecker LM, Recher C, Ghesquieres H, Morschhauser F, Girault S, Le Gouill S, Ojeda-Uribe M, Mariette C, Cornillon J, Cartron G, Verge V, Chassagne-Clément C, Dombret H, Coiffier B, Lamy T, Tilly H, Salles G. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016 Jun 11;387(10036):2402-11. Epub 2016 Apr 11. [https://doi.org/10.1016/S0140-6736(15)01317-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27080498 PubMed] NCT00180882
+
#Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, Ciuleanu T, Cucevic B, Gyurkovits K, Ulsperger E, Jassem J, Grgic M, Saip P, Szilasi M, Wiltschke C, Wagnerova M, Oskina N, Soldatenkova V, Zielinski C, Wenczl M; Central European Cooperative Oncology Group. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006 May;52(2):155-63. Epub 2006 Mar 29. [https://www.lungcancerjournal.info/article/S0169-5002(06)00060-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16569462 PubMed]
−
==R-Hyper-CVAD/R-MA {{#subobject:6b7f66|Regimen=1}}==
+
#'''IFCT-GFPC 0502:''' Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. [https://doi.org/10.1200/JCO.2011.39.9782 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22949150 PubMed] NCT00300586
−
R-Hyper-CVAD/R-MA: '''<u>R</u>'''ituximab, '''<u>Hyper</u>'''fractionated '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>D</u>'''examethasone altenating with '''<u>R</u>'''ituximab, '''<u>M</u>'''ethotrexate, '''<u>A</u>'''ra-C (Cytarabine)
+
==Ipilimumab monotherapy {{#subobject:b19c3f|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:1ae302|Variant=1}}===
+
===Regimen {{#subobject:b4472a|Variant=1}}===
 
{| class="wikitable" style="width: 40%; text-align:center;"  
 
{| class="wikitable" style="width: 40%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 25%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://doi.org/10.1002/cncr.21776 Thomas et al. 2006]
+
|[https://doi.org/10.1200/jco.2011.38.4032 Lynch et al. 2012 (CA184-041)]
−
|style="background-color:#ffffbe"|Pilot, <20 pts
+
| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|Carboplatin, Paclitaxel, Ipilimumab]] x 6
 +
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy, Part A====
+
====Immunotherapy====
−
*[[Rituximab (Rituxan)]] as follows:
+
*[[Ipilimumab (Yervoy)]] 10 mg/kg IV once on day 1
−
**Cycles 1 & 3: 375 mg/m<sup>2</sup> IV over 2 to 6 hours once per day on days 1 & 11
+
'''12-week cycles'''
−
====Chemotherapy, Part A====
 
−
*[[Cyclophosphamide (Cytoxan)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 300 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 1 to 3 (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Vincristine (Oncovin)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 2 mg IV once per day on days 4 & 11
 
−
*[[Doxorubicin (Adriamycin)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 50 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 4
 
−
====Glucocorticoid therapy, Part A====
 
−
*[[Dexamethasone (Decadron)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 40 mg IV or PO once per day on days 1 to 4, 11 to 14
 
−
====Supportive therapy, Part A====
 
−
*[[Mesna (Mesnex)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 600 mg/m<sup>2</sup>/day IV continuous infusion over 72 hours, started on day 1, starting 1 hour before [[Cyclophosphamide (Cytoxan)]] and completed 12 hours after the last dose of [[Cyclophosphamide (Cytoxan)]] (total dose per cycle: 1800 mg/m<sup>2</sup>)
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycles 1, 3, 5, 7: 10 mcg/kg SC once per day, starting 24 hours after completion of chemotherapy, given until WBC greater than 3 x 10<sup>9</sup>/L or bone pain present
 
−
*ONE of the following antibiotics:
 
−
**[[:Category:Fluoroquinolone|Fluoroquinolone]]
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg dose/route not specified
 
−
*[[Fluconazole (Diflucan)]] dose/route not specified
 
−
*ONE of the following antivirals:
 
−
**[[Acyclovir (Zovirax)]] dose/route not specified
 
−
**[[Valacyclovir (Valtrex)]] dose/route not specified
 
−
'''Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is greater than 3 x 10<sup>9</sup>/L and platelet count greater than 50 x 10<sup>9</sup>/L'''
 
−
====Dose modifications, Part A====
 
−
*[[Vincristine (Oncovin)]] reduced to 1 mg for bilirubin greater than 2 mg/dL or NCI common toxicity criteria Grade 2+ peripheral neuropathy, omitted for bilirubin greater than 3 mg/dL or for ileus
 
−
*[[Doxorubicin (Adriamycin)]] reduced by 50% for bilirubin 2 to 3 mg/dL, by 75% for bilirubin 3 to 5 mg/dL (eliminated for bilirubin greater than 5 mg/dL or for gastric/small-bowel involvement with Course 1 to reduce duration of myelosuppression given risk of perforation)
 
−
====Targeted therapy, Part B====
 
−
*[[Rituximab (Rituxan)]] as follows:
 
−
**Cycles 2 & 4: 375 mg/m<sup>2</sup> IV over 2 to 6 hours once per day on days 2 & 8
 
−
====Chemotherapy, Part B====
 
−
*[[Methotrexate (MTX)]] as follows:
 
−
**Cycles 2, 4, 6, 8: 1000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
*[[Cytarabine (Ara-C)]] as follows:
 
−
**Cycles 2, 4, 6, 8: 3000 mg/m<sup>2</sup> IV over 2 hours every 12 hours on days 2 & 3 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
====Supportive therapy, Part B====
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycles 2, 4, 6, 8: 50 mg IV once 12 hours after [[Methotrexate (MTX)]] is complete, then 15 mg IV every 6 hours until serum methotrexate level less than 100 nmol/L
 
−
*[[Filgrastim (Neupogen)]] as follows:
 
−
**Cycles 2, 4, 6, 8: 10 mcg/kg SC once per day, starting 24 hours after completion of chemotherapy, given until WBC greater than 3 x 10<sup>9</sup>/L or bone pain present
 
−
*ONE of the following antibiotics:
 
−
**[[:Category:Fluoroquinolone|Fluoroquinolone]]
 
−
**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg dose/route not specified
 
−
*[[Fluconazole (Diflucan)]] dose/route not specified
 
−
*ONE of the following antivirals:
 
−
**[[Acyclovir (Zovirax)]] dose/route not specified
 
−
**[[Valacyclovir (Valtrex)]] dose/route not specified
 
−
'''Next cycle to start no sooner than 14 days or as soon as "unmaintained" WBC count is greater than 3 x 10<sup>9</sup>/L and platelet count greater than 50 x 10<sup>9</sup>/L'''
 
−
====Dose modifications, Part B====
 
−
*[[Cytarabine (Ara-C)]] reduced to 1000 mg/m<sup>2</sup> for patients greater than or equal to 60 years old, creatinine greater than or equal to 1.5 mg/dL or 0 hour MTX level greater than or equal to 20,000 nmol/L
 
−
*[[Methotrexate (MTX)]] reduced by 50% for creatinine clearance 10 to 50 mL/min (eliminated for less than 10 mL/min), by 25% to 75% for delayed excretion and/or nephrotoxicity with prior course (dependent on severity) or by 50% for pleural effusions/ascites with drainage of fluid as feasible.
 
−
====CNS therapy, prophylaxis====
 
−
*[[Methotrexate (MTX)]] by the following route-based criteria:
 
−
**LP: 12 mg IT once on day 2
 
−
**Ommaya reservoir: 6 mg IT once on day 2
 
−
*[[Cytarabine (Ara-C)]] 100 mg IT once on day 7
 
−
'''Given each cycle for a total of 16 intrathecal treatments.'''
 
−
''If CNS disease present, therapy augmented to twice-weekly alternating (MTX, ara-C) treatments until CSF cell count normalizes and cytology is negative, then continues for 4 more alternating weekly treatments; prophylaxis course then resumes.''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# Thomas DA, Faderl S, O'Brien S, Bueso-Ramos C, Cortes J, Garcia-Manero G, Giles FJ, Verstovsek S, Wierda WG, Pierce SA, Shan J, Brandt M, Hagemeister FB, Keating MJ, Cabanillas F, Kantarjian H. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006 Apr 1;106(7):1569-80. [https://doi.org/10.1002/cncr.21776 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16502413 PubMed]
+
<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
−
=Consolidation/Intensification therapy=
+
#'''CA184-041:''' Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [https://doi.org/10.1200/jco.2011.38.4032 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22547592 PubMed] NCT00527735
−
==BASIC {{#subobject:eb66c6|Regimen=1}}==
+
==Pembrolizumab monotherapy {{#subobject:0hg651|Regimen=1}}==
−
BASIC: '''<u>B</u>'''rief, '''<u>A</u>'''nthracycline-'''<u>S</u>'''paring, '''<u>I</u>'''ntensive '''<u>C</u>'''yclophosphamide
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:301df4|Variant=1}}===
+
===Regimen {{#subobject:d2e0eb|Variant=1}}===
−
{| class="wikitable" style="width: 40%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
−
!style="width: 25%"|Study
+
! style="width: 20%" |Study
−
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234101/ Kasamon et al. 2012 (J0409)]
+
|Awaiting publication (ZEAL-1L)
−
|style="background-color:#91cf61"|Non-randomized
+
|2020-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Niraparib_.26_Pembrolizumab_88|Niraparib & Pembrolizumab]]
 +
| style="background-color:#d3d3d3" |In progress
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#BASIC|BASIC]] induction
+
*[[Regimen_classes#Platinum-based_regimen|Platinum-based]] induction
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy, part 1====
+
====Immunotherapy====
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
−
====Chemotherapy, part 1====
+
'''21-day cycles'''
−
*[[Cyclophosphamide (Cytoxan)]] 50 mg/kg IV over 1 to 2 hours once per day on days 2 to 5
 
−
====Supportive therapy, part 1====
 
−
*[[Mesna (Mesnex)]] 40 mg/kg/day IV in divided doses on days 2 to 5
 
−
*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting on day 11 and continuing until post-nadir ANC greater than 1000/uL
 
−
'''One course, followed once post-nadir ANC greater than 1000/uL by:'''
 
−
====Targeted therapy, part 2====
 
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''4-week course'''
 
−
====CNS therapy, treatment, part 2====
 
−
*(only given if there was prior CNS involvement):
 
−
*[[Cytarabine (Ara-C)]] 100 mg IT once per week for 4 doses, then once every other week for 4 doses
 
−
*[[Hydrocortisone (Cortef)]] 50 mg IT is optional (no parameters given)
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- Presented in part at the 2009 American Society of Hematology annual meeting -->
+
#'''ZEAL-1L:''' NCT04475939
−
# '''J0409:''' Kasamon YL, Brodsky RA, Borowitz MJ, Ambinder RF, Crilley PA, Cho SY, Tsai HL, Smith BD, Gladstone DE, Carraway HE, Huff CA, Matsui WH, Bolaños-Meade J, Jones RJ, Swinnen LJ. Brief intensive therapy for older adults with newly diagnosed Burkitt or atypical Burkitt lymphoma/leukemia. Leuk Lymphoma. 2013 Mar;54(3):483-90. Epub 2012 Aug 17. [https://doi.org/10.3109/10428194.2012.715346 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234101/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22835045 PubMed]
+
==Pemetrexed monotherapy {{#subobject:ed7aa9|Regimen=1}}==
−
==Cytarabine & Methotrexate (CYM) {{#subobject:b24b28|Regimen=1}}==
+
===Example orders===
−
CYM: '''<u>CY</u>'''tarabine, '''<u>M</u>'''ethotrexate
+
*[[Example orders for Pemetrexed (Alimta) in non-small cell lung cancer]]
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:d51545|Variant=1}}===
+
===Regimen {{#subobject:2b465b|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="color:white; background-color:#404040"
−
!style="width: 33%"|Study
+
|<small>'''FDA-recommended dose'''</small>
−
!style="width: 33%"|Years of enrollment
+
|-
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(09)61497-5 Ciuleanu et al. 2009 (JMEN)]
 +
|2005-2007
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo_4|Placebo]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.4 vs 10.6 mo<br>(HR 0.79, 95% CI 0.65-0.95)
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1606774 Reck et al. 2016 (KEYNOTE-024)]
 +
|2014-2015
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(18)32409-7 Mok et al. 2019 (KEYNOTE-042)]
 +
|2014-2017
 +
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://doi.org/10.1056/NEJMoa1801005 Gandhi et al. 2018 (KEYNOTE-189)]
−
|1996-2001
+
|2016-2017
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#fdcdac">
+
<div class="toccolours" style="background-color:#cbd5e8">
−
====Eligibility criteria====
+
====Preceding treatment====
−
*Group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement)
+
*JMEN: [[Regimen_classes#Platinum-based_regimen|Platinum-based chemotherapy]] x 4
 +
*KEYNOTE-024: [[#Carboplatin_.26_Paclitaxel_.28CP.29_5|Carboplatin & Paclitaxel]] or [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]] or [[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]]
 +
*KEYNOTE-189 (control arm): [[#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]] x 4 or [[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] x 4
 +
*KEYNOTE-189 (experimental arm): [[#Pemetrexed_.26_Pembrolizumab|Pemetrexed & Pembrolizumab]] maintenance x 2 y
 +
*KEYNOTE-042: [[#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]] x 6
 
</div>
 
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
 +
====Supportive therapy====
 +
*[[Folic acid (Folate)]]
 +
*[[Cyanocobalamin (Vitamin B12)]]
 +
*[[Dexamethasone (Decadron)]]
 +
*"Investigators followed current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines for use of colony-stimulating factors and erythropoiesis-stimulating agents."
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''JMEN:''' Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Rodrigues Pereira J, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. Epub 2009 Sep 18. [https://doi.org/10.1016/S0140-6736(09)61497-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19767093 PubMed] NCT00102804
 +
#'''KEYNOTE-024:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. [https://doi.org/10.1056/NEJMoa1606774 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1606774/suppl_file/nejmoa1606774_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27718847 PubMed] NCT02142738
 +
##'''HRQoL analysis:''' Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. [https://doi.org/10.1016/S1470-2045(17)30690-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29129441 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. [https://doi.org/10.1200/JCO.18.00149 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30620668 PubMed]
 +
##'''Update:''' Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. [https://doi.org/10.1200/jco.21.00174 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280089/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33872070/ PubMed]
 +
#'''KEYNOTE-189:''' Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Epub 2018 Apr 16. [https://doi.org/10.1056/NEJMoa1801005 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1801005/suppl_file/nejmoa1801005_protocol.pdf link to protocol] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29658856 PubMed] NCT02578680
 +
<!-- # '''Abstract:''' Tony Mok, Yi-Long Wu, Patricia A, Watson, Jin Zhang, Reshma A. Rangwala, and Gilberto Lopes. Phase 3 KEYNOTE-042 trial of pembrolizumab (MK-3475) versus platinum doublet chemotherapy in treatment-naive patients (pts) with PD-L1–positive advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology 2015 33:15_suppl, TPS8105-TPS8105 [https://doi.org/10.1200/jco.2015.33.15_suppl.tps8105 link to abstract] -->
 +
#'''KEYNOTE-042:''' Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. [https://doi.org/10.1016/S0140-6736(18)32409-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30955977 PubMed] NCT02220894
 +
==Pemetrexed & Pembrolizumab {{#subobject:4f9073|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:0365c3|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1801005 Gandhi et al. 2018 (KEYNOTE-189)]
 +
|2016-2017
 +
|style="background-color:#1a9851"|Phase 3 (E-esc)
 +
|[[Complex_multipart_regimens#KEYNOTE-189|See link]]
 +
|style="background-color:#1a9850"|[[Complex_multipart_regimens#KEYNOTE-189|See link]]
 +
|-
 +
|}
 
<div class="toccolours" style="background-color:#cbd5e8">
 
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
−
*[[#COPADM|COPADM]]
+
*[[Non-small_cell_lung_cancer#Carboplatin.2C_Pemetrexed.2C_Pembrolizumab|Carboplatin, Pemetrexed, Pembrolizumab]] x 4 or [[Non-small_cell_lung_cancer#Cisplatin.2C_Pemetrexed.2C_Pembrolizumab|Cisplatin, Pemetrexed, Pembrolizumab]] x 4
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 200 mg IV over 30 minutes once on day 1, '''given first, at least 30 minutes prior to pemetrexed'''
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 2 (total dose per cycle: 500 mg/m<sup>2</sup>)
+
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given second'''
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours on days 2 to 4
+
*[[Folic acid (Folate)]] according to local guidelines
−
====CNS therapy, prophylaxis====
+
*[[Cyanocobalamin (Vitamin B12)]] according to local guidelines
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 2
+
*[[:Category:Steroids|Corticosteroids]] according to local guidelines
−
*[[Cytarabine (Ara-C)]] 30 mg IT once on day 6
+
'''21-day cycle for up to 2 years (35 cycles total, including induction)'''
−
*[[Hydrocortisone (Cortef)]] 15 mg IT once per day on days 2 & 6 (admixed with chemo)
 
−
'''2 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 10<sup>9</sup>/L'''
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#cbd5e7">
 
<div class="toccolours" style="background-color:#cbd5e7">
 
====Subsequent treatment====
 
====Subsequent treatment====
−
*[[#COPADM_2|COPADM]] maintenance
+
*[[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_2|Pemetrexed]] maintenance
 +
</div></div>
 +
===References===
 +
# '''KEYNOTE-189:''' Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Epub 2018 Apr 16. [https://doi.org/10.1056/NEJMoa1801005 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1801005/suppl_file/nejmoa1801005_protocol.pdf link to protocol] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29658856 PubMed] NCT02578680
 +
=Advanced or metastatic disease, second-line=
 +
==Cabozantinib monotherapy {{#subobject:47f237|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1276ee|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 +
|rowspan=2|2013-2014
 +
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 +
|1. [[#Cabozantinib_.26_Erlotinib|Cabozantinib & Erlotinib]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Cabozantinib (Cometriq)]] 60 mg PO once per day
 +
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
−
 
+
==Cabozantinib & Erlotinib {{#subobject:d9d1c0|Regimen=1}}==
−
==CYVE {{#subobject:8cd382|Regimen=1}}==
 
−
CYVE: '''<u>CY</u>'''tarabine, '''<u>VE</u>'''pesid (Etoposide)
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:ba1c35|Variant=1}}===
+
===Regimen {{#subobject:238161|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 33%"|Study
+
!style="width: 20%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 +
|rowspan=2|2013-2014
 +
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|1. [[#Cabozantinib_monotherapy|Cabozantinib]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Cabozantinib (Cometriq)]] 40 mg PO once per day
 +
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
 +
==Carboplatin & Pemetrexed {{#subobject:60fd1d|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Carboplatin (Paraplatin) and Pemetrexed (Alimta) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:95c37d|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.43.6758 Ardizzoni et al. 2012 (GOIRC 02-2006)]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|[[#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second'''
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
 +
====Supportive therapy====
 +
*(Ardizzoni et al. 2012 contained more details):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycle for 4 to 6 cycles'''
 +
</div></div>
 +
===References===
 +
<!-- Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, June 3-7, 2011; 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011; and 13th National Congress of Medical Oncology, Bologna, Italy, November 5-7, 2011. -->
 +
#'''GOIRC 02-2006:''' Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [https://doi.org/10.1200/jco.2012.43.6758 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23109689 PubMed] NCT00786331
 +
==Docetaxel monotherapy {{#subobject:ffa516|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Docetaxel (Taxotere) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 33.3 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:5b378|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(08)00307-3 Gebbia et al. 2008 (DISTAL-2)]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Capecitabine_.26_Docetaxel_.28TX.29|Capecitabine & Docetaxel]]<br> 2.[[#Docetaxel_.26_Gemcitabine_99|Docetaxel & Gemcitabine]]<br> 3. [[#Docetaxel_.26_Vinorelbine|Docetaxel & Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 33.3 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 35 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:5b296|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.02.3739 Schuette et al. 2005]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]; 75 mg/m<sup>2</sup>, every 3 wks
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70310-3 Garassino et al. 2013 (TAILOR<sub>NSCLC</sub>)]
 +
|2007-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|}
 +
''Note that there is another trial named TAILOR in colorectal cancer.''
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] as follows:
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
 +
**10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 50 mg/m<sup>2</sup> q2wk, limited duration {{#subobject:4cf20a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994826/ Pallis et al. 2010 (HORG CT/04.14)]
−
|1996-2001
+
|2004-2008
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Carboplatin_.26_Docetaxel_99|Carboplatin & Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen is for group C (CNS and/or bone marrow involvement). Note the unusual schedule of cytarabine; presumably the low-dose and high-dose portions are given at separate times in the 24 hour period but this detail is not further specified in the manuscript.''
+
<div class="toccolours" style="background-color:#fdcdac">
−
<div class="toccolours" style="background-color:#cbd5e8">
+
====Prior treatment criteria====
−
====Preceding treatment====
+
*Previous treatment with a platinum-free regimen
−
*[[#COPADM|COPADM]]
 
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cytarabine (Ara-C)]] by the following split schedule:
+
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 15
−
**50 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 5
+
'''28-day cycle for up to 6 cycles'''
−
**3000 mg/m<sup>2</sup> IV over 3 hours once per day on days 2 to 5
+
</div></div><br>
−
*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> IV once per day on days 2 to 5
+
<div class="toccolours" style="background-color:#eeeeee">
−
'''2 cycles; intervals were as short as possible, as soon as the ANC was greater than 1500/uL and platelet count was greater than 100 × 10<sup>9</sup>/L'''
+
===Regimen variant #4, 60 mg/m<sup>2</sup> q3wk, limited duration {{#subobject:b90b5e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ Herbst et al. 2010 (ZODIAC)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Vandetanib|Docetaxel & Vandetanib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose. While statistically inferior, the median PFS difference was only 0.8 months.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #5, 60 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:3afa13|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdn705 Takeda et al. 2009 (JCOG 0104)]
 +
|2002-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Gemcitabine_99|Docetaxel & Gemcitabine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2013.52.4694 Kawaguchi et al. 2014 (DELTA<sub>NSCLC</sub>)]
 +
|2009-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#d9ef8b" |Might have superior PFS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(14)60845-X Garon et al. 2014 (REVEL)]
 +
|2010-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Ramucirumab|Docetaxel & Ramucirumab]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 Gridelli et al. 2018 (AvaALL)]
 +
|2011-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|Investigator's choice of:<br>1. [[#Docetaxel_.26_Bevacizumab_99|Docetaxel & Bevacizumab]]<br>2. [[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]<br>3. [[#Pemetrexed_.26_Bevacizumab_99|Pemetrexed & Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose, the dose used for East Asian patients in REVEL, and the dose used in Japanese patients in EAST-LC. Note that there is another trial named DELTA in indolent lymphoma.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over at least 60 minutes once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #6, 75 mg/m<sup>2</sup> q3wk, limited duration {{#subobject:500ace|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ Herbst et al. 2010 (ZODIAC)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Vandetanib|Docetaxel & Vandetanib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
''Note: while statistically inferior, the median PFS difference in ZODIAC was only 0.8 months.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycle for up to 6 cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #7, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:b495b6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 17%"|Study
 +
!style="width: 15%"|Years of enrollment
 +
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 17%"|Comparator
 +
!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409790/ Gridelli et al. 2004 (DISTAL 01)]
 +
|2000-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]; 33.3 mg/m<sup>2</sup>, 6 out of 8 wks
 +
|
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of QoL
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.02.3739 Schuette et al. 2005]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]; 35 mg/m<sup>2</sup>, 3 out of 4 wks
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391114/ Paz-Ares et al. 2008 (STELLAR 2)]
 +
|2002-2004
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Paclitaxel_poliglumex_monotherapy_77|Paclitaxel poliglumex]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.2009.23.4146 Krzakowski et al. 2010]
 +
|2003-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Vinflunine_monotherapy_88|Vinflunine]]
 +
| style="background-color:#eeee01" |Non-inferior PFS
 +
|
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(12)00616-2 Sun et al. 2012 (JMID)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(11)70385-0 Ciuleanu et al. 2012 (TITAN)]
 +
|2006-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70310-3 Garassino et al. 2013 (TAILOR<sub>NSCLC</sub>)]
 +
|2007-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(14)60845-X Garon et al. 2014 (REVEL)]
 +
|2010-2013
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Ramucirumab|Docetaxel & Ramucirumab]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 Gridelli et al. 2018 (AvaALL)]
 +
|2011-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|Investigator's choice of:<br>1. [[#Docetaxel_.26_Bevacizumab_99|Docetaxel & Bevacizumab]]<br>2. [[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]<br>3. [[#Pemetrexed_.26_Bevacizumab_99|Pemetrexed & Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|[https://doi.org/10.1200/JCO.19.00816 Pillai et al. 2019 (GALAXY-2)]
 +
|2013-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Ganetespib_77|Docetaxel & Ganetespib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 +
====Supportive therapy====
 +
*Per JMEI: [[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
 +
*Per Chem et al. 2006: [[Dexamethasone (Decadron)]] as follows:
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
 +
**10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''DISTAL 01:''' Gridelli C, Gallo C, Di Maio M, Barletta E, Illiano A, Maione P, Salvagni S, Piantedosi FV, Palazzolo G, Caffo O, Ceribelli A, Falcone A, Mazzanti P, Brancaccio L, Capuano MA, Isa L, Barbera S, Perrone F. A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer: the DISTAL 01 study. Br J Cancer. 2004 Dec 13;91(12):1996-2004. [https://www.nature.com/articles/6602241 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2409790/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15558071 PubMed]
 +
#Schuette W, Nagel S, Blankenburg T, Lautenschlaeger C, Hans K, Schmidt EW, Dittrich I, Schweisfurth H, von Weikersthal LF, Raghavachar A, Reissig A, Serke M. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol. 2005 Nov 20;23(33):8389-95. [https://doi.org/10.1200/JCO.2005.02.3739 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16293869 PubMed]
 +
#'''STELLAR 2:''' Paz-Ares L, Ross H, O'Brien M, Riviere A, Gatzemeier U, Von Pawel J, Kaukel E, Freitag L, Digel W, Bischoff H, García-Campelo R, Iannotti N, Reiterer P, Bover I, Prendiville J, Eisenfeld AJ, Oldham FB, Bandstra B, Singer JW, Bonomi P. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer. Br J Cancer. 2008 May 20;98(10):1608-13. Epub 2008 May 13. [https://www.nature.com/articles/6604372 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2391114/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18475293 PubMed]
 +
#'''DISTAL-2:''' Gebbia V, Gridelli C, Verusio C, Frontini L, Aitini E, Daniele B, Gamucci T, Mancuso G, Di Maio M, Gallo C, Perrone F, Morabito A. Weekly docetaxel vs docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients: the DISTAL-2 randomized trial. Lung Cancer. 2009 Feb;63(2):251-8. Epub 2008 Jul 15. [https://www.lungcancerjournal.info/article/S0169-5002(08)00307-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18632181 PubMed] NCT00345059
 +
#'''JCOG 0104:''' Takeda K, Negoro S, Tamura T, Nishiwaki Y, Kudoh S, Yokota S, Matsui K, Semba H, Nakagawa K, Takada Y, Ando M, Shibata T, Saijo N. Phase III trial of docetaxel plus gemcitabine versus docetaxel in second-line treatment for non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG0104). Ann Oncol. 2009 May;20(5):835-41. Epub 2009 Jan 22. [https://doi.org/10.1093/annonc/mdn705 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19164456 PubMed]
 +
#Krzakowski M, Ramlau R, Jassem J, Szczesna A, Zatloukal P, Von Pawel J, Sun X, Bennouna J, Santoro A, Biesma B, Delgado FM, Salhi Y, Vaissiere N, Hansen O, Tan EH, Quoix E, Garrido P, Douillard JY. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol. 2010 May 1;28(13):2167-73. Epub 2010 Mar 29. [https://doi.org/10.1200/JCO.2009.23.4146 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20351334 PubMed]
 +
#'''ZODIAC:''' Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. [https://doi.org/10.1016/S1470-2045(10)70132-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20570559 PubMed] NCT00312377
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/163 Project Data Sphere]
 +
#'''HORG CT/04.14:''' Pallis AG, Agelaki S, Agelidou A, Varthalitis I, Syrigos K, Kentepozidis N, Pavlakou G, Kotsakis A, Kontopodis E, Georgoulias V. A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic non-small cell lung cancer. BMC Cancer. 2010 Nov 19;10:633. [https://doi.org/10.1186/1471-2407-10-633 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994826/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21092076 PubMed] NCT00430651
 +
#'''TITAN:''' Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. [https://doi.org/10.1016/S1470-2045(11)70385-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22277837 PubMed] NCT00556322
 +
#'''JMID:''' Sun Y, Wu YL, Zhou CC, Zhang L, Zhang L, Liu XY, Yu SY, Jiang GL, Li K, Qin SK, Ma SL, Han L, Quinlivan M, Orlando M, Zhang XQ. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer. 2013 Feb;79(2):143-50. Epub 2012 Nov 20. [https://www.lungcancerjournal.info/article/S0169-5002(12)00616-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23182660 PubMed] NCT00391274
 +
#'''TAILOR:''' Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. [https://doi.org/10.1016/S1470-2045(13)70310-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23883922 PubMed] NCT00637910
 +
#'''DELTA:''' Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. [https://doi.org/10.1200/JCO.2013.52.4694 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24841974 PubMed]
 +
#'''REVEL:''' Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. [https://doi.org/10.1016/S0140-6736(14)60845-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24933332 PubMed] NCT01168973
 +
#'''AvaALL:''' Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2698039 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30177994 PubMed] NCT01351415
 +
#'''GALAXY-2:''' Pillai RN, Fennell DA, Kovcin V, Ciuleanu TE, Ramlau R, Kowalski D, Schenker M, Yalcin I, Teofilovici F, Vukovic VM, Ramalingam SS. Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2). J Clin Oncol. 2020 Feb 20;38(6):613-622. Epub 2019 Dec 12. [https://doi.org/10.1200/JCO.19.00816 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31829907 PubMed] NCT01798485
 +
#'''DUBLIN-3:''' NCT02504489
 +
==Docetaxel & Ramucirumab {{#subobject:7b9570|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 60 mg/m<sup>2</sup> docetaxel {{#subobject:07d626|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(14)60845-X Garon et al. 2014 (REVEL)]
 +
|2010-2013
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.5 vs 9.1 mo<br>(HR 0.86, 95% CI 0.75-0.98)
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose and the dose recommended for East Asians. The FDA only provides recommendations for ramucirumab dosing.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Ramucirumab (Cyramza)]] 10 mg/kg IV once on day 1
 +
====Supportive therapy====
 +
*Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75 mg/m<sup>2</sup> docetaxel {{#subobject:b3ec19|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(14)60845-X Garon et al. 2014 (REVEL)]
 +
|2010-2013
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.5 vs 9.1 mo<br>(HR 0.86, 95% CI 0.75-0.98)
 +
|-
 +
|}
 +
''Note: The FDA only provides recommendations for ramucirumab dosing.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Ramucirumab (Cyramza)]] 10 mg/kg IV once on day 1
 +
====Supportive therapy====
 +
*Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''REVEL:''' Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. [https://doi.org/10.1016/S0140-6736(14)60845-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24933332 PubMed] NCT01168973
 +
==Docetaxel & Vandetanib {{#subobject:827eac|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 60 mg/m<sup>2</sup> docetaxel {{#subobject:c0b4c2|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ Herbst et al. 2010 (ZODIAC)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4 vs 3.2 mo<br>(HR 0.79, 97.58% CI 0.70-0.90)
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose of docetaxel. While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] as follows:
 +
**Cycles 1 up to 6: 60 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Vandetanib (Caprelsa)]] 100 mg PO once per day
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75 mg/m<sup>2</sup> docetaxel {{#subobject:10fe1c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ Herbst et al. 2010 (ZODIAC)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Docetaxel_monotherapy_2|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4 vs 3.2 mo<br>(HR 0.79, 97.58% CI 0.70-0.90)
 +
|-
 +
|}
 +
''While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.''
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Vandetanib (Caprelsa)]] 100 mg PO once per day
 +
'''21-day cycle for up to 6 cycles (see note)'''
 +
</div></div>
 +
===References===
 +
#'''ZODIAC:''' Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. [https://doi.org/10.1016/S1470-2045(10)70132-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225192/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20570559 PubMed] NCT00312377
 +
==Gefitinib monotherapy {{#subobject:ebfac2d|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1b01c8f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/full/10.1002/cncr.27630 Sun et al. 2012 (KCSG-LU08-01)]
 +
|2008-2010
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 9 vs 3 mo<br>(HR 0.54, 95% CI 0.37-0.79)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Gefitinib (Iressa)]] 250 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''KCSG-LU08-01:''' Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, Kim HK, Song HS, Kim YH, Kim BS, Hwang IG, Lee K, Jo SJ, Lee JW, Ahn JS, Park K, Ahn MJ; Korean Cancer Study Group. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012 Dec 15;118(24):6234-42. Epub 2012 Jun 6. [https://doi.org/full/10.1002/cncr.27630 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22674612 PubMed] NCT01066195
 +
==Gemcitabine monotherapy {{#subobject:b327a9|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:dac826|Variant=1}}===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
! style="width: 50%" |Study
 +
! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1999.17.7.2081 Crinò et al. 1999a]
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#Crinò L, Mosconi AM, Scagliotti G, Selvaggi G, Novello S, Rinaldi M, Della Giulia M, Gridelli C, Rossi A, Calandri C, De Marinis F, Noseda M, Tonato M. Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol. 1999 Jul;17(7):2081-5. [https://doi.org/10.1200/JCO.1999.17.7.2081 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10561261 PubMed]
 +
==Pemetrexed monotherapy {{#subobject:24fa23b|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Pemetrexed (Alimta) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4e0b1b|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdm592 Cullen et al. 2008 (JMGX)]
 +
|2004-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pemetrexed_monotherapy_3|Pemetrexed]]; high-dose
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.lungcancerjournal.info/article/S0169-5002(12)00616-2 Sun et al. 2012 (JMID)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(11)70385-0 Ciuleanu et al. 2012 (TITAN)]
 +
|2006-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2010.29.5717 de Boer et al. 2011 (ZEAL)]
 +
|2007-2008
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Pemetrexed_.26_Vandetanib|Pemetrexed & Vandetanib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.43.6758 Ardizzoni et al. 2012 (GOIRC 02-2006)]
 +
|2007-2009
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Carboplatin_.26_Pemetrexed_4|Carboplatin & Pemetrexed]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|[https://doi.org/full/10.1002/cncr.27630 Sun et al. 2012 (KCSG-LU08-01)]
 +
|2008-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gefitinib_monotherapy_3|Gefitinib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 Gridelli et al. 2018 (AvaALL)]
 +
|2011-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|Investigator's choice of:<br>1. [[#Docetaxel_.26_Bevacizumab_99|Docetaxel & Bevacizumab]]<br>2. [[#Erlotinib_.26_Bevacizumab_99|Erlotinib & Bevacizumab]]<br>3. [[#Pemetrexed_.26_Bevacizumab_99|Pemetrexed & Bevacizumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
 +
====Supportive therapy====
 +
*(per Ardizzoni et al. 2012):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycles'''
 +
''GOIRC 02-2006 treated patients for up to 4 cycles or until progressive disease, unacceptable toxicity, or patient refusal.''
 +
</div></div>
 +
===References===
 +
#'''JMGX:''' Cullen MH, Zatloukal P, Sörenson S, Novello S, Fischer JR, Joy AA, Zereu M, Peterson P, Visseren-Grul CM, Iscoe N. A randomized phase III trial comparing standard and high-dose pemetrexed as second-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2008 May;19(5):939-45. Epub 2008 Feb 17. [https://doi.org/10.1093/annonc/mdm592 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18283036 PubMed] NCT00078260
 +
<!-- Presented as a poster discussion at the 45th Annual Meeting of the American Society of Clinical Oncology, May 29-June 2, 2009, Orlando, FL, and as an oral presentation at the 13th World Congress on Lung Cancer, July 31-August 4, 2009, San Francisco, CA, and at the European Cancer Organisation 15/34th European Society for Medical Oncology Congress, September 20-24, 2009, Berlin, Germany. -->
 +
#'''ZEAL:''' de Boer RH, Arrieta Ó, Yang CH, Gottfried M, Chan V, Raats J, de Marinis F, Abratt RP, Wolf J, Blackhall FH, Langmuir P, Milenkova T, Read J, Vansteenkiste JF. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2011 Mar 10;29(8):1067-74. Epub 2011 Jan 31. [https://doi.org/10.1200/JCO.2010.29.5717 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21282537 PubMed] NCT00418886
 +
#'''TITAN:''' Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. [https://doi.org/10.1016/S1470-2045(11)70385-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22277837 PubMed] NCT00556322
 +
#'''KCSG-LU08-01:''' Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, Kim HK, Song HS, Kim YH, Kim BS, Hwang IG, Lee K, Jo SJ, Lee JW, Ahn JS, Park K, Ahn MJ; Korean Cancer Study Group. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012 Dec 15;118(24):6234-42. Epub 2012 Jun 6. [https://doi.org/full/10.1002/cncr.27630 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22674612 PubMed] NCT01066195
 +
<!-- Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, June 3-7, 2011; 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011; and 13th National Congress of Medical Oncology, Bologna, Italy, November 5-7, 2011. -->
 +
#'''GOIRC 02-2006:''' Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [https://doi.org/10.1200/jco.2012.43.6758 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23109689 PubMed] NCT00786331
 +
#'''JMID:''' Sun Y, Wu YL, Zhou CC, Zhang L, Zhang L, Liu XY, Yu SY, Jiang GL, Li K, Qin SK, Ma SL, Han L, Quinlivan M, Orlando M, Zhang XQ. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer. 2013 Feb;79(2):143-50. Epub 2012 Nov 20. [https://www.lungcancerjournal.info/article/S0169-5002(12)00616-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23182660 PubMed] NCT00391274
 +
#'''AvaALL:''' Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2698039 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440713 link to PMC article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30177994 PubMed] NCT01351415
 +
=Advanced or metastatic disease, third-line=
 +
==Cabozantinib monotherapy {{#subobject:47f237|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:1276ee|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 +
|rowspan=2|2013-2014
 +
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 +
|1. [[#Cabozantinib_.26_Erlotinib|Cabozantinib & Erlotinib]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Cabozantinib (Cometriq)]] 60 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
 +
==Cabozantinib & Erlotinib {{#subobject:d9d1c0|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:238161|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(16)30561-7 Neal et al. 2016 (ECOG-ACRIN 1512)]
 +
|rowspan=2|2013-2014
 +
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 +
|1. [[#Cabozantinib_monotherapy|Cabozantinib]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|2. [[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Cabozantinib (Cometriq)]] 40 mg PO once per day
 +
*[[Erlotinib (Tarceva)]] 150 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''ECOG-ACRIN 1512:''' Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. [https://doi.org/10.1016/S1470-2045(16)30561-7 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154681/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27825638 PubMed] NCT01708954
 +
==Docetaxel monotherapy {{#subobject:ff8fa6|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Docetaxel (Taxotere) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 60 mg/m<sup>2</sup> {{#subobject:3a685a|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2013.52.4694 Kawaguchi et al. 2014 (DELTA<sub>NSCLC</sub>)]
 +
|2009-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#d9ef8b" |Might have superior PFS
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose. Note that there is another trial named DELTA in indolent lymphoma.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over at least 60 minutes once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 75 mg/m<sup>2</sup> {{#subobject:3h15ba|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|Awaiting publication (CANOPY-2)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Canakinumab_77|Docetaxel & Canakinumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|Awaiting publication (LEAP-008)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Lenvatinib_.26_Pembrolizumab_66|Lenvatinib & Pembrolizumab]]<br>2. [[#Lenvatinib_monotherapy_66|Lenvatinib]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|Awaiting publication (SAPPHIRE)
 +
|2019-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Sitravantinib_.26_Nivolumab_77|Sitravantinib & Nivolumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|Awaiting publication (CONTACT-01)
 +
|2020-ongoing
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Cabozantinib_.26_Atezolizumab_66|Cabozantinib & Atezolizumab]]
 +
| style="background-color:#d3d3d3" |Awaiting results
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''DELTA:''' Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. [https://doi.org/10.1200/JCO.2013.52.4694 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24841974 PubMed]
 +
#'''CANOPY-2:''' NCT03626545
 +
#'''CONTACT-01:''' NCT04471428
 +
#'''LEAP-008:''' NCT03976375
 +
#'''SAPPHIRE:''' NCT03906071
 +
=Advanced or metastatic disease, subsequent lines of therapy=
 +
''Note: this section includes regimens that were tested in second-line and beyond; those tested specifically in the [[#Advanced_or_metastatic_disease.2C_second-line|second-line]] or [[#Advanced_or_metastatic_disease.2C_third-line|third-line]] are to be found above.''
 +
==Afatinib monotherapy {{#subobject:1bf6db|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 30 mg/day {{#subobject:f69d3b|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
''Note: This is the FDA-recommended dose for patients with "severe renal impairment".''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Afatinib (Gilotrif)]] 30 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 50 mg/day {{#subobject:f109f9|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(12)70087-6 Miller et al. 2012 (LUX-Lung 1)]
 +
|2008-2009
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo_5|Placebo]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|[https://doi.org/10.1200/jco.2012.45.0981 Katakami et al. 2013 (LUX-Lung 4)]
 +
|2009-2011
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#6e016b; color:white " |ORR: 8% (95% CI: 3-18)
 +
|-
 +
|}
 +
''In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants, who had progressed while receiving erlotinib and/or gefitinib and had received one or two previous lines of chemotherapy, including at least one platinum-based regimen.''
 +
====Targeted therapy====
 +
*[[Afatinib (Gilotrif)]] 50 mg PO once per day, given 1 hour before eating food
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''LUX-Lung 1:''' Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. [https://doi.org/10.1016/S1470-2045(12)70087-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22452896 PubMed] NCT00656136
 +
##'''HRQoL analysis:''' Hirsh V, Cadranel J, Cong XJ, Fairclough D, Finnern HW, Lorence RM, Miller VA, Palmer M, Yang JC. Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1). J Thorac Oncol. 2013 Feb;8(2):229-37. [https://www.jto.org/article/S1556-0864(15)32746-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23328549 PubMed]
 +
#'''LUX-Lung 4:''' Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.45.0981 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23816963 PubMed] NCT00711594
 +
==Afatinib & Paclitaxel {{#subobject:3d0a87|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:0cb697|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769992/ Schuler et al. 2015 (LUX-Lung 5)]
 +
|2010-2011
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|Single-agent chemotherapy
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Afatinib (Gilotrif)]] 40 mg PO once per day
 +
====Chemotherapy====
 +
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''LUX-Lung 5:''' Schuler M, Yang JC, Park K, Kim JH, Bennouna J, Chen YM, Chouaid C, De Marinis F, Feng JF, Grossi F, Kim DW, Liu X, Lu S, Strausz J, Vinnyk Y, Wiewrodt R, Zhou C, Wang B, Chand VK, Planchard D; LUX-Lung 5 Investigators. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol. 2016 Mar;27(3):417-23. Epub 2015 Dec 8. [https://doi.org/10.1093/annonc/mdv597 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769992/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26646759 PubMed] NCT01085136
 +
==Amrubicin monotherapy {{#subobject:d1a9ba|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f264a4|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdw621 Yoshioka et al. 2017 (D0702035)]
 +
|2010-2012
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Amrubicin (Calsed)]] 35 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''D0702035:''' Yoshioka H, Katakami N, Okamoto H, Iwamoto Y, Seto T, Takahashi T, Sunaga N, Kudoh S, Chikamori K, Harada M, Tanaka H, Saito H, Saka H, Takeda K, Nogami N, Masuda N, Harada T, Kitagawa H, Horio H, Yamanaka T, Fukuoka M, Yamamoto N, Nakagawa K. A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer. Ann Oncol. 2017 Feb 1;28(2):285-291. [https://doi.org/10.1093/annonc/mdw621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28426104 PubMed] NCT01207011
 +
==Atezolizumab monotherapy {{#subobject:412fc4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:9f357f|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(16)00587-0 Fehrenbacher et al. 2016 (POPLAR)]
 +
|2013-2014
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ooc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 12.6 vs 9.7 mo<br>(HR 0.73, 95% CI 0.53-0.99)
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(16)32517-X Rittmeyer et al. 2016 (OAK)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 13.8 vs 9.6 mo<br>(HR 0.75, 95% CI 0.64-0.89)
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy is based on the 2018 update for the primary efficacy group.''
 +
<div class="toccolours" style="background-color:#fdcdac">
 +
====Prior treatment criteria====
 +
*OAK: 1 or more [[Regimen_classes#Platinum-based_regimen|platinum-based combination therapies]]
 
</div>
 
</div>
−
<div class="toccolours" style="background-color:#cbd5e7">
+
<div class="toccolours" style="background-color:#b3e2cd">
−
====Subsequent treatment====
+
====Immunotherapy====
−
*[[#COPAD.2FCYVE|COPAD alternating with CYVE]] maintenance
+
*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''POPLAR:''' Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [https://doi.org/10.1016/S0140-6736(16)00587-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26970723 PubMed] NCT01903993
−
=Maintenance therapy=
+
#'''OAK:''' Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. Epub 2016 Dec 13. [https://doi.org/10.1016/S0140-6736(16)32517-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/27979383 PubMed] NCT02008227
−
==COPAD/CYVE {{#subobject:8337e0|Regimen=1}}==
+
##'''Update:''' Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, Han JY, Gadgeel SM, Hida T, Cortinovis DL, Cobo M, Kowalski DM, De Marinis F, Gandhi M, Danner B, Matheny C, Kowanetz M, He P, Felizzi F, Patel H, Sandler A, Ballinger M, Barlesi F. Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Aug;13(8):1156-1170. Epub 2018 May 17. Erratum in: J Thorac Oncol. 2018 Nov;13(11):1800. [https://www.jto.org/article/S1556-0864(18)30611-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29777823 PubMed]
−
COPAD/CYVE: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>AD</u>'''riamycin (Doxorubicin) alternating with '''<u>CY</u>'''tarabine, '''<u>VE</u>'''pesid (Etoposide)
+
##'''Update:''' von Pawel J, Bordoni R, Satouchi M, Fehrenbacher L, Cobo M, Han JY, Hida T, Moro-Sibilot D, Conkling P, Gandara DR, Rittmeyer A, Gandhi M, Yu W, Matheny C, Patel H, Sandler A, Ballinger M, Kowanetz M, Park K. Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. Eur J Cancer. 2019 Jan;107:124-132. Epub 2018 Dec 17. [https://www.ejcancer.com/article/S0959-8049(18)31518-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30562710 PubMed]
 +
==Docetaxel monotherapy {{#subobject:fd1716|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Docetaxel (Taxotere) in non-small cell lung cancer]]
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Protocol {{#subobject:16435a|Variant=1}}===
+
===Regimen variant #1, 35 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:5b296|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 33%"|Study
+
!style="width: 20%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[http://journal.chestnet.org/article/S0012-3692(15)38821-8 Chen et al. 2006]
 +
| rowspan="2" |2002-2004
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel]]; 40 mg/m<sup>2</sup>, 2 out of 3 wks
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoint
 +
|-
 +
|2. [[#Docetaxel_monotherapy_4|Docetaxel]]; 75 mg/m<sup>2</sup>, every 3 wks
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoint
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]] as follows:
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
 +
**10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
 +
**8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 60 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:3a67f3|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2007.15.0185 Maruyama et al. 2008 (V-15-32)]
 +
|2003-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gefitinib_monotherapy_99|Gefitinib]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2013.52.4694 Kawaguchi et al. 2014 (DELTA<sub>NSCLC</sub>)]
 +
|2009-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#d9ef8b" |Might have superior PFS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdw621 Yoshioka et al. 2017 (D0702035)]
 +
|2010-2012
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Amrubicin_monotherapy|Amrubicin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834128/ Nokihara et al. 2017 (EAST-LC)]
 +
|2010-2014
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#S-1_monotherapy|S-1]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|[https://doi.org/10.1016/j.jtho.2021.03.027 Yoneshima et al. 2021 (J-AXEL)]
 +
|2015-2018
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
''Note: This is the PMDA-approved dose, the dose used for East Asian patients in REVEL, and the dose used in Japanese patients in EAST-LC.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over at least 60 minutes once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #3, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:b495b6|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.10.2095 Shepherd et al. 2000 (TAX 317)]
 +
|1994-1998
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 +
|[[Non-small_cell_lung_cancer_-_historical#Best_supportive_care_2|Best supportive care]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/JCO.2000.18.12.2354 Fossella et al. 2000 (TAX 320)]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel]]; 100 mg/m<sup>2</sup>
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Ifosfamide_monotherapy_88|Ifosfamide]]<br> 3. [[#Vinorelbine_monotherapy_2|Vinorelbine]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://doi.org/10.1093/annonc/mdj115 Camps et al. 2005]
 +
|2000-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]; 36 mg/m<sup>2</sup>, 6 out of 8 wks
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|[https://doi.org/10.1200/jco.2004.08.163 Hanna et al. 2004 (JMEI)]
 +
|2001-2002
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pemetrexed_monotherapy_3|Pemetrexed]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2005.03.6491 Ramlau et al. 2006 (GSK 104864-A/387)]
 +
|2001-2003
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Topotecan_monotherapy_99|Topotecan]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
| rowspan="2" |[http://journal.chestnet.org/article/S0012-3692(15)38821-8 Chen et al. 2006]
 +
| rowspan="2" |2002-2004
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel]]; 35 mg/m<sup>2</sup>, 3 out of 4 wks
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoint
 +
|-
 +
|2. [[#Docetaxel_monotherapy_4|Docetaxel]]; 40 mg/m<sup>2</sup>, 2 out of 3 wks
 +
| style="background-color:#ffffbf" |Did not meet efficacy endpoint
 +
|-
 +
|[https://doi.org/10.1200/JCO.2008.17.1405 Fidias et al. 2008]
 +
|2002-2005
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_monotherapy_88|Docetaxel]] consolidation
 +
| style="background-color:#fee08b" |Might have inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(08)61758-4 Kim et al. 2008 (INTEREST)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gefitinib_monotherapy_3|Gefitinib]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior OS
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/16/4/1307.long Lee et al. 2010 (ISTANA)]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Gefitinib_monotherapy_3|Gefitinib]]
 +
| style="background-color:#fc8d59" |Seems to have inferior PFS
 +
|-
 +
|[https://doi.org/10.1200/JCO.2012.42.6932 Ramlau et al. 2012 (EFC10261)]
 +
|2007-2010 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Ziv-alifbercept|Docetaxel & Ziv-aflibercept]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.4 vs 10.1 mo<br>(HR 0.99, 95% CI 0.85-1.15)
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70586-2 Reck et al. 2014 (LUME-Lung 1)]
 +
|2008-2011
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Docetaxel_.26_Nintedanib|Docetaxel & Nintedanib]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834128/ Nokihara et al. 2017 (EAST-LC)]
 +
|2010-2014
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#S-1_monotherapy|S-1]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ Katakami et al. 2017 (E7389-G000-302)]
 +
|2011-2014 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Eribulin_monotherapy_99|Eribulin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 9.5 vs 9.5 mo<br>(HR 0.86, 95% CI 0.71-1.05)
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(16)00587-0 Fehrenbacher et al. 2016 (POPLAR)]
 +
|2013-2014
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Atezolizumab_monotherapy_3|Atezolizumab]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(15)01281-7 Herbst et al. 2015 (KEYNOTE-010)]
 +
|2013-2015
 +
| style="background-color:#1a9851" |Phase 2/3 (C)
 +
|1. [[#Pembrolizumab_monotherapy_4|Pembrolizumab]]; 2 mg/kg<br>2. [[#Pembrolizumab_monotherapy_4|Pembrolizumab]]; 10 mg/kg
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(16)32517-X Rittmeyer et al. 2016 (OAK)]
 +
|2014-2015
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Atezolizumab_monotherapy_3|Atezolizumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1016/j.jtho.2019.01.006 Wu et al. 2019 (CheckMate 078)]
 +
|2015-2016
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Nivolumab_monotherapy_2|Nivolumab]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(18)30673-9 Barlesi et al. 2018 (JAVELIN Lung 200)]
 +
|2015-2017
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Avelumab_monotherapy_99|Avelumab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|Awaiting publication (KN046-302)
−
|1996-2001
+
|2021-2024
−
|style="background-color:#ffffbe"|Phase 2, <20 pts in this subgroup
+
| style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Lenvatinib_monotherapy_66|Lenvatinib]]<br>2. [[#Lenvatinib_.26_KN046_77|Lenvatinib & KN046]]
 +
| style="background-color:#d3d3d3" |TBD
 
|-
 
|-
 
|}
 
|}
−
''Note: This protocol is for group C (CNS and/or bone marrow involvement). Note that the days of administration for the CYVE cycles are counted from the start of the respective COPAD cycles.''
+
<div class="toccolours" style="background-color:#fdcdac">
−
<div class="toccolours" style="background-color:#cbd5e8">
+
====Prior treatment criteria====
−
====Preceding treatment====
+
*OAK: 1 or more [[Regimen_classes#Platinum-based_regimen|platinum-based combination therapies]]
−
*[[#CYVE|CYVE]] consolidation
+
*CheckMate 078 & JAVELIN Lung 200: Failure of a [[Regimen_classes#Platinum_doublet|platinum doublet]]
 +
*KN046-302: Progression after first- or second-line PD-1 or PD-L1 inhibitor and [[Regimen_classes#Platinum_doublet|platinum-containing dual-agent chemotherapy]]
 
</div>
 
</div>
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy, COPAD cycles====
+
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+
====Supportive therapy====
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
+
*Per JMEI: [[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
−
====Glucocorticoid therapy====
+
*Per Chem et al. 2006: [[Dexamethasone (Decadron)]] as follows:
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5
+
**8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
−
====CNS therapy, treatment====
+
**10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
−
''Note: this is only given with the first cycle of maintenance; patients with positive CNS at diagnosis were to also undergo 24 Gy of cranial irradiation.''
+
**8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 2
+
'''21-day cycles'''
−
*[[Cytarabine (Ara-C)]] 40 mg IT once on day 2
+
</div></div><br>
−
*[[Hydrocortisone (Cortef)]] 15 mg IT once on day 2 (admixed with MTX & Ara-C)
+
<div class="toccolours" style="background-color:#eeeeee">
−
====Chemotherapy, CYVE cycles====
+
===Regimen variant #4, 100 mg/m<sup>2</sup> q3wk {{#subobject:465aa0|Variant=1}}===
−
*[[Cytarabine (Ara-C)]] 50 mg/m<sup>2</sup> SC twice per day on days 28 to 32
+
{| class="wikitable" style="width: 40%; text-align:center;"
−
*[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV once per day on days 28 to 30
+
! style="width: 25%" |Study
−
'''4 alternating cycles (COPAD, then CYVE, then COPAD, then CYVE)'''
+
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.1995.13.3.645 Fossella et al. 1995]
 +
| style="background-color:#91cf61" |Phase 2
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#Fossella FV, Lee JS, Shin DM, Calayag M, Huber M, Perez-Soler R, Murphy WK, Lippman S, Benner S, Glisson B, Chasen M, Hong WK, Raber M. Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. J Clin Oncol. 1995 Mar;13(3):645-51. [https://doi.org/10.1200/JCO.1995.13.3.645 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7884425 PubMed]
 +
#'''TAX 317:''' Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103. [https://doi.org/10.1200/JCO.2000.18.10.2095 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10811675 PubMed]
 +
#'''TAX 320:''' Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L; TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209. [https://doi.org/10.1200/JCO.2000.18.12.2354 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10856094 PubMed]
 +
#'''JMEI:''' Hanna N, Shepherd FA, Fossella FV, Rodrigues Pereira J, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar M, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [https://doi.org/10.1200/jco.2004.08.163 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15117980 PubMed]
 +
#Camps C, Massuti B, Jiménez A, Maestu I, Gómez RG, Isla D, González JL, Almenar D, Blasco A, Rosell R, Carrato A, Viñolas N, Batista N, Girón CG, Galán A, López M, Blanco R, Provencio M, Diz P, Felip E; Spanish Lung Cancer Group. Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial. Ann Oncol. 2006 Mar;17(3):467-72. Epub 2005 Dec 21. [https://doi.org/10.1093/annonc/mdj115 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16371411 PubMed]
 +
#Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest. 2006 Apr;129(4):1031-8. [http://journal.chestnet.org/article/S0012-3692(15)38821-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16608954 PubMed]
 +
#'''GSK 104864-A/387:''' Ramlau R, Gervais R, Krzakowski M, von Pawel J, Kaukel E, Abratt RP, Dharan B, Grotzinger KM, Ross G, Dane G, Shepherd FA. Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. J Clin Oncol. 2006 Jun 20;24(18):2800-7. Epub 2006 May 8. [https://doi.org/10.1200/JCO.2005.03.6491 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16682727 PubMed] NCT00049998
 +
#'''V-15-32:''' Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Inoue A, Tomii K, Harada M, Masuda N, Jiang H, Itoh Y, Ichinose Y, Saijo N, Fukuoka M. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008 Sep 10;26(26):4244-52. [https://doi.org/10.1200/JCO.2007.15.0185 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18779611 PubMed] NCT00252707
 +
##'''HRQoL analysis:''' Sekine I, Ichinose Y, Nishiwaki Y, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Itoh Y, Tamura T, Saijo N, Fukuoka M. Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel. Ann Oncol. 2009 Sep;20(9):1483-8. Epub 2009 Mar 12. [https://doi.org/10.1093/annonc/mdp031 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19282468 PubMed]
 +
#'''INTEREST:''' Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [https://doi.org/10.1016/S0140-6736(08)61758-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19027483 PubMed] NCT00076388
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/151 Project Data Sphere]
 +
#Fidias PM, Dakhil SR, Lyss AP, Loesch DM, Waterhouse DM, Bromund JL, Chen R, Hristova-Kazmierski M, Treat J, Obasaju CK, Marciniak M, Gill J, Schiller JH. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Feb 1;27(4):591-8. Epub 2008 Dec 15. [https://doi.org/10.1200/JCO.2008.17.1405 link to original article]'''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19075278 PubMed]
 +
#'''ISTANA:''' Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW. Randomized phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010 Feb 15;16(4):1307-14. Epub 2010 Feb 9. [http://clincancerres.aacrjournals.org/content/16/4/1307.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20145166 PubMed] NCT00478049
 +
<!-- Presented in part at the 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
 +
#'''EFC10261:''' Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, Baldotto C, Bennouna J, Shepherd FA, Le-Guennec S, Rey A, Miller V, Thatcher N, Scagliotti G. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10;30(29):3640-7. Epub 2012 Sep 10. [https://doi.org/10.1200/JCO.2012.42.6932 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22965962 PubMed] NCT00532155
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/133 Project Data Sphere]
 +
#'''LUME-Lung 1:''' Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. [https://doi.org/10.1016/S1470-2045(13)70586-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24411639 PubMed] NCT00805194
 +
#'''KEYNOTE-010:''' Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [https://doi.org/10.1016/S0140-6736(15)01281-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26712084 PubMed] NCT01905657
 +
##'''Update:''' Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020 May 10;38(14):1580-1590. Epub 2020 Feb 20. [https://doi.org/10.1200/jco.19.02446 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32078391/ PubMed]
 +
#'''POPLAR:''' Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [https://doi.org/10.1016/S0140-6736(16)00587-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26970723 PubMed] NCT01903993
 +
#'''OAK:''' Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. Epub 2016 Dec 13. [https://doi.org/10.1016/S0140-6736(16)32517-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27979383 PubMed] NCT02008227
 +
##'''Update:''' Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, Han JY, Gadgeel SM, Hida T, Cortinovis DL, Cobo M, Kowalski DM, De Marinis F, Gandhi M, Danner B, Matheny C, Kowanetz M, He P, Felizzi F, Patel H, Sandler A, Ballinger M, Barlesi F. Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Aug;13(8):1156-1170. Epub 2018 May 17. Erratum in: J Thorac Oncol. 2018 Nov;13(11):1800. [https://www.jto.org/article/S1556-0864(18)30611-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29777823 PubMed]
 +
##'''Update:''' von Pawel J, Bordoni R, Satouchi M, Fehrenbacher L, Cobo M, Han JY, Hida T, Moro-Sibilot D, Conkling P, Gandara DR, Rittmeyer A, Gandhi M, Yu W, Matheny C, Patel H, Sandler A, Ballinger M, Kowanetz M, Park K. Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. Eur J Cancer. 2019 Jan;107:124-132. Epub 2018 Dec 17. [https://www.ejcancer.com/article/S0959-8049(18)31518-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30562710 PubMed]
 +
#'''D0702035:''' Yoshioka H, Katakami N, Okamoto H, Iwamoto Y, Seto T, Takahashi T, Sunaga N, Kudoh S, Chikamori K, Harada M, Tanaka H, Saito H, Saka H, Takeda K, Nogami N, Masuda N, Harada T, Kitagawa H, Horio H, Yamanaka T, Fukuoka M, Yamamoto N, Nakagawa K. A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer. Ann Oncol. 2017 Feb 1;28(2):285-291. [https://doi.org/10.1093/annonc/mdw621 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28426104 PubMed] NCT01207011
 +
#'''E7389-G000-302:''' Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. [https://doi.org/10.1093/annonc/mdx284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911085 PubMed] NCT01454934
 +
#'''EAST-LC:''' Nokihara H, Lu S, Mok TSK, Nakagawa K, Yamamoto N, Shi YK, Zhang L, Soo RA, Yang JC, Sugawara S, Nishio M, Takahashi T, Goto K, Chang J, Maemondo M, Ichinose Y, Cheng Y, Lim WT, Morita S, Tamura T. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol. 2017 Nov 1;28(11):2698-2706. [https://doi.org/10.1093/annonc/mdx419 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834128/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29045553 PubMed] JapicCTI-101155
 +
#'''JAVELIN Lung 200:''' Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F, Özgüroğlu M, Szczesna A, Polychronis A, Uslu R, Krzakowski M, Lee JS, Calabrò L, Arén Frontera O, Ellers-Lenz B, Bajars M, Ruisi M, Park K. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1468-79. Epub 2018 Sep 21. [https://doi.org/10.1016/S1470-2045(18)30673-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30262187 PubMed] NCT02395172
 +
##'''Update:''' Park K, Özgüroğlu M, Vansteenkiste J, Spigel D, Yang JCH, Ishii H, Garassino M, de Marinis F, Szczesna A, Polychronis A, Uslu R, Krzakowski M, Lee JS, Calabrò L, Arén Frontera O, Xiong H, Bajars M, Ruisi M, Barlesi F. Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial. J Thorac Oncol. 2021 Aug;16(8):1369-1378. Epub 2021 Apr 9. [https://doi.org/10.1016/j.jtho.2021.03.009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33845211/ PubMed]
 +
#'''CheckMate 078:''' Wu YL, Lu S, Cheng Y, Zhou C, Wang J, Mok T, Zhang L, Tu HY, Wu L, Feng J, Zhang Y, Luft AV, Zhou J, Ma Z, Lu Y, Hu C, Shi Y, Baudelet C, Cai J, Chang J. Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial. J Thorac Oncol. 2019 May;14(5):867-875. Epub 2019 Jan 17. [https://doi.org/10.1016/j.jtho.2019.01.006 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30659987 PubMed] NCT02613507
 +
##'''Update:''' Lu S, Wang J, Cheng Y, Mok T, Chang J, Zhang L, Feng J, Tu HY, Wu L, Zhang Y, Luft A, Zhou JY, Ma Z, Lu Y, Hu C, Shi Y, Ying K, Zhong H, Poddubskaya E, Soo RA, Chia YH, Li A, Li A, Wu YL. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078). Lung Cancer. 2021 Feb;152:7-14. Epub 2020 Nov 24. [https://doi.org/10.1016/j.lungcan.2020.11.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33321441/ PubMed]
 +
#'''J-AXEL:''' Yoneshima Y, Morita S, Ando M, Nakamura A, Iwasawa S, Yoshioka H, Goto Y, Takeshita M, Harada T, Hirano K, Oguri T, Kondo M, Miura S, Hosomi Y, Kato T, Kubo T, Kishimoto J, Yamamoto N, Nakanishi Y, Okamoto I. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol. 2021 Sep;16(9):1523-1532. Epub 2021 Apr 27. [https://doi.org/10.1016/j.jtho.2021.03.027 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33915251/ PubMed]
 +
#'''KN046-302:''' NCT05001724
 +
==Docetaxel & Nintedanib {{#subobject:f8yg16|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:5b63mi|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70586-2 Reck et al. 2014 (LUME-Lung 1)]
 +
|2008-2011
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 +
====Targeted therapy====
 +
*[[Nintedanib (Vargatef)]] 200 mg PO twice per day on days 2 to 21
 +
'''21-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#'''LUME-Lung 1:''' Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. [https://doi.org/10.1016/S1470-2045(13)70586-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24411639 PubMed] NCT00805194
−
==COPADM {{#subobject:ffa661|Regimen=1}}==
+
==Gefitinib monotherapy {{#subobject:ebbf2d|Regimen=1}}==
−
COPADM: '''<u>C</u>'''yclophosphamide, '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>AD</u>'''riamycin (Doxorubicin), '''<u>M</u>'''ethotrexate
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:79dd6f|Variant=1}}===
+
===Regimen {{#subobject:1b028f|Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable sortable" style="width: 100%; text-align:center;"
−
!style="width: 33%"|Study
+
!style="width: 20%"|Study
−
!style="width: 33%"|Years of enrollment
+
!style="width: 20%"|Years of enrollment
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[http://jama.jamanetwork.com/article.aspx?articleid=197532 Kris et al. 2003 (IDEAL2)]
 +
|2000-2001
 +
| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-de-esc)
 +
|[[#Gefitinib_monotherapy_3|Gefitinib]]; 500 mg/day
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(05)67625-8 Thatcher et al. 2005 (ISEL)]
 +
|NR
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[Non-small_cell_lung_cancer_-_null_regimens#Placebo_5|Placebo]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|[https://doi.org/10.1016/S0140-6736(08)61758-4 Kim et al. 2008 (INTEREST)]
 +
|2004-2006
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior OS
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/16/4/1307.long Lee et al. 2010 (ISTANA)]
 +
|2005-2006
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#91cf60" |Seems to have superior PFS
 +
|-
 +
|[http://clincancerres.aacrjournals.org/content/17/6/1553.long Han et al. 2011 (NCCCTS-06-177)]
 +
|2006-2008
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Gefitinib_.26_Simvastatin_99|Gefitinib & Simvastatin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70355-3 Shi et al. 2013 (ICOGEN)]
 +
|2009
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Icotinib_monotherapy|Icotinib]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior PFS
 +
|-
 +
|}
 +
''Note: IDEAL2 was the basis of initial FDA approval in 2003.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Gefitinib (Iressa)]] 250 mg PO once per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''IDEAL2:''' Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. [http://jama.jamanetwork.com/article.aspx?articleid=197532 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14570950 PubMed]
 +
#'''ISEL:''' Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37. [https://doi.org/10.1016/S0140-6736(05)67625-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16257339 PubMed] NCT00242801
 +
#'''INTEREST:''' Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [https://doi.org/10.1016/S0140-6736(08)61758-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19027483 PubMed] NCT00076388
 +
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/151 Project Data Sphere]
 +
#'''ISTANA:''' Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW. Randomized phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010 Feb 15;16(4):1307-14. Epub 2010 Feb 9. [http://clincancerres.aacrjournals.org/content/16/4/1307.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20145166 PubMed] NCT00478049
 +
#'''NCCCTS-06-177:''' Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, Kim HT, Lee JS. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011 Mar 15;17(6):1553-60. [http://clincancerres.aacrjournals.org/content/17/6/1553.long link to orinigal article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21411446 PubMed] NCT00452244
 +
#'''ICOGEN:''' Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. [https://doi.org/10.1016/S1470-2045(13)70355-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23948351 PubMed] NCT01040780
 +
==Gemcitabine monotherapy {{#subobject:63e7a9|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 1000 mg/m<sup>2</sup> {{#subobject:dda826|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ Katakami et al. 2017 (E7389-G000-302)]
 +
|2011-2014 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Eribulin_monotherapy_99|Eribulin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 9.5 vs 9.5 mo<br>(HR 0.86, 95% CI 0.71-1.05)
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.02.006 Planchard et al. 2020 (ARCTIC)]
 +
|rowspan=2|2015-2016
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Durvalumab_.26_Tremelimumab_77|Durvalumab & Tremelimumab]]
 +
| style="background-color:#fee08b" |Might have inferior PFS
 +
|-
 +
|2. [[#Durvalumab_monotherapy_99|Durvalumab]]<br>3. [[#Tremelimumab_monotherapy_77|Tremelimumab]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 +
'''28-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 1250 mg/m<sup>2</sup> {{#subobject:7f2a5c|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ Katakami et al. 2017 (E7389-G000-302)]
 +
|2011-2014 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Eribulin_monotherapy_99|Eribulin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 9.5 vs 9.5 mo<br>(HR 0.86, 95% CI 0.71-1.05)
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''E7389-G000-302:''' Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. [https://doi.org/10.1093/annonc/mdx284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911085 PubMed] NCT01454934
 +
#'''ARCTIC:''' Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. Epub 2020 Feb 20. [https://doi.org/10.1016/j.annonc.2020.02.006 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32201234 PubMed] NCT02352948
 +
==Icotinib monotherapy {{#subobject:9720a1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:d7253b|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70355-3 Shi et al. 2013 (ICOGEN)]
 +
|2009
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Gefitinib_monotherapy_3|Gefitinib]]
 +
| style="background-color:#eeee01" |Seems to have non-inferior PFS
 +
|-
 +
|}
 +
''Note: this drug is only approved in China.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Icotinib (Conmana)]] 125 mg PO three times per day
 +
'''Continued indefinitely'''
 +
</div></div>
 +
===References===
 +
#'''ICOGEN:''' Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. [https://doi.org/10.1016/S1470-2045(13)70355-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23948351 PubMed] NCT01040780
 +
==Nivolumab monotherapy {{#subobject:7e5a40|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:f73cfc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1093/annonc/mdi403 Diviné et al. 2005 (LMB95)]
+
|[https://doi.org/10.1016/j.jtho.2019.01.006 Wu et al. 2019 (CheckMate 078)]
−
|1996-2001
+
|2015-2016
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 11.9 vs 9.5 mo<br>(HR 0.75, 95% CI 0.61-0.93)
 
|-
 
|-
 
|}
 
|}
−
''Note: This regimen is for group B (unresected stage I, non-abdominal stage II and any stage III or IV disease without CNS or bone marrow involvement).
+
''<sup>1</sup>Reported efficacy is based on the 2020 update.''
−
<div class="toccolours" style="background-color:#cbd5e8">
+
<div class="toccolours" style="background-color:#fdcdac">
−
====Preceding treatment====
+
====Prior treatment criteria====
−
*[[#Cytarabine_.26_Methotrexate_.28CYM.29|CYM]] consolidation
+
*Failure of a [[Regimen_classes#Platinum_doublet|platinum doublet]]
 
</div>
 
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 +
**Notably, on 9/13/16 the [http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm520871.htm FDA recommended] that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.
 +
'''14-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''CheckMate 078:''' Wu YL, Lu S, Cheng Y, Zhou C, Wang J, Mok T, Zhang L, Tu HY, Wu L, Feng J, Zhang Y, Luft AV, Zhou J, Ma Z, Lu Y, Hu C, Shi Y, Baudelet C, Cai J, Chang J. Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial. J Thorac Oncol. 2019 May;14(5):867-875. Epub 2019 Jan 17. [https://doi.org/10.1016/j.jtho.2019.01.006 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30659987 PubMed] NCT02613507
 +
##'''Update:''' Lu S, Wang J, Cheng Y, Mok T, Chang J, Zhang L, Feng J, Tu HY, Wu L, Zhang Y, Luft A, Zhou JY, Ma Z, Lu Y, Hu C, Shi Y, Ying K, Zhong H, Poddubskaya E, Soo RA, Chia YH, Li A, Li A, Wu YL. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078). Lung Cancer. 2021 Feb;152:7-14. Epub 2020 Nov 24. [https://doi.org/10.1016/j.lungcan.2020.11.013 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33321441/ PubMed]
 +
==nab-Paclitaxel monotherapy {{#subobject:8f6227|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:fe2978|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1016/j.jtho.2021.03.027 Yoneshima et al. 2021 (J-AXEL)]
 +
|2015-2018
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''J-AXEL:''' Yoneshima Y, Morita S, Ando M, Nakamura A, Iwasawa S, Yoshioka H, Goto Y, Takeshita M, Harada T, Hirano K, Oguri T, Kondo M, Miura S, Hosomi Y, Kato T, Kubo T, Kishimoto J, Yamamoto N, Nakanishi Y, Okamoto I. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol. 2021 Sep;16(9):1523-1532. Epub 2021 Apr 27. [https://doi.org/10.1016/j.jtho.2021.03.027 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33915251/ PubMed]
 +
==Pembrolizumab monotherapy {{#subobject:068cc1|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #1, 2 mg/kg {{#subobject:d2e0eb|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1501824 Garon et al. 2015 (KEYNOTE-001)]
 +
|2012-2014
 +
| style="background-color:#91cf61" |Phase 1, >20 pts in dosing cohort
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/S0140-6736(15)01281-7 Herbst et al. 2015 (KEYNOTE-010)]
 +
|rowspan=2|2013-2015
 +
|rowspan=2 style="background-color:#1a9851" |Phase 2/3 (E-RT-switch-ooc)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.4 vs 8.5 mo<br>(HR 0.71, 95% CI 0.58-0.88)
 +
|-
 +
|2. [[#Pembrolizumab_monotherapy_4|Pembrolizumab]]; 10 mg/kg
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
''Note: patients had previously received chemotherapy.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 2 mg/kg IV once on day 1
 +
'''21-day cycles'''
 +
</div></div><br>
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen variant #2, 10 mg/kg {{#subobject:d2jghc|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1501824 Garon et al. 2015 (KEYNOTE-001)]
 +
|2012-2014
 +
| style="background-color:#91cf61" |Phase 1, >20 pts in dosing cohort
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#d3d3d3" |
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/S0140-6736(15)01281-7 Herbst et al. 2015 (KEYNOTE-010)]
 +
|rowspan=2|2013-2015
 +
|rowspan=2 style="background-color:#1a9851" |Phase 2/3 (E-RT-switch-ooc)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#1a9850" |Superior OS<br>Median OS: 12.7 vs 8.5 mo<br>(HR 0.61, 95% CI 0.49-0.75)
 +
|-
 +
|2. [[#Pembrolizumab_monotherapy_4|Pembrolizumab]]; 2 mg/kg
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
''Note: patients had previously received chemotherapy.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Pembrolizumab (Keytruda)]] 10 mg/kg IV once on day 1
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''KEYNOTE-001:''' Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. [https://doi.org/10.1056/NEJMoa1501824 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25891174 PubMed] NCT01295827
 +
#'''KEYNOTE-010:''' Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [https://doi.org/10.1016/S0140-6736(15)01281-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26712084 PubMed] NCT01905657
 +
##'''Update:''' Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020 May 10;38(14):1580-1590. Epub 2020 Feb 20. [https://doi.org/10.1200/jco.19.02446 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32078391/ PubMed]
 +
==Pemetrexed monotherapy {{#subobject:24ad9b|Regimen=1}}==
 +
===Example orders===
 +
*[[Example orders for Pemetrexed (Alimta) in non-small cell lung cancer]]
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4e0d06|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/jco.2004.08.163 Hanna et al. 2004 (JMEI)]
 +
|2001-2002
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 +
|-
 +
|[https://doi.org/10.1016/S1470-2045(13)70473-X Kim et al. 2013 (JXBC)]
 +
|2005-2010
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Stub#Pemetrexed_.26_Cetuximab|Pemetrexed & Cetuximab]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 2.8 vs 2.9 mo<br>(HR 0.97, 95% CI 0.83-1.15)
 +
|-
 +
|[https://doi.org/full/10.1002/cncr.28132 Karampeazis et al. 2013 (CT/06.05)]
 +
|2006-2010
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 +
|[[Non-small_cell_lung_cancer_-_historical#Erlotinib_monotherapy_2|Erlotinib]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ Katakami et al. 2017 (E7389-G000-302)]
 +
|2011-2014 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Eribulin_monotherapy_99|Eribulin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 9.5 vs 9.5 mo<br>(HR 0.86, 95% CI 0.71-1.05)
 +
|-
 +
|}
 +
''Note: JXBC also evaluated docetaxel versus docetaxel & cetuximab, but did not report the efficacy of this comparison; see paper for details.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
 +
====Supportive therapy====
 +
*(per Ardizzoni et al. 2012):
 +
*[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
 +
*[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
 +
**JMEI used [[Folic acid (Folate)]] 1 mg PO once per day
 +
*[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be given throughout pemetrexed therapy
 +
'''21-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''JMEI:''' Hanna N, Shepherd FA, Fossella FV, Rodrigues Pereira J, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar M, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [https://doi.org/10.1200/jco.2004.08.163 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15117980 PubMed]
 +
#'''CT/06.05:''' Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. [https://doi.org/full/10.1002/cncr.28132 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23661337 PubMed] NCT00440414
 +
#'''JXBC:''' Kim ES, Neubauer M, Cohn A, Schwartzberg L, Garbo L, Caton J, Robert F, Reynolds C, Katz T, Chittoor S, Simms L, Saxman S. Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. Lancet Oncol. 2013 Dec;14(13):1326-36. Epub 2013 Nov 12. Erratum in: Lancet Oncol. 2014 Jan;15(1):e4. [https://doi.org/10.1016/S1470-2045(13)70473-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24231627 PubMed] NCT00095199
 +
#'''E7389-G000-302:''' Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. [https://doi.org/10.1093/annonc/mdx284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911085 PubMed] NCT01454934
 +
==S-1 monotherapy {{#subobject:7702f2|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:48e547|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834128/ Nokihara et al. 2017 (EAST-LC)]
 +
|2010-2014
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Docetaxel_monotherapy_4|Docetaxel]]
 +
| style="background-color:#eeee01" |Non-inferior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 +
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
 +
**BSA at least 1.25 m<sup>2</sup> and less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
 +
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
 +
'''42-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''EAST-LC:''' Nokihara H, Lu S, Mok TSK, Nakagawa K, Yamamoto N, Shi YK, Zhang L, Soo RA, Yang JC, Sugawara S, Nishio M, Takahashi T, Goto K, Chang J, Maemondo M, Ichinose Y, Cheng Y, Lim WT, Morita S, Tamura T. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol. 2017 Nov 1;28(11):2698-2706. [https://doi.org/10.1093/annonc/mdx419 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834128/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29045553 PubMed] JapicCTI-101155
 +
==Vinorelbine monotherapy {{#subobject:f604bd|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:0441ba|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |Years of enrollment
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
| rowspan="2" |[https://doi.org/10.1200/JCO.2000.18.12.2354 Fossella et al. 2000 (TAX 320)]
 +
| rowspan="2" |1995-1998
 +
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Docetaxel_monotherapy_4|Docetaxel 100 mg/m<sup>2</sup>]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|2. [[#Docetaxel_monotherapy_4|Docetaxel 75 mg/m<sup>2</sup>]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ Katakami et al. 2017 (E7389-G000-302)]
 +
|2011-2014 (C)
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Eribulin_monotherapy_99|Eribulin]]
 +
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 9.5 vs 9.5 mo<br>(HR 0.86, 95% CI 0.71-1.05)
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.02.006 Planchard et al. 2020 (ARCTIC)]
 +
|rowspan=2|2015-2016
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 +
|1. [[#Durvalumab_.26_Tremelimumab_77|Durvalumab & Tremelimumab
 +
| style="background-color:#fee08b" |Might have inferior PFS
 +
|-
 +
|2. [[#Durvalumab_monotherapy_99|Durvalumab]]<br>3. [[#Tremelimumab_monotherapy_77|Tremelimumab]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|}
 +
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Cyclophosphamide (Cytoxan)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 2
+
*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV over 5 to 10 minutes once per day on days 1, 8, 15, 22
−
*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 
−
*[[Doxorubicin (Adriamycin)]] 60 mg/m<sup>2</sup> IV once on day 2
 
−
*[[Methotrexate (MTX)]] 3000 mg/m<sup>2</sup> IV over 3 hours once on day 1
 
−
====Glucocorticoid therapy====
 
−
*[[Prednisone (Sterapred)]] 60 mg/m<sup>2</sup>/day PO on days 1 to 5
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Folinic acid (Leucovorin)]] 15 mg/m<sup>2</sup> (route not specified) every 6 hours on days 2 to 4
+
*Per TAX 320:
−
====CNS therapy, prophylaxis====
+
*Patients who had either grade 4 neutropenia lasting at least 5 days or both fever and grade 3 or 4 neutropenia could receive [[:Category:Granulocyte colony-stimulating factors|G-CSF]] (dose/schedule/duration not specified)
−
*[[Methotrexate (MTX)]] 15 mg IT once on day 2
+
*[[Metoclopramide (Reglan)]] (dose/schedule/route not specified) used first for nausea
−
*[[Hydrocortisone (Cortef)]] 15 mg IT once on day 2 (admixed with MTX)
+
*Nausea despite metoclopramide was treated with a 5-HT3 antagonist such as [[Ondansetron (Zofran)]] or [[Granisetron]] (dose/schedule/route not specified) prn nausea
−
'''One course'''
+
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''TAX 320:''' Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L; TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209. [https://doi.org/10.1200/JCO.2000.18.12.2354 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10856094 PubMed]
 +
#'''E7389-G000-302:''' Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. [https://doi.org/10.1093/annonc/mdx284 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834051/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911085 PubMed] NCT01454934
 +
#'''ARCTIC:''' Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. Epub 2020 Feb 20. [https://doi.org/10.1016/j.annonc.2020.02.006 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/32201234 PubMed] NCT02352948
 +
=CNS metastases, all lines of therapy=
 +
==Dexamethasone monotherapy {{#subobject:adb3fe|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:6a5b0e|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ Mulvenna et al. 2016 (QUARTZ)]
 +
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 +
|[[#Dexamethasone_.26_WBRT|Dexamethasone & WBRT]]
 +
|
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior QALYs
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]]
 +
</div></div>
 +
===References===
 +
#'''QUARTZ:''' Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. [https://doi.org/10.1016/s0140-6736(16)30825-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27604504 PubMed] ISRCTN3826061
 +
==Dexamethasone & WBRT {{#subobject:04a6d4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:da6414|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
! style="width: 20%" |Study
 +
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 20%" |Comparator
 +
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
! style="width: 20%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ Mulvenna et al. 2016 (QUARTZ)]
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Dexamethasone_monotherapy|Dexamethasone]]
 +
|
 +
| style="background-color:#ffffbf" |Inconclusive whether non-inferior QALYs
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Radiotherapy====
 +
*[[External beam radiotherapy|WBRT]], 20 Gy in 5 fractions
 +
====Supportive therapy====
 +
*[[Dexamethasone (Decadron)]]
 +
</div></div>
 +
===References===
 +
#'''QUARTZ:''' Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. [https://doi.org/10.1016/s0140-6736(16)30825-x link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082599/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27604504 PubMed] ISRCTN3826061
 +
==Teniposide & WBRT {{#subobject:04facd4|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:19bu14|Variant=1}}===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Years of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 +
|-
 +
|[https://doi.org/10.1200/JCO.2000.18.19.3400 Postmus et al. 2000]
 +
|1989-1995
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|[[#Teniposide_monotherapy_88|Teniposide]]
 +
| style="background-color:#d9ef8b" |Might have superior OS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Teniposide (Vumon)]]
 +
====Radiotherapy====
 +
*[[External beam radiotherapy|WBRT]], 30 Gy in 10 fractions
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''LMB95:''' Diviné M, Casassus P, Koscielny S, Bosq J, Sebban C, Le Maignan C, Stamattoulas A, Dupriez B, Raphaël M, Pico JL, Ribrag V; GELA; GOELAMS. Burkitt lymphoma in adults: a prospective study of 72 patients treated with an adapted pediatric LMB protocol. Ann Oncol. 2005 Dec;16(12):1928-35. Epub 2005 Nov 10. [https://doi.org/10.1093/annonc/mdi403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16284057 PubMed]
+
#Postmus PE, Haaxma-Reiche H, Smit EF, Groen HJ, Karnicka H, Lewinski T, van Meerbeeck J, Clerico M, Gregor A, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G; European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000 Oct 1;18(19):3400-8. [https://doi.org/10.1200/JCO.2000.18.19.3400 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11013281 PubMed]
−
[[Category:Burkitt lymphoma regimens]]
+
=Investigational agents=
 +
''Drugs with some degree of promising activity in clinical trials.''
 +
[[Category:Non-small cell lung cancer regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Aggressive lymphomas]]
+
[[Category:Lung cancers]]
−
[[Category:Non-Hodgkin lymphomas]]
 

Revision as of 13:19, 17 October 2022

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Section editor transclusions Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
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Guidelines

ASCO

Older

ASCO/CCO

Current

Older

ESMO

Older

KSMO/ESMO

NCCN

Neoadjuvant therapy

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (C) 1. CP & Nivolumab
2. CVb & Nivolumab
3. DC & Nivolumab 		Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Carboplatin & Paclitaxel (CP) & Nivolumab

CP & Nivolumab: Carboplatin, Paclitaxel, Nivolumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (E-esc) 1. CP
2. CVb
3. DC 		Superior EFS
Median EFS: 31.6 vs 20.8 mo
(HR 0.63, 97.38% CI 0.43-0.91)

Superior pCR rate
24% vs 2.2%
(OR 13.94, 99% CI 3.49-55.75)

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Immunotherapy

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Cisplatin & Docetaxel (DC)

DC: Docetaxel & Cisplatin

Regimen variant #1, 60-75/75 x 3

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (C) 1. CP & Nivolumab
2. CVb & Nivolumab
3. DC & Nivolumab 		Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment


Regimen variant #2, 85/100 x 3

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pless et al. 2015 (SAKK 16/00) 2001-2012 Phase 3 (C) Cisplatin & Docetaxel, then RT Did not meet primary endpoint of EFS

Eligibility criteria

  • Stage IIIA or N2 NSCLC

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. SAKK 16/00: Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S, Gerard MA, Xyrafas A, Früh M, Cathomas R, Zippelius A, Roth A, Bijelovic M, Ochsenbein A, Meier UR, Mamot C, Rauch D, Gautschi O, Betticher DC, Mirimanoff RO, Peters S; SAKK Lung Cancer Project Group. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. 2015 Sep 12;386(9998):1049-56. Epub 2015 Aug 11. Erratum in: Lancet. 2015 Sep 12;386(9998):1040. link to original article contains dosing details in abstract PubMed NCT00030771
  2. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528
  3. CheckMate 77T: NCT04025879

Cisplatin & Docetaxel (DC) & Durvalumab

DC & Durvalumab: Docetaxel, Cisplatin, Durvalumab

Regimen

Study Years of enrollment Evidence
Rothschild et al. 2021 (SAKK 16/14) 2016-2019 Phase 2

Eligibility criteria

  • Stage IIIA(N2) NSCLC

Chemotherapy

Immunotherapy

21-day cycle for 3 cycles, then 14-day cycle for 2 cycles

Subsequent treatment

References

  1. SAKK 16/14: Rothschild SI, Zippelius A, Eboulet EI, Savic Prince S, Betticher D, Bettini A, Früh M, Joerger M, Lardinois D, Gelpke H, Mauti LA, Britschgi C, Weder W, Peters S, Mark M, Cathomas R, Ochsenbein AF, Janthur WD, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M; Swiss Group for Clinical Cancer Research (SAKK). SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol. 2021 Sep 10;39(26):2872-2880. Epub 2021 Jul 12. link to original article contains dosing details in manuscript PubMed NCT02572843

Cisplatin & Docetaxel (DC) & Nivolumab

DC & Nivolumab: Docetaxel, Cisplatin, Nivolumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (E-esc) 1. CP
2. CVb
3. DC 		Superior EFS
Median EFS: 31.6 vs 20.8 mo
(HR 0.63, 97.38% CI 0.43-0.91)

Superior pCR rate
24% vs 2.2%
(OR 13.94, 99% CI 3.49-55.75)

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

Immunotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Cisplatin & Etoposide (EP)

Regimen

Study Years of enrollment Evidence
Thomas et al. 2008 (GLCCG 01/95) 1995-2003 Non-randomized portion of phase 3 RCT

Note: abstract does not contain dosing details.

Chemotherapy

3 cycles

Subsequent treatment

References

  1. GLCCG 01/95: Thomas M, Rübe C, Hoffknecht P, Macha HN, Freitag L, Linder A, Willich N, Hamm M, Sybrecht GW, Ukena D, Deppermann KM, Dröge C, Riesenbeck D, Heinecke A, Sauerland C, Junker K, Berdel WE, Semik M; German Lung Cancer Cooperative Group. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol. 2008 Jul;9(7):636-48. Epub 2008 Jun 24. link to original article PubMed NCT00176137

Cisplatin & Gemcitabine (GC)

Regimen variant #1, 75/2000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (KEYNOTE 671) 2018-ongoing Phase 3 (C) 1. GC & Pembrolizumab
2. Pem-Cis & Pembrolizumab 		Awaiting results

Chemotherapy

21-day cycle for up to 4 cycles

Subsequent treatment


Regimen variant #2, 75/2500 x 3

Study Years of enrollment Evidence Comparator Comparative Efficacy
Scagliotti et al. 2011 (CHEST) 2000-2004 Phase 3 (E-esc) Surgery alone Superior OS
Median OS: 7.8 vs 4.8 y
(aHR 0.63, 95% CI 0.43-0.92)

Eligibility criteria

  • Stage IB to IIIA NSCLC

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment


Regimen variant #3, 75/2500 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (IMpower030) 2018-ongoing Phase 3 (C) 1. Carboplatin, nab-Paclitaxel, Atezolizumab
2. Carboplatin, Pemetrexed, Atezolizumab
3. GC & Atezolizumab
4. Pem-Cis & Atezolizumab 		Awaiting results

Chemotherapy

21-day cycle for up to 4 cycles

Subsequent treatment

References

  1. CHEST: Scagliotti GV, Pastorino U, Vansteenkiste JF, Spaggiari L, Facciolo F, Orlowski TM, Maiorino L, Hetzel M, Leschinger M, Visseren-Grul C, Torri V. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol. 2012 Jan 10;30(2):172-8. Epub 2011 Nov 28. link to original article contains dosing details in manuscript PubMed NCT00191126
  2. AEGEAN: NCT03800134
  3. KEYNOTE 671: NCT03425643
  4. IMpower030: NCT03456063

Cisplatin & Vinorelbine (CVb)

CVb: Cisplatin & Vinorelbine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (C) 1. CP & Nivolumab
2. CVb & Nivolumab
3. DC & Nivolumab 		Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Cisplatin & Vinorelbine (CVb) & Nivolumab

CVb & Nivolumab: Cisplatin, Vinorelbine, Nivolumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Forde et al. 2022 (CheckMate 816) 2017-2019 Phase 3 (E-esc) 1. CP
2. CVb
3. DC 		Superior EFS
Median EFS: 31.6 vs 20.8 mo
(HR 0.63, 97.38% CI 0.43-0.91)

Superior pCR rate
24% vs 2.2%
(OR 13.94, 99% CI 3.49-55.75)

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.

Biomarker eligibility criteria

  • CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

Immunotherapy

21-day cycle for 3 cycles

Subsequent treatment

References

  1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

Adjuvant therapy

Atezolizumab monotherapy

Regimen variant #1, q2wk

FDA-recommended dose

Note: This is not the dose/schedule used in the registration trial.

Preceding treatment

Immunotherapy

14-day cycle for 26 cycles (1 year)


Regimen variant #2, q3wk

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Felip et al. 2021 (IMpower010) 2015-2018 Phase 3 (E-RT-esc) Best supportive care Seems to have superior DFS
Median DFS: NYR vs 37.2 mo
(HR 0.81, 95% CI 0.67-0.99)

Note: Cisplatin & Pemetrexed was only offered to patients with nonsquamous histology.

Preceding treatment

Immunotherapy

21-day cycle for up to 16 cycles (1 year)


Regimen variant #3, q4wk

FDA-recommended dose

Note: This is not the dose/schedule used in the registration trial.

Preceding treatment

Immunotherapy

28-day cycle for 13 cycles (1 year)

References

  1. IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article contains dosing details in manuscript PubMed NCT02486718

Carboplatin & Paclitaxel (CP)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Strauss et al. 2008 (CALGB 9633) 1996-2003 Phase 3 (E-esc) Observation Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

References

  1. CALGB 9633: Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00002852
  2. IFCT 0002: Westeel V, Quoix E, Puyraveau M, Lavolé A, Braun D, Laporte S, Bigay-Game L, Pujol JL, Ozenne G, Rivière A, Douillard JY, Lebeau B, Debieuvre D, Poudenx M, David P, Molinier O, Zalcman G, Lemarié E, Morin F, Depierre A, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial). Eur J Cancer. 2013 Aug;49(12):2654-64. Epub 2013 Jun 1. link to original article PubMed NCT00198354

Cisplatin & Docetaxel (DC)

DC: Docetaxel & Cisplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Barlesi et al. 2015 2004-2007 Phase 3 (E-switch-ic) Cisplatin & Gemcitabine Did not meet primary endpoint of QoL
Wakelee et al. 2017 (ECOG-ACRIN E1505) 2007-2013 Phase 3 (C) 1. DC & Bevacizumab
2. GC & Bevacizumab
3. Cisplatin, Pemetrexed, Bevacizumab
4. Cisplatin, Vinorelbine, Bevacizumab 		Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles (Barlesi et al. 2015) or 4 cycles (ECOG-ACRIN E1505)

References

  1. Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article contains dosing details in manuscript PubMed
  2. ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article contains dosing details in abstract PubMed NCT00324805
  3. IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article contains dosing details in manuscript PubMed NCT02486718

Cisplatin & Etoposide (EP)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Arriagada et al. 2004 (IALT) 1995-2000 Phase 3 (E-esc) Observation Seems to have superior OS
OS60: 44.5% vs 40.4%
(HR 0.86, 95% CI 0.76-0.98)

Preceding treatment

Chemotherapy

28-day cycle for 4 cycles

References

  1. IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed NCT00002823
    1. Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed

Cisplatin & Gemcitabine (GC)

GC: Gemcitabine & Cisplatin

Regimen variant #1, 75/1200 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wakelee et al. 2017 (ECOG-ACRIN E1505) 2007-2013 Phase 3 (C) 1. DC & Bevacizumab
2. GC & Bevacizumab
3. Cisplatin, Pemetrexed, Bevacizumab
4. Cisplatin, Vinorelbine, Bevacizumab 		Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #2, 75/1250 x 3

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Barlesi et al. 2015 2004-2007 Phase 3 (E-switch-ic) Cisplatin & Docetaxel Did not meet primary endpoint of QoL

Eligibility criteria

  • Stage IB–III NSCLC

Preceding treatment

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #3, 75/1250 x 4

Study Years of enrollment Evidence
Felip et al. 2021 (IMpower010) 2015-2018 Non-randomized portion of phase 3 RCT

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment

References

  1. Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article contains dosing details in manuscript PubMed
  2. ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article contains dosing details in abstract PubMed NCT00324805
  3. IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article contains dosing details in manuscript PubMed NCT02486718
  4. ACCIO: NCT04267848

Cisplatin & Pemetrexed

CPx: Cisplatin & Pemetrexed

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Kreuter et al. 2013 (TREAT) 2006-2009 Randomized Phase 2 (E-switch-ic) Cisplatin & Vinorelbine Did not meet secondary endpoint of OS1 Superior clinical feasibility rate
Wakelee et al. 2017 (ECOG-ACRIN E1505) 2007-2013 Phase 3 (C) 1. DC & Bevacizumab
2. GC & Bevacizumab
3. Cisplatin, Pemetrexed, Bevacizumab
4. Cisplatin, Vinorelbine, Bevacizumab 		Did not meet primary endpoint of OS
Groen et al. 2019 (NVALT-8) 2007-2013 Phase 3 (C) CPx & Nadroparin Did not meet primary endpoint of RFS

1Reported efficacy for TREAT is based on the 2016 update.
Note: In TREAT, this treatment was intended for pathologically confirmed NSCLC stages (according to the TNM staging system version 6) IB, IIA, IIB or T3N1.

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles

References

  1. TREAT: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG Leuven Lung Cancer Group. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article contains dosing details in manuscript PubMed NCT00349089
    1. Update: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. link to original article PubMed
  2. ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article contains dosing details in abstract PubMed NCT00324805
  3. NVALT-8: Groen HJM, van der Heijden EHFM, Klinkenberg TJ, Biesma B, Aerts J, Verhagen A, Kloosterziel C, Pieterman R, van den Borne B, Smit HJM, Hoekstra O, Schramel FMNH, van der Noort V, van Tinteren H, Smit EF, Dingemans AC; NVALT Study Group. Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study. Br J Cancer. 2019 Aug;121(5):372-377. Epub 2019 Jul 24. link to original article contains dosing details in manuscript PubMed NTR1250/1217
  4. IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article contains dosing details in manuscript PubMed NCT02486718

Cisplatin & Vinblastine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Arriagada et al. 2004 (IALT) 1995-2000 Phase 3 (E-esc) Observation Seems to have superior OS
OS60: 44.5% vs 40.4%
(HR 0.86, 95% CI 0.76-0.98)

Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vinblastine schedule is extrapolated from regimen information in Table 1 in which vinblastine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.

Preceding treatment

Chemotherapy

12-week course

References

  1. IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed NCT00002823
    1. Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed

Cisplatin & Vindesine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Arriagada et al. 2004 (IALT) 1995-2000 Phase 3 (E-esc) Observation Seems to have superior OS
OS60: 44.5% vs 40.4%
(HR 0.86, 95% CI 0.76-0.98)

Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vindesine schedule is extrapolated from regimen information in Table 1 in which vindesine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.

Preceding treatment

Chemotherapy

12-week course

References

  1. IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed NCT00002823
    1. Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed

Cisplatin & Vinorelbine (CVb)

CVb: Cisplatin & Vinorelbine

Regimen variant #1, cisplatin 50 mg/m2, 2 weeks out of 4

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Winton et al. 2005 (JBR.10) 1994-2001 Phase 3 (E-esc) Observation Superior OS
Median OS: 94 vs 73 mo
(HR 0.69, 95% CI 0.52-0.91)
Kreuter et al. 2013 (TREAT) 2006-2009 Randomized Phase 2 (C) Cisplatin & Pemetrexed Did not meet secondary endpoint of OS1 Superior clinical feasibility rate

1Reported efficacy for TREAT is based on the 2016 update.

Preceding treatment

Chemotherapy

28-day cycle for 4 cycles


Regimen variant #2, cisplatin 75 mg/m2, q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wakelee et al. 2017 (ECOG-ACRIN E1505) 2007-2013 Phase 3 (C) 1. DC & Bevacizumab
2. GC & Bevacizumab
3. Cisplatin, Pemetrexed, Bevacizumab
4. Cisplatin, Vinorelbine, Bevacizumab 		Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #3, cisplatin 100 mg/m2, q4wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Douillard et al. 2006 (ANITA) 1994-2000 Phase 3 (E-esc) Observation Seems to have superior OS
Arriagada et al. 2004 (IALT) 1995-2000 Phase 3 (E-esc) Observation Seems to have superior OS
OS60: 44.5% vs 40.4%
(HR 0.86, 95% CI 0.76-0.98)

Preceding treatment

Chemotherapy

28-day cycle for 4 cycles

References

  1. IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed NCT00002823
    1. Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed
  2. JBR.10: Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. link to original article PubMed NCT00002583
    1. Update: Butts CA, Ding K, Seymour L, Twumasi-Ankrah P, Graham B, Gandara D, Johnson DH, Kesler KA, Green M, Vincent M, Cormier Y, Goss G, Findlay B, Johnston M, Tsao MS, Shepherd FA. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol. 2010 Jan 1;28(1):29-34. Epub 2009 Nov 23. link to original article link to PMC article PubMed
  3. ANITA: Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Rodrigues Pereira J, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. link to original article PubMed NCT00576914
  4. TREAT: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article contains dosing details in manuscript PubMed NCT00349089
    1. Update: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. link to original article PubMed
  5. ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article contains dosing details in abstract PubMed NCT00324805
  6. IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article contains dosing details in manuscript PubMed NCT02486718

Pembrolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
O'Brien et al. 2022 (PEARLS) 2016-2020 Phase 3 (E-esc) Placebo Superior DFS
Median DFS: 53.6 vs 42 mo
(HR 0.76, 95% CI 0.63-0.91)

Preceding treatment

Immunotherapy

21-day cycle for up to 18 cycles

References

  1. PEARLS: O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, Esteban E, Isla D, Martinez-Marti A, Faehling M, Tsuboi M, Lee JS, Nakagawa K, Yang J, Samkari A, Keller SM, Mauer M, Jha N, Stahel R, Besse B, Peters S; EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Sep 9. Epub ahead of print. link to original article contains dosing details in abstract PubMed NCT02504372

Radiation therapy

RT: Radiation Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (KEYNOTE-867) 2019-ongoing Phase 3 (C) Pembrolizumab & RT Awaiting results
Awaiting publication (PACIFIC-4) 2019-ongoing Phase 3 (C) Durvalumab & RT Awaiting results
Awaiting publication (SWOG S1914) 2020-ongoing Phase 3 (C) Atezolizumab & RT Awaiting results

Radiotherapy

References

  1. KEYNOTE-867: NCT03924869
  2. PACIFIC-4: NCT03833154
  3. SWOG S1914: NCT04214262

Tegafur & uracil monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Yamaguchi et al. 2021 (WJTOG0101) 2001-2005 Phase 3 (C) Gemcitabine Did not meet primary endpoint of OS
OS60: 68.8% vs 70%
(HR 1.05, 95% CI 0.81-1.37)

Eligibility criteria

  • Stage IB-IIIA NSCLC, with complete resection

Preceding treatment

Chemotherapy

1-year course

References

  1. WJTOG0101: Yamaguchi M, Tada H, Mitsudomi T, Seto T, Yokoi K, Katakami N, Nakagawa K, Oda M, Ohta M, Sawa T, Yamashita M, Iked N, Saka H, Higashiyama M, Nomori H, Semba H, Negoro S, Chiba Y, Shimokawa M, Fukuoka M, Nakanishi Y; West Japan Thoracic Oncology Group (WJTOG). Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101). Int J Clin Oncol. 2021 Dec;26(12):2216-2223. Epub 2021 Aug 31. link to original article contains dosing details in manuscript PubMed NCT00139971

Induction chemotherapy for locally advanced disease

Carboplatin & Paclitaxel (CP)

PC: Paclitaxel & Carboplatin

Regimen variant #1, 6/200

Study Years of enrollment Evidence Comparator Comparative Efficacy
Huber et al. 2006 (CTRT99/97) 1997-2002 Non-randomized portion of phase 3 RCT
Belani et al. 2005 (LAMP) 1998-2001 Phase 2
Vokes et al. 2007 (CALGB 39801) 1998-2002 Phase 3 (E-esc) No induction Did not meet primary endpoint of OS50%

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 2 cycles

Subsequent treatment


Regimen variant #2, 6/225

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hoang et al. 2012 (ECOG 3598) 2000-2006 Phase 3 (C) See link See link

Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

21-day cycle for 2 cycles

Subsequent treatment

References

  1. LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains dosing details in abstract PubMed
  2. CTRT99/97: Huber RM, Flentje M, Schmidt M, Pöllinger B, Gosse H, Willner J, Ulm K; Bronchial Carcinoma Therapy Group. Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group. J Clin Oncol. 2006 Sep 20;24(27):4397-404. link to original article contains dosing details in abstract PubMed
  3. CALGB 39801: Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; CALGB. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. link to original article contains dosing details in abstract PubMed NCT00003387
  4. ECOG 3598: Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00004859

Cisplatin & Vinblastine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Dillman et al. 1990 (CALGB 8433) 1984-1987 Phase 3 (E-esc) No induction Seems to have superior OS1
Sause et al. 1995 (RTOG 88-08) 1989-1992 Phase 3 (E-esc) No induction Seems to have superior OS
Curran et al. 2011 (RTOG 9410) 1994-1998 Phase 3 (C) See link See link

1Reported efficacy for CALGB 8433 is based on the 1996 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.

Chemotherapy

5-week course

Subsequent treatment

  • RT x 60 to 63 Gy

References

  1. CALGB 8433: Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, Carey RW, Frei EF 3rd, Green MR. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990 Oct 4;323(14):940-5. link to original article contains dosing details in abstract PubMed
    1. Update: Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst. 1996 Sep 4;88(17):1210-5. link to original article PubMed
  2. RTOG 88-08: Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran WJ, Byhardt RW, Turrisi AT, Dar AR, Cox JD. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst. 1995 Feb 1;87(3):198-205. link to original article contains dosing details in abstract PubMed
    1. Update: Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A 3rd. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000 Feb;117(2):358-64. link to original article PubMed
  3. RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed NCT01134861

Definitive therapy for locally advanced disease

Carboplatin & Paclitaxel (CP) & RT

CP & RT: Carboplatin, Paclitaxel, Radiation Therapy
PC & RT: Paclitaxel, Carboplatin, Radiation Therapy

Regimen variant #1, 2/40/60

Study Years of enrollment Evidence Comparator Comparative Efficacy
Yamamoto et al. 2010 (WJTOG0105) 2001-2005 Phase 3 (E-switch-ic) 1. MVP & RT
2. Carboplatin, Irinotecan, RT 		Inconclusive whether non-inferior OS

Chemotherapy

Radiotherapy

6-week course


Regimen variant #2, 2/45/60

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lu et al. 2010 (ID99-303) 2000-2006 Phase 3 (C) PC, AE-941, RT Did not meet primary endpoint of OS
Hoang et al. 2012 (ECOG 3598) 2000-2006 Phase 3 (C) See link See link
Bradley et al. 2015 (RTOG 0617) 2007-2011 Phase 3 (C) 1. CP, Cetuximab, concurrent RT Did not meet primary endpoint of OS
2. CP & RT; high-dose RT
3. CP, Cetuximab, RT; high-dose RT 		Superior OS
Liang et al. 2017 2007-2011 Phase 3 (C) EP & RT Might have inferior OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Preceding treatment

  • ECOG 3598: PC induction x 2

Chemotherapy

21-day cycle for 2 cycles

Radiotherapy

6-week course

Subsequent treatment

  • RTOG 0617: PC consolidation x 2

Regimen variant #3, 2/45/63

Study Evidence
Belani et al. 2005 (LAMP) Phase 2

Preceding treatment

  • PC induction

Chemotherapy

21-day cycle for 2 cycles

Radiotherapy

  • Concurrent radiation therapy: 1.8 Gy fractions x 25 fractions, then 2 Gy fractions x 9 fractions

7-week course

Subsequent treatment

  • PC consolidation x 2

Regimen variant #4, 2/50/66

Study Evidence
Vokes et al. 2007 (CALGB 39801) Non-randomized portion of phase 3 RCT

Preceding treatment

Chemotherapy

  • Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, given second
  • Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, given first

Radiotherapy

7-week course

References

  1. LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains dosing details in abstract PubMed
  2. CALGB 39801: Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; CALGB. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. link to original article contains dosing details in manuscript PubMed NCT00003387
  3. ID99-303: Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst. 2010 Jun 16;102(12):859-65. Epub 2010 May 26. link to original article link to PMC article contains dosing details in abstract PubMed NCT00005838
  4. WJTOG0105: Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. link to original article contains dosing details in abstract PubMed NCT00144053
    1. Update: Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Ymamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. link to original article link to PMC article PubMed
  5. ECOG 3598: Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00004859
  6. RTOG 0617: Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00533949
    1. Update: Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. link to original article link to PMC article PubMed
    2. Dataset: Project Data Sphere
  7. Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. link to original article contains dosing details in manuscript PubMed NCT01494558
  8. ECOG E5181: NCT04092283
  9. MS200647_0005: NCT03840902
  10. PACIFIC 2: NCT03519971

Carboplatin, Vinorelbine, RT

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Strøm et al. 2013 (Conrad) 2006-2011 Phase 3 (E-esc) Carboplatin & Vinorelbine Superior OS

Chemotherapy

21-day cycle for 4 cycles

Radiotherapy

References

  1. Conrad: Strøm HH, Bremnes RM, Sundstrøm SH, Helbekkmo N, Fløtten O, Aasebø U; Norwegian Lung Cancer Study Group. Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2013 Sep 17;109(6):1467-75. Epub 2013 Aug 20. link to original article link to PMC article contains dosing details in manuscript PubMed ISRCTN63778716

Carboplatin & RT

Carboplatin & RT: Carboplatin & Radiation Therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Atagi et al. 2012 (JCOG0301) 2003-2010 Phase 3 (E-esc) RT Seems to have superior OS

Chemotherapy

Radiotherapy

References

  1. JCOG0301: Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; JCOG Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. link to original article contains dosing details in abstract PubMed NCT00132665

Cisplatin & RT

Cisplatin & RT: Cisplatin & Radiation Therapy

Regimen variant #1

Study Years of enrollment Evidence Comparator Comparative Efficacy
Schaake-Koning et al. 1992 1984-1989 Phase 3 (E-esc) 1. Cisplatin & RT; weekly cisplatin Did not meet primary endpoint of OS
2. RT Superior OS

Chemotherapy

Radiotherapy

  • Concurrent radiation therapy as follows:
    • Weeks 1 & 2: 3 Gy fractions, five fractions per week
    • Weeks 3 to 5: no radiation
    • Weeks 6 & 7: 2.5 Gy fractions, five fractions per week

7-week course


Regimen variant #2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Blanke et al. 1995 1986-1992 Phase 3 (E-esc) RT Might have superior PFS

Chemotherapy

21-day cycle for 3 cycles

Radiotherapy

  • Concurrent radiation therapy 60 to 65 Gy total tumor dose in daily fractions of 1.8 to 2 Gy

6-week course

References

  1. Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, Renaud A, Rodrigus P, Schuster-Uitterhoeve L, Sculier JP, van Zandwijk N, Bartelink H. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992 Feb 20;326(8):524-30. link to original article contains dosing details in abstract PubMed
  2. Blanke C, Ansari R, Mantravadi R, Gonin R, Tokars R, Fisher W, Pennington K, O'Connor T, Rynard S, Miller M, Einhorn L. Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol. J Clin Oncol. 1995 Jun;13(6):1425-9. link to original article contains dosing details in abstract PubMed

Cisplatin, Docetaxel, RT

DC & RT: Docetaxel, Cisplatin, Radiation Therapy
DP & RT: Docetaxel, Platinol (Cisplatin), Radiation Therapy

Regimen variant #1, 20/20

Study Years of enrollment Evidence Comparator Comparative Efficacy
Oh et al. 2013 (KASLC 0401) 2005-2007 Phase 3 (C) 1. TP & RT
2. GC & RT 		Did not meet primary endpoint of ORR
Ahn et al. 2015 (KCSG-LU05-04) 2005-2011 Non-randomized portion of phase 3 RCT

In KCSG-LU05-04, no benefit was observed to giving post-definitive consolidation.

Chemotherapy

Radiotherapy

6-week course

Subsequent treatment


Regimen variant #2, 40/40

Study Years of enrollment Evidence Comparator Comparative Efficacy
Segawa et al. 2010 (OLCSG 0007) 2000-2005 Phase 3 (E-switch-ic) MVP & RT Might have superior OS

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

References

  1. OLCSG 0007: Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, Kanazawa S, Takata I, Nogami N, Hotta K, Hiraki A, Tabata M, Matsuo K, Tanimoto M. Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010 Jul 10;28(20):3299-306. Epub 2010 Jun 7. link to original article contains dosing details in abstract PubMed UMIN000000085
  2. KASLC 0401: Oh IJ, Kim KS, Kim YC, Ban HJ, Kwon YS, Kim YI, Lim SC, Chung WK, Nam TK, Song JY, Yoon MS, Ahn SJ. A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. Cancer Chemother Pharmacol. 2013 Dec;72(6):1247-54. Epub 2013 Oct 5. link to original article contains dosing details in abstract PubMed
  3. KCSG-LU05-04: Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol. 2015 Aug 20;33(24):2660-6. Epub 2015 Jul 6. link to original article contains dosing details in manuscript PubMed NCT00326378

Cisplatin, Etoposide, RT

EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy

Regimen variant #1, 45 Gy with response-adapted treatment

Study Years of enrollment Evidence
Albain et al. 2002 (SWOG 9019) 1992-1995 Phase 2
Albain et al. 2009 (RTOG 93-09) 1994-2001 Non-randomized portion of phase 3 RCT

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

  • Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), to start within 24 hours of cycle 1 day 1

5-week course

Subsequent treatment

  • SWOG 9019: Patients were re-imaged with CT scan (bone scan and head imaging were only done if patients had new symptoms), and those without progression or new metastatic disease received an additional 2 Gy per day x 8 fractions for a total of 61 Gy administered overall
  • RTOG 93-09: Additional radiation to 61 Gy, then cisplatin & etoposide consolidation versus surgery, then cisplatin & etoposide consolidation

Regimen variant #2, 60 to 66 Gy

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kelly et al. 2008 (SWOG S0023) 2001-2005 Non-randomized portion of phase 3 RCT
Hanna et al. 2008 (HOG Lun 01-24) 2002-2006 Non-randomized portion of phase 3 RCT
Liang et al. 2017 2007-2011 Phase 3 (C) PC & RT Might have superior OS

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

  • Concurrent radiation therapy, 1.8 to 2 Gy fractions x 30 to 33 fractions (total dose: 60 to 66 Gy)

6- to 6.5-week course

Subsequent treatment


Regimen variant #3, 66 Gy, split cisplatin

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fournel et al. 2005 (NPC 95-01) 1996-2000 Phase 3 (E-switch-ic) Cisplatin & Vinorelbine, then RT Did not meet primary endpoint of OS

Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

6.5-week course

Subsequent treatment


Regimen variant #4, 69.6 Gy (hyperfractionated)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Curran et al. 2011 (RTOG 9410) 1994-1998 Phase 3 (E-switch-ic) 1. Cisplatin, Vinblastine, RT Did not meet primary endpoint of OS
2. Cisplatin & Vinblastine, then RT Might have superior OS

Chemotherapy

28-day cycle for 2 cycles

Radiotherapy

  • Concurrent radiation therapy, 1.2 Gy fractions (total dose: 69.6 Gy), given twice per day for 5 days per week, starting on cycle 1 day 1

References

  1. SWOG 9019: Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. link to original article contains dosing details in abstract PubMed
  2. Schild SE, Stella PJ, Geyer SM, Bonner JA, Marks RS, McGinnis WL, Goetz SP, Kuross SA, Mailliard JA, Kugler JW, Schaefer PL, Jett JR. Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):370-8. link to original article PubMed
  3. NPC 95-01: Fournel P, Robinet G, Thomas P, Souquet PJ, Léna H, Vergnenégre A, Delhoume JY, Le Treut J, Silvani JA, Dansin E, Bozonnat MC, Daurés JP, Mornex F, Pérol M; Groupe Lyon-Saint-Etienne d'Oncologie Thoracique; Groupe Français de Pneumo-Cancérologie. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol. 2005 Sep 1;23(25):5910-7. Epub 2005 Aug 8. link to original article contains dosing details in abstract PubMed
  4. SWOG S0023: Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, Lau DH, Crowley JJ, Gandara DR. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008 May 20;26(15):2450-6. Epub 2008 Mar 31. link to original article contains dosing details in manuscript PubMed NCT00020709
  5. HOG Lun 01-24: Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and U.S. Oncology. J Clin Oncol. 2008 Dec 10;26(35):5755-60. Epub 2008 Nov 10. link to original article contains dosing details in abstract PubMed NCT00216125
  6. RTOG 93-09: Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009 Aug 1;374(9687):379-86. Epub 2009 Jul 24. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00002550
  7. RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed NCT01134861
  8. Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. link to original article contains dosing details in manuscript PubMed NCT01494558
  9. MS200647_0005: NCT03840902
  10. PACIFIC 2: NCT03519971

Cisplatin, Pemetrexed, RT

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (MS200647_0005) 2019-ongoing Phase 3 (C) 1. CP, Bintrafusp alfa, RT
2. Cisplatin, Pemetrexed, Bintrafusp alfa, RT
3. EP, Bintrafusp alfa, RT 		TBD

Chemotherapy

21-day cycle for 3 cycles

Radiotherapy

  • Concurrent IMRT, 2 Gy fractions x 30 (total dose: 60 Gy)

6-week course

Subsequent treatment

References

  1. MS200647_0005: contains dosing details on CT.gov NCT03840902

Cisplatin, Vinblastine, RT

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Curran et al. 2011 (RTOG 9410) 1994-1998 Phase 3 (E-switch-ic) 1. Cisplatin, Etoposide, RT Did not meet primary endpoint of OS
2. Cisplatin & Vinblastine, then RT Seems to have superior OS

Chemotherapy

Radiotherapy

5-week course

References

  1. RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed NCT01134861

Cisplatin, Vinorelbine, RT

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Eberhardt et al. 2015 (ESPATUE) 2004-2013 Phase 3 (E-switch-ooc) Surgery Did not meet primary endpoint of OS

Preceding treatment

Chemotherapy

Radiotherapy

21-day course

References

  1. ESPATUE: Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V, Welter S, Budach W, Spengler W, Kimmich M, Fischer B, Schmidberger H, De Ruysscher D, Belka C, Cordes S, Hepp R, Lütke-Brintrup D, Lehmann N, Schuler M, Jöckel KH, Stamatis G, Stuschke M. Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE). J Clin Oncol. 2015 Dec 10;33(35):4194-201. Epub 2015 Nov 2. link to original article contains dosing details in abstract PubMed

Radiation therapy

RT: Radiation Therapy

Regimen variant #1, 20 Gy

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ball et al. 1997 1988-1993 Phase 3 (C) 5-FU & RT Seems to have inferior OS

Radiotherapy

5-day course


Regimen variant #2, 45 Gy + 18 Gy boost (63 Gy total)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Curran et al. 2011 (RTOG 9410) 1994-1998 Phase 3 (C) See link See link
Belani et al. 2005 (LAMP) 1998-2001 Phase 2

Preceding treatment

Radiotherapy

7-week course


Regimen variant #3, 60 Gy

Study Years of enrollment Evidence Comparator Comparative Efficacy
Perez et al. 1988 NR Phase 3 (C) Levamisole & RT Did not meet endpoint of OS
Morton et al. 1991 1983-1987 Phase 3 (C) MACC & RT Did not meet primary endpoint of OS
Clamon et al. 1999 (CALGB 9130) 1991-NR Phase 3 (C) Carboplatin & RT Did not meet primary endpoint of OS
Bradley et al. 2002 (RTOG 93-04) 1994-1998 Phase 3 (C) Beta-interferon & RT Did not meet primary endpoint of OS
Groen et al. 2004 1995-1998 Phase 3 (C) Carboplatin & RT Did not meet primary endpoint of OS24
Atagi et al. 2012 (JCOG0301) 2003-2010 Phase 3 (C) Carboplatin & RT Seems to have inferior OS

Preceding treatment

Radiotherapy

One course

References

  1. Perez CA, Bauer M, Emami BN, Byhardt R, Brady LW, Doggett RL, Gardner P, Zinninger M. Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG. Int J Radiat Oncol Biol Phys. 1988 Dec;15(6):1337-46. link to original article PubMed
  2. Morton RF, Jett JR, McGinnis WL, Earle JD, Therneau TM, Krook JE, Elliott TE, Mailliard JA, Nelimark RA, Maksymiuk AW, Drummond RG, Laurie JA, Kugler JW, Anderson RT. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer: a randomized, phase III trial. Ann Intern Med. 1991 Nov 1;115(9):681-6. link to original article PubMed
  3. Ball D, Smith J, Bishop J, Olver I, Davis S, O'Brien P, Bernshaw D, Ryan G, Millward M. A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer. Br J Cancer. 1997;75(5):690-7. link to original article link to PMC article PubMed
  4. CALGB 9130: Clamon G, Herndon J, Cooper R, Chang AY, Rosenman J, Green MR; CALGB; ECOG. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol. 1999 Jan;17(1):4-11. link to original article PubMed
  5. RTOG 93-04: Bradley JD, Scott CB, Paris KJ, Demas WF, Machtay M, Komaki R, Movsas B, Rubin P, Sause WT. A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04). Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1173-9. link to original article contains dosing details in abstract PubMed
  6. Groen HJ, van der Leest AH, Fokkema E, Timmer PR, Nossent GD, Smit WJ, Nabers J, Hoekstra HJ, Hermans J, Otter R, van Putten JW, de Vries EG, Mulder NH. Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study. Ann Oncol. 2004 Mar;15(3):427-32. link to original article PubMed
  7. LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains dosing details in abstract PubMed
  8. RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article PubMed NCT01134861
  9. JCOG0301: Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; JCOG Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. link to original article contains dosing details in abstract PubMed NCT00132665
  10. SWOG S1914: NCT04214262

Consolidation or maintenance after definitive therapy for inoperable disease

Carboplatin & Paclitaxel (CP)

Regimen

Study Years of enrollment Evidence
Belani et al. 2005 (LAMP) 1998-2001 Phase 2
Bradley et al. 2015 (RTOG 0617) 2007-2011 Non-randomized portion of phase 3 RCT

Preceding treatment

Chemotherapy

21-day cycle for 2 cycles

References

  1. LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains dosing details in abstract PubMed
  2. RTOG 0617: Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00533949
    1. Update: Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. link to original article link to PMC article PubMed
    2. Dataset: Project Data Sphere

Durvalumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Antonia et al. 2017 (PACIFIC) 2014-2016 Phase 3 (E-RT-esc) Placebo Superior OS1
Median OS: 47.5 vs 29.1 mo
(HR 0.72, 95% CI 0.59-0.89)
Awaiting publication (CheckMate 73L) 2019-2025 Phase 3 (C) 1. Ipilimumab & Nivolumab
2. Nivolumab 		TBD
Awaiting publication (SKYSCRAPER-03) 2020-2024 Phase 3 (C) Atezolizumab & Tiragolumab TBD
Awaiting publication (KEYLYNK-012) 2020-2026 Phase 3 (C) 1. Olaparib & Pembrolizumab
2. Pembrolizumab 		TBD
Awaiting publication (BGB-A317-A1217-301) 2021-2025 Phase 3 (C) 1. Ociperlimab & Tislelizumab
2. Tislelizumab 		TBD
Awaiting publication (PACIFIC-9) 2022-2026 Phase 3 (C) 1. Durvalumab & Monalizumab
2. Durvalumab & Oleclumab 		TBD
Awaiting publication (PACIFIC-8) 2022-2027 Phase 3 (C) Domvanalimab & Durvalumab TBD

1Reported efficacy is based on the 2022 update.

Preceding treatment

  • PACIFIC: "Two or more cycles (defined according to local practice) of platinum-based chemotherapy (containing etoposide, vinblastine, vinorelbine, a taxane [paclitaxel or docetaxel], or pemetrexed) concurrently with definitive radiation therapy (54 to 66 Gy), in which the mean dose to the lung was less than 20 Gy, the V20 (the volume of lung parenchyma that received 20 Gy or more) was less than 35%, or both."

Immunotherapy

14-day cycle for up to 26 cycles (1 year)

References

  1. PACIFIC: Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. Epub 2017 Sep 8. link to original article contains dosing details in manuscript PubMed NCT02125461
    1. Update: Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. Epub 2018 Sep 25. link to original article PubMed
    2. Update: Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Özgüroğlu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. Epub 2019 Oct 14. link to original article link to PMC article PubMed
    3. Update: Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Özgüroğlu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. Epub 2021 Jan 19. link to original article PubMed
    4. Update: Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. Epub 2022 Feb 2. link to original article link to PMC article PubMed
  2. BGB-A317-A1217-301: NCT04866017
  3. CheckMate 73L: NCT04026412
  4. KEYLYNK-012: NCT04380636
  5. PACIFIC-8: NCT05211895
  6. PACIFIC-9: NCT05221840
  7. SKYSCRAPER-03: NCT04513925

Sugemalimab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Zhou et al. 2022 (GEMSTONE-301) 2018-2020 Phase 3 (E-esc) Placebo Superior PFS
Median PFS: 9 vs 5.8 mo
(HR 0.64, 95% CI 0.48-0.85)

Preceding treatment

  • Concurrent or sequential chemoradiotherapy

Immunotherapy

21-day cycle for up to 35 cycles (2 years)

References

  1. GEMSTONE-301: Zhou Q, Chen M, Jiang O, Pan Y, Hu D, Lin Q, Wu G, Cui J, Chang J, Cheng Y, Huang C, Liu A, Yang N, Gong Y, Zhu C, Ma Z, Fang J, Chen G, Zhao J, Shi A, Lin Y, Li G, Liu Y, Wang D, Wu R, Xu X, Shi J, Liu Z, Cui N, Wang J, Wang Q, Zhang R, Yang J, Wu YL. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-219. Epub 2022 Jan 14. link to original article contains dosing details in abstract PubMed NCT03728556

Advanced or metastatic disease, first-line

Atezolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (SKYSCRAPER-01) 2020-ongoing Phase 3 (C) Atezolizumab & Tiragolumab Awaiting results

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm, in this context.

Immunotherapy

21-day cycles

References

  1. SKYSCRAPER-01: NCT04294810

Carboplatin & Docetaxel

DCb: Docetaxel & Carboplatin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fossella et al. 2003 (TAX 326) 1998-2000 Phase 3 (E-RT-switch-ic) 1. Cisplatin & Docetaxel Not reported
2. Cisplatin & Vinorelbine Did not meet primary endpoint of OS
Booton et al. 2006 (BTOG1) 2001-2002 Phase 3 (E-switch-ic) 1. MIC
2. MVP 		Did not meet primary endpoint of OS
Groen et al. 2011 (NVALT-4) 2003-2007 Phase 3 (C) DCb & Celecoxib Did not meet primary endpoint of OS
Lynch et al. 2010 (BMS099) 2005-2006 Phase 3 (C) DCb & Cetuximab Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for up to 5 cycles (NVALT-4), 6 cycles (BMS099), or indefinitely

References

  1. TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains dosing details in abstract PubMed
  2. BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed
  3. BMS099: Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. link to original article contains dosing details in abstract PubMed NCT00112294
  4. NVALT-4: Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, Dalesio O, Biesma B, Smit HJ, Termeer A, Hiltermann TJ, van den Borne BE, Schramel FM. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol. 2011 Nov 10;29(32):4320-6. Epub 2011 Oct 11. link to original article PubMed NTR1703

Carboplatin & Etoposide (CE)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Klastersky et al. 1990 (EORTC 07861) 1987-1989 Phase 3 (E-switch-ic) Cisplatin & Etoposide Might have inferior ORR

Chemotherapy

3- to 4-week cycles

References

  1. EORTC 07861: Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. link to original article contains dosing details in manuscript PubMed

Carboplatin & Gemcitabine (GCb)

GC: Gemcitabine & Carboplatin
GCa: Gemcitabine & Carboplatin
GCb: Gemcitabine & Carboplatin

Regimen variant #1, 4/1000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Helbekkmo et al. 2007 2003-2004 Phase 3 (E-switch-ic) VCb Did not meet primary endpoint of OS

Note: AUC was calculated using the Chatelut formula.

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #2, 5/1000 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Grønberg et al. 2009 2005-2006 Phase 3 (C) Carboplatin & Pemetrexed Did not meet primary endpoint of HRQoL

Chemotherapy

21-day cycle for up to 4 cycles


Regimen variant #3, 5/1000 q4wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Danson et al. 2003 1997-2001 Phase 3 (E-switch-ic) 1. MIC
2. MVP 		Did not meet primary endpoint of OS

Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.

Chemotherapy

28-day cycle for 4 cycles


Regimen variant #4, 5/1200

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Zatloukal et al. 2003 1999-2001 Phase 3 (E-switch-ic) Cisplatin & Gemcitabine Did not meet primary endpoint of grade 3/4 toxicity
Rudd et al. 2005 1999-2001 Phase 3 (E-switch-ic) MIC Superior OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #5, 5/1250 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Sederholm et al. 2005 1998-2001 Phase 3 (C) Gemcitabine Seems to have superior OS
Bepler et al. 2013 (MCC-15005) 2007-2010 Phase 3 (C) ERCC1 and RRM1 expression-based chemotherapy Did not meet primary endpoint of PFS6
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL

Chemotherapy

21-day cycle for 4 to 6 cycles


Regimen variant #6, 5/1250 q4wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wu et al. 2013 (FASTACT-2) 2009-2010 Phase 3 (C) Carboplatin & Gemcitabine/Erlotinib Seems to have inferior OS

Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.

Chemotherapy

28-day cycle for 4 cycles


Regimen variant #7, 6/1000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kosmidis et al. 2007 2000-2004 Phase 3 (C) Gemcitabine & Paclitaxel Did not meet primary endpoint of OS

Chemotherapy

21-day cycles


Regimen variant #8, 6/1250 ("GCb6")

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Ferry et al. 2017 (BTOG2) 2005-2009 Phase 3 (E-switch-ic) 1. GC; GC50 Seems to have superior OS
2. GC; GC80 Non-inferior OS
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL

Chemotherapy

21-day cycle for 4 to 6 cycles


Regimen variant #9, 300/1000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Grigorescu et al. 2002 1997-2000 Phase 3 (E-switch-ic) Cisplatin & Vinblastine Superior OS

Chemotherapy

21-day cycles

References

  1. Grigorescu AC, Draghici IN, Nitipir C, Gutulescu N, Corlan E. Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial. Lung Cancer. 2002 Jul;37(1):9-14. link to original article contains dosing details in abstract PubMed
  2. Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article contains dosing details in abstract PubMed
  3. Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. link to original article contains dosing details in abstract PubMed
  4. Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, Hatton M, Johnson PW, Martin WM, Rankin EM, James LE, Gregory WM, Qian W, Lee SM; London Lung Cancer Group. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol. 2005 Jan 1;23(1):142-53. link to original article contains dosing details in abstract PubMed
  5. Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR; Swedish Lung Cancer Study Group. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article contains dosing details in manuscript PubMed
  6. Helbekkmo N, Sundstrøm SH, Aasebø U, Brunsvig PF, von Plessen C, Hjelde HH, Garpestad OK, Bailey A, Bremnes RM; Norwegian Lung Cancer Study Group. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer. 2007 Aug 6;97(3):283-9. Epub 2007 Jun 26. link to original article link to PMC article contains dosing details in manuscript PubMed
  7. Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. link to original article contains dosing details in abstract PubMed
  8. Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article contains dosing details in manuscript PubMed
  9. ALPHA A1-99002L: Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. link to original article contains dosing details in abstract PubMed NCT00054392
  10. MCC-15005: Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. Epub 2013 May 20. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00499109
  11. FASTACT-2: Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. link to original article contains dosing details in abstract PubMed NCT00883779
  12. NITRO: Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. link to original article PubMed ACTRN12608000588392
  13. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
  14. BTOG2: Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K; British Thoracic Oncology Group. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. link to original article contains dosing details in manuscript PubMed NCT00112710

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin
TC: Taxol (Paclitaxel) & Carboplatin

Regimen variant #1, 5/200

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL
Rizvi et al. 2020 (MYSTIC) 2015-2016 Phase 3 (C) Durvalumab Might have inferior OS
Durvalumab & Tremelimumab Did not meet primary endpoints of PFS/OS

Chemotherapy

21-day cycle for 4 to 6 cycles

Subsequent treatment

  • KEYNOTE-024: Patients with nonsquamous histology could optionally proceed to pemetrexed switch maintenance

Regimen variant #2, 6/175

Study Years of enrollment Evidence Comparator Comparative Efficacy
Stathopoulos et al. 2004 2000-2003 Phase 3 (C) Paclitaxel & Vinorelbine Did not meet primary endpoints of ORR/OS
Lynch et al. 2012 (CA184-041) 2008-2009 Randomized Phase 2 (C) CP & Ipilimumab Seems to have inferior PFS

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles


Regimen variant #3, 6/200

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Socinski et al. 2002 1998-2000 Phase 3 (E-de-esc) CP; indefinite Did not meet primary endpoint of OS Did not meet primary endpoint of QoL
Kosmidis et al. 2002 1998-2000 Phase 3 (E-switch-ic) Gemcitabine & Paclitaxel Did not meet primary endpoint of OS
Rosell et al. 2002 1996-1997 Phase 3 (E-switch-ic) Cisplatin & Paclitaxel Seems to have inferior OS
Johnson et al. 2004 NR Randomized Phase 2 (C) PacCBev Seems to have inferior TTP
Paccagnella et al. 2006 1998-2004 Phase 2/3 (C) PCG Seems to have inferior OS
Leighl et al. 2005 (NCIC-CTG BR.18) 2000-2002 Phase 3 (C) CP & BMS-275291 Did not meet primary endpoint of OS Less toxic
Ohe et al. 2006 (FACS) 2000-2002 Phase 3 (E-switch-ic) 1. Cisplatin & Gemcitabine Inconclusive whether non-inferior OS
2. Cisplatin & Irinotecan Inconclusive whether non-inferior OS
3. Cisplatin & Vinorelbine Inconclusive whether non-inferior OS
Herbst et al. 2005 (TRIBUTE) 2001-2002 Phase 3 (C) CP & Erlotinib Did not meet primary endpoint of OS
Schuette et al. 2006 NR Phase 3 (C) CP; weekly Seems to have non-inferior ORR Mixed toxicity
Blumenschein et al. 2008 (SPIRIT II) 2002-NR Phase 3 (C) CP & Bexarotene Did not meet primary endpoint of OS
Hirsh et al. 2011 (A8501001) 2005-2007 Phase 3 (C) CP & Agatolimod Did not meet primary endpoint of OS
Scagliotti et al. 2010 (ESCAPE) 2006-2007 Phase 3 (C) CP & Sorafenib Did not meet primary endpoint of OS
Okamoto et al. 2010 (LETS) 2006-2008 Phase 3 (C) Carboplatin & S-1 Non-inferior OS
Socinski et al. 2012 (CA031) 2007-2009 Phase 3 (C) Carboplatin & nab-Paclitaxel Inferior ORR
Lara et al. 2011 (ATTRACT-1) 2008-2009 Phase 3 (C) CP & Vadimezan Did not meet primary endpoint of OS
Langer et al. 2014 (A4021016) 2008-2009 Phase 3 (C) CP & Figitumumab Might have superior OS
Laurie et al. 2013 (NCIC-CTG BR.29) 2008-2011 Phase 3 (C) CP & Cediranib Did not meet primary endpoint of OS Less toxic
Herbst et al. 2017 (SWOG S0819) 2009-2014 Phase 3 (C) CP & Cetuximab Did not meet primary endpoints of PFS/OS
Ramalingam et al. 2016 (M10-898) 2012-2013 Randomized Phase 2 (C) CP & Veliparib Did not meet primary endpoint of PFS
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL
Rizvi et al. 2020 (MYSTIC) 2015-2016 Phase 3 (C) Durvalumab Might have inferior OS
Durvalumab & Tremelimumab Did not meet primary endpoints of PFS/OS

Note: Patients in TRIBUTE received a maximum of 6 cycles. Patients in SWOG S0819 were EGFR FISH positive.

Chemotherapy

21-day cycle for 3 or more cycles

Subsequent treatment

  • Socinski et al. 2002, upon progression: Paclitaxel
  • KEYNOTE-024: Patients with nonsquamous histology could optionally proceed, after 4 to 6 cycles, to pemetrexed switch maintenance

Regimen variant #4, 6/225

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kelly et al. 2001 (SWOG 9509) 1996-1998 Phase 3 (E-switch-ic) Cisplatin & Vinorelbine Did not meet primary endpoint of OS
Schiller et al. 2002 (ECOG E1594) 1996-1999 Phase 3 (E-switch-ic) 1. Cisplatin & Docetaxel Did not meet primary endpoint of OS
2. Cisplatin & Gemcitabine Did not meet primary endpoint of OS
3. Cisplatin & Paclitaxel Did not meet primary endpoint of OS
Lilenbaum et al. 2005 (CALGB 9730) 1997-2000 Phase 3 (E-esc) Paclitaxel Superior FFS
Herbst et al. 2004 (INTACT 2) 2000-2001 Phase 3 (C) CP & Gefitinib Did not meet primary endpoint of OS
Williamson et al. 2005 (SWOG S0003) 2000-2002 Phase 3 (C) CP & Tirapazamine Did not meet primary endpoint of OS
Belani et al. 2008 (BMS TAX/MEN.12) 2000-2004 Phase 3 (C) CP; weekly paclitaxel Did not meet primary endpoint of OS
Treat et al. 2009 (ALPHA A1-99002L) 2000-2005 Phase 3 (C) 1. Carboplatin & Gemcitabine
2. Gemcitabine & Paclitaxel 		Did not meet primary endpoint of OS
Kubota et al. 2008 (JMTO LC00-03) 2001-2005 Phase 3 (C) Gemcitabine & Vinorelbine, then Docetaxel Did not meet primary endpoint of OS
Median OS: 14.1 vs 13.6 mo
Weissman et al. 2011 (SR96669) 2004-2005 (T) Phase 3 (C) GemOx Did not meet primary endpoint of PFS
Median PFS: 4.7 vs 4.4 mo
Lynch et al. 2010 (BMS099) 2005-2006 (C) Phase 3 (C) CP & Cetuximab Did not meet primary endpoint of PFS
Median PFS: 4.2 vs 4.4 mo
(HR 1.11, 95% CI 0.94-1.31)

Chemotherapy

21-day cycle for up to 4 cycles (BMS TAX/MEN.12), 6 cycles (SR96669), 10 cycles (SWOG 9509), or indefinitely (ECOG E1594)

Subsequent treatment

References

  1. SWOG 9509: Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. link to original article contains dosing details in manuscript PubMed
  2. ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains dosing details in abstract PubMed
  3. Socinski MA, Schell MJ, Peterman A, Bakri K, Yates S, Gitten R, Unger P, Lee J, Lee JH, Tynan M, Moore M, Kies MS. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002 Mar 1;20(5):1335-43. link to original article contains dosing details in abstract PubMed
  4. Kosmidis P, Mylonakis N, Nicolaides C, Kalophonos C, Samantas E, Boukovinas J, Fountzilas G, Skarlos D, Economopoulos T, Tsavdaridis D, Papakostas P, Bacoyiannis C, Dimopoulos M. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2002 Sep 1;20(17):3578-85. link to original article contains dosing details in abstract PubMed
  5. Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. link to original article contains dosing details in abstract PubMed
  6. INTACT 2: Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol. 2004 Mar 1;22(5):785-94. link to original article contains dosing details in abstract PubMed
  7. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article PubMed
  8. Stathopoulos GP, Veslemes M, Georgatou N, Antoniou D, Giamboudakis P, Katis K, Tsavdaridis D, Rigatos SK, Dimitroulis I, Bastani S, Loukides S, Vergos K, Marossis K, Grigoratou T, Kalatzi E, Charalambatou M, Paspalli A, Michalopoulou P, Stoka M, Gerogianni A. Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial. Ann Oncol. 2004 Jul;15(7):1048-55. link to original article contains dosing details in abstract PubMed
  9. CALGB 9730: Lilenbaum RC, Herndon JE 2nd, List MA, Desch C, Watson DM, Miller AA, Graziano SL, Perry MC, Saville W, Chahinian P, Weeks JC, Holland JC, Green MR. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the Cancer and Leukemia Group B (study 9730). J Clin Oncol. 2005 Jan 1;23(1):190-6. link to original articlecontains dosing details in manuscript PubMed NCT00003117
  10. NCIC-CTG BR.18: Leighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, Santoro A, Betticher DC, Gatzemeier U, Jassem J, Crawford J, Tu D, Bezjak A, Humphrey JS, Voi M, Galbraith S, Hann K, Seymour L, Shepherd FA. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. link to original article contains dosing details in abstract PubMed NCT00006229
  11. TRIBUTE: Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5892-9. Epub 2005 Jul 25. link to original article contains dosing details in manuscript PubMed NCT00047736
  12. SWOG S0003: Williamson SK, Crowley JJ, Lara PN Jr, McCoy J, Lau DH, Tucker RW, Mills GM, Gandara DR; SWOG. Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003. J Clin Oncol. 2005 Dec 20;23(36):9097-104. link to original article contains dosing details in abstract PubMed NCT00006484
  13. Schuette W, Blankenburg T, Guschall W, Dittrich I, Schroeder M, Schweisfurth H, Chemaissani A, Schumann C, Dickgreber N, Appel T, Ukena D. Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Clin Lung Cancer. 2006 Mar;7(5):338-43. link to original article contains dosing details in abstract PubMed
  14. Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. link to original article contains dosing details in manuscript PubMed
  15. FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article contains dosing details in manuscript PubMed
  16. BMS TAX/MEN.12: Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, Tester WJ. Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol. 2008 Jan 20;26(3):468-73. link to original article contains dosing details in abstract PubMed NCT00035152
  17. SPIRIT II: Blumenschein GR Jr, Khuri FR, von Pawel J, Gatzemeier U, Miller WH Jr, Jotte RM, Le Treut J, Sun SL, Zhang JK, Dziewanowska ZE, Negro-Vilar A. Phase III trial comparing carboplatin, paclitaxel, and bexarotene with carboplatin and paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT II. J Clin Oncol. 2008 Apr 10;26(11):1879-85. link to original article contains dosing details in manuscript PubMed NCT00050960
  18. JMTO LC00-03: Kubota K, Kawahara M, Ogawara M, Nishiwaki Y, Komuta K, Minato K, Fujita Y, Teramukai S, Fukushima M, Furuse K; Japan Multi-National Trial Organisation. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008 Dec;9(12):1135-42. Epub 2008 Nov 13. link to original article contains dosing details in abstract PubMed NCT00079287
  19. ALPHA A1-99002L: Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. link to original article contains dosing details in abstract PubMed NCT00054392
  20. BMS099: Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. link to original article contains dosing details in abstract PubMed NCT00112294
  21. ESCAPE: Scagliotti G, Novello S, von Pawel J, Reck M, Rodrigues Pereira J, Thomas M, Abrão Miziara JE, Balint B, De Marinis F, Keller A, Arén O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, Dimatteo S, Hanna N. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010 Apr 10;28(11):1835-42. Epub 2010 Mar 8. link to original article contains dosing details in abstract PubMed NCT00300885
    1. Dataset: Project Data Sphere
  22. LETS: Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K; West Japan Oncology Group. Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a West Japan Oncology Group study. J Clin Oncol. 2010 Dec 20;28(36):5240-6. Epub 2010 Nov 15. link to original article contains dosing details in manuscript PubMed UMIN000000503
  23. SR96669: Weissman CH, Reynolds CH, Neubauer MA, Pritchard S, Kobina S, Asmar L. A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011 Feb;6(2):358-64. link to original article contains dosing details in abstract PubMed NCT00087802
  24. A8501001: Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE, Szczesna A, Reiterer P, Saleh M, Arrieta O, Bajetta E, Webb RT, Raats J, Benner RJ, Fowst C, Meech SJ, Readett D, Schiller JH. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2011 Jul 1;29(19):2667-74. Epub 2011 May 31. link to original article contains dosing details in manuscript PubMed NCT00254891
  25. ATTRACT-1: Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, Losonczy G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol. 2011 Aug 1;29(22):2965-71. Epub 2011 Jun 27. link to original article contains dosing details in manuscript PubMed NCT00662597
  26. CA184-041: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00527735
  27. CA031: Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00540514
    1. Dataset: Project Data Sphere
  28. NCIC-CTG BR.29: Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer. 2014 Mar;50(4):706-12. Epub 2013 Dec 17. link to original article contains dosing details in abstract PubMed NCT00795340
  29. A4021016: Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2. link to original article link to PMC article PubMed NCT00596830
  30. NITRO: Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. link to original article PubMed ACTRN12608000588392
  31. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
  32. M10-898: Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E, Urban L, Orlov S, Barlesi F, Kio E, Keiholz U, Qin Q, Qian J, Nickner C, Dziubinski J, Xiong H, Ansell P, McKee M, Giranda V, Gorbunova V. Randomized, placebo-controlled, phase II study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer. Clin Cancer Res. 2017 Apr 15;23(8):1937-1944. Epub 2016 Oct 10. link to original article contains dosing details in abstract PubMed NCT01560104
  33. SWOG S0819: Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. link to original article contains dosing details in abstract PubMed NCT00946712
  34. MYSTIC: Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):661-674. link to original article contains dosing details in supplement link to PMC article PubMed NCT02453282
  35. ARC-10: NCT04736173

Carboplatin & nab-Paclitaxel

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Socinski et al. 2012 (CA031) 2007-2009 Phase 3 (E-RT-switch-ic) Carboplatin & Paclitaxel Superior ORR

Chemotherapy

21-day cycle for 6 cycles; treatment could continue at physician's discretion if there was no progressive disease or unacceptable toxicity

References

  1. CA031: Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00540514
    1. Dataset: Project Data Sphere

Carboplatin & Paclitaxel (CP) & Bevacizumab

PacCBev: Paclitaxel, Carboplatin, Bevacizumab
B+CP: Bevacizumab, Carboplatin, Paclitaxel
BCP: Bevacizumab, Carboplatin, Paclitaxel

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Johnson et al. 2004 NR Randomized Phase 2 (E-esc) Carboplatin & Paclitaxel Seems to have superior TTP
Herbst et al. 2017 (SWOG S0819) 2009-2014 Phase 3 (C) Carboplatin, Paclitaxel, Bevacizumab, Cetuximab Did not meet primary endpoints of PFS/OS

Biomarker eligibility criteria

  • SWOG S0819: EGFR FISH positive

Chemotherapy

  • Carboplatin (Paraplatin) AUC 6 IV over 15 to 30 minutes once on day 1, given second, starting 60 minutes after the completion of paclitaxel
  • Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first

Targeted therapy

  • Bevacizumab (Avastin) 15 mg/kg IV once on day 1, given third, starting 60 minutes after the completion of carboplatin
    • Infusion time per Johnson, et al. 2004 was over 90 minutes for cycle 1; if tolerated, given over 30 to 60 minutes for cycles 2 and later

21-day cycle for up to 6 cycles

References

  1. Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article PubMed
  2. SWOG S0819: Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. link to original article contains dosing details in abstract PubMed NCT00946712

Carboplatin & Paclitaxel (CP) & Ipilimumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lynch et al. 2012 (CA184-041) 2008-2009 Randomized Phase 2 (E-esc) Carboplatin & Paclitaxel Seems to have superior PFS

Note: this is the "phased" approach to this regimen.

Chemotherapy

Immunotherapy

Supportive therapy

21-day cycle for up to 6 cycles

Subsequent treatment

References

  1. CA184-041: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00527735

Carboplatin & Pemetrexed

CP: Carboplatin & Pemetrexed
Carbo-Pem: Carboplatin & Pemetrexed

Example orders

Regimen variant #1, 5/500 x 6

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles

Subsequent treatment


Regimen variant #2, 6/500 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Grønberg et al. 2009 2005-2006 Phase 3 (E-switch-ic) Carboplatin & Gemcitabine Did not meet primary endpoint of HRQoL

Chemotherapy

Supportive therapy

21-day cycle for up to 4 cycles


Regimen variant #3, 6/500 x 6

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles

Subsequent treatment

References

  1. Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article contains dosing details in abstract PubMed
  2. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed

Carboplatin & Vinorelbine

VC: Vinorelbine & Carboplatin

Regimen variant #1, IV vinorelbine

Study Years of enrollment Evidence Comparator Comparative Efficacy
Tan et al. 2005 (GLOB 2) 2000-2002 Phase 3 (C) Gemcitabine & Vinorelbine Did not meet primary endpoint of ORR

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #2, PO vinorelbine

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fløtten et al. 2012 2007-2009 Phase 3 (C) Gemcitabine & Vinorelbine Did not meet primary endpoint of OS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

21-day cycle for 3 cycles

References

  1. GLOB 2: Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. link to original article contains dosing details in abstract PubMed
  2. Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. link to original article link to PMC article contains dosing details in abstract PubMed NCT00737867

Cemiplimab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sezer et al. 2021 (EMPOWER-Lung 1) 2017-2020 Phase 3 (E-RT-switch-ooc) 1. Carboplatin & Gemcitabine
2. Carboplatin & Paclitaxel
3. Carboplatin & Pemetrexed
4. Cisplatin & Gemcitabine
5. Cisplatin & Paclitaxel
6. Cisplatin & Pemetrexed 		Superior OS
Median OS: NYR vs 14.2 mo
(HR 0.57, 95% CI 0.42-0.77)

Note: some of the comparator platinum doublets appear to be histology-specific, but this is not specified in the manuscript or protocol. We have reached out to the authors for clarification. Per Sanofi, "it was strongly recommended that patients with squamous NSCLC do not receive pemetrexed-containing regimens"; otherwise, no histology-specific guidance was provided to the investigator.

Biomarker eligibility criteria

  • PD-L1 expressed in at least 50% of tumor cells

Immunotherapy

21-day cycle for up to 36 cycles (2 years)

References

  1. EMPOWER-Lung 1: Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. link to original article contains dosing details in manuscript PubMed NCT03088540

Cisplatin & Docetaxel (DC)

DC: Docetaxel & Cisplatin
DP: Docetaxel & Platinol (Cisplatin)
Doc-Cis: Docetaxel & Cisplatin

Regimen variant #1, 50/75

Study Years of enrollment Evidence Comparator Comparative Efficacy
Berghmans et al. 2013 (ELCWP-01041) 2003-2009 Phase 3 (C) 1. GIP
2. IG 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycles


Regimen variant #2, 75/75

Study Years of enrollment Evidence Comparator Comparative Efficacy
Schiller et al. 2002 (ECOG E1594) 1996-1999 Phase 3 (E-switch-ic) 1. Carboplatin & Paclitaxel Did not meet primary endpoint of OS
2. Cisplatin & Gemcitabine Did not meet primary endpoint of OS
3. Cisplatin & Paclitaxel Did not meet primary endpoint of OS
Fossella et al. 2003 (TAX 326) 1998-2000 Phase 3 (E-RT-switch-ic) 1. Carboplatin & Docetaxel Not reported
2. Cisplatin & Vinorelbine Seems to have superior OS
Cobo et al. 2007 2001-2005 Phase 3 (C) ERCC1 mRNA-guided therapy Seems to have inferior ORR
Tan et al. 2009 (GLOB3) 2004-2006 Phase 3 (C) Cisplatin & Vinorelbine Did not meet primary endpoint of TTF

Chemotherapy

21-day cycle for up to 6 cycles (GLOB3) or indefinitely (E1594, TAX326)


Regimen variant #3, 80/60

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kubota et al. 2004 1998-2000 Phase 3 (E-switch-ic) Cisplatin & Vindesine Seems to have superior OS
Takeda et al. 2009 (WJTOG0203) 2003-2005 Phase 3 (C) Platinum doublet x 3, then Gefitinib Did not meet primary endpoint of OS
Kubota et al. 2015 (TCOG0701 CATS) 2007-2008 Phase 3 (C) Cisplatin & S-1 Non-inferior OS

Chemotherapy

21-day cycle for 3 to 6 cycles


Regimen variant #4, 80/100

Study Years of enrollment Evidence Comparator Comparative Efficacy
Georgoulias et al. 2001 1997-1999 Phase 3 (C) Docetaxel & Gemcitabine Did not meet primary endpoints of ORR/TTP
Georgoulias et al. 2003 NR Phase 3 (C) Docetaxel Did not meet primary endpoint of OS

Chemotherapy

21-day cycles

References

  1. Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, Palamidas P, Vlachonikolis I; Greek Oncology Cooperative Group (GOCG) for Lung Cancer. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet. 2001 May 12;357(9267):1478-84. link to original article PubMed
  2. ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains dosing details in abstract PubMed
  3. Georgoulias V, Pallis AG, Kourousis C, Alexopoulos A, Ardavanis A, Agelidou A, Agelidou M, Toumbis M, Tzannes S, Pavlakou G, Ziotopoulos P, Tzelepatiotis E, Samaras N; Hellenic Oncology Research Group. Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study. Clin Lung Cancer. 2003 Mar;4(5):288-93. link to original article PubMed
    1. Update: Georgoulias V, Ardavanis A, Agelidou A, Agelidou M, Chandrinos V, Tsaroucha E, Toumbis M, Kouroussis C, Syrigos K, Polyzos A, Samaras N, Papakotoulas P, Christofilakis C, Ziras N, Alegakis A. Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol. 2004 Jul 1;22(13):2602-9. link to original article contains dosing details in abstract PubMed
  4. TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains dosing details in abstract PubMed
  5. Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. link to original article contains dosing details in abstract PubMed
  6. Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, Viñolas N, Paz-Ares L, Lopez-Vivanco G, Muñoz MA, Felip E, Alberola V, Camps C, Domine M, Sanchez JJ, Sanchez-Ronco M, Danenberg K, Taron M, Gandara D, Rosell R. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007 Jul 1;25(19):2747-54. link to original article contains dosing details in manuscript PubMed
  7. Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article contains dosing details in manuscript PubMed
  8. GLOB3: Tan EH, Rolski J, Grodzki T, Schneider CP, Gatzemeier U, Zatloukal P, Aitini E, Carteni G, Riska H, Tsai YH, Abratt R. Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and iv vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2009 Jul;20(7):1249-56. Epub 2009 Mar 10. link to original article contains dosing details in abstract PubMed
  9. WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article contains dosing details in manuscript PubMed NCT00144066
  10. ELCWP-01041: Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. link to original article contains dosing details in manuscript PubMed NCT00622349
  11. TCOG0701 CATS: Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S; Tokyo Cooperative Oncology Group. A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol. 2015 Jul;26(7):1401-8. Epub 2015 Apr 23. link to original article link to PMC article contains dosing details in abstract PubMed UMIN000000608

Cisplatin & Etoposide (EP)

PE: Platinol (Cisplatin) & Etoposide
EC: Etoposide & Cisplatin

Regimen variant #1, 60/360

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ruckdeschel et al. 1986 (ECOG E1581) 1981-1983 Phase 3 (E-switch-ic) 1. CAMP
2. Cisplatin & Vindesine
3. MVP 		Did not meet primary endpoint

Note: this is an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.

Chemotherapy

21-day cycles


Regimen variant #2, 75/300

Study Years of enrollment Evidence Comparator Comparative Efficacy
Bonomi et al. 2000 (ECOG E5592) 1993-1994 Phase 3 (C) Cisplatin & Paclitaxel Seems to have inferior OS
Belani et al. 2005 1995-1996 Phase 3 (C) Carboplatin & Paclitaxel Might have superior OS

Chemotherapy

21-day cycles


Regimen variant #3, 100/300

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cardenal et al. 1999 1995-1996 Phase 3 (C) Cisplatin & Gemcitabine Inferior TTP

Chemotherapy

21-day cycles


Regimen variant #4, 105/600

Study Years of enrollment Evidence Comparator Comparative Efficacy
Font et al. 1999 1993-1995 Phase 3 (C) PE; dose-dense Did not meet primary endpoint of ORR

Chemotherapy

28-day cycles


Regimen variant #5, 120/300

Study Years of enrollment Evidence Comparator Comparative Efficacy
Klastersky et al. 1990 (EORTC 07861) 1987-1989 Phase 3 (C) Carboplatin & Etoposide Might have superior ORR
Comella et al. 1996 1993-1995 Phase 3 (C) Carboplatin, Cisplatin, Etoposide, Vinorelbine Did not meet primary endpoint of ORR

Chemotherapy

3- to 4-week cycles

References

  1. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article contains dosing details in manuscript PubMed
  2. EORTC 07861: Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. link to original article contains dosing details in manuscript PubMed
  3. Comella P, Frasci G, De Cataldis G, Panza N, Cioffi R, Curcio C, Belli M, Bianco A, Ianniello G, Maiorino L, Della Vittoria M, Perchard J, Comella G; Gruppo Oncologico Campano. Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Br J Cancer. 1996 Dec;74(11):1805-11. link to original article link to PMC article contains dosing details in abstract PubMed
  4. Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. link to original article contains dosing details in abstract PubMed
  5. Font A, Moyano AJ, Puerto JM, Tres A, Garcia-Giron C, Barneto I, Anton A, Sanchez JJ, Salvador A, Rosell R; Spanish Lung Cancer Group. Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group. Cancer. 1999 Feb 15;85(4):855-63. link to original article PubMed
  6. ECOG E5592: Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. link to original article contains dosing details in manuscript PubMed
  7. Belani CP, Lee JS, Socinski MA, Robert F, Waterhouse D, Rowland K, Ansari R, Lilenbaum R, Natale RB. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol. 2005 Jul;16(7):1069-75. Epub 2005 Apr 28. link to original article contains dosing details in abstract PubMed

Cisplatin & Gemcitabine (GC)

GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)

Regimen variant #1, 70/1000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Park et al. 2007 2002-2004 Phase 3 (E-de-esc) GC; 6 cycles Non-inferior OS

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #2, 75/1250 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Bissett et al. 2005 (AG-3340-017) 1999-2001 Phase 3 (C) GC & Prinomastat Did not meet primary endpoint of OS
Novello et al. 2007 2001-2004 Phase 3 (C) GC x 2, then gemcitabine x 3 Inconclusive whether non-inferior OS
Manegold et al. 2011 2005-2007 Phase 3 (C) GC & PF-3512676 Did not meet primary endpoint of OS
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (C) Pembrolizumab Inferior OS Inferior HRQoL

Note: Patients in Novello et al. 2007 received 5 cycles. Patients in KEYNOTE-024 received 4 to 6 cycles.

Chemotherapy

21-day cycle for up to 6 cycles (see note)


Regimen variant #3, 75/1250 q4wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wu et al. 2013 (FASTACT-2) 2009-2010 Phase 3 (C) GC/Erlotinib Seems to have superior OS

Note: this cohort was enriched for EGFR mutations and only those patients with an activating EGFR gene mutation were noted to have a treatment benefit in favor of the experimental arm.

Chemotherapy

28-day cycle for 4 cycles


Regimen variant #4, 80/1000

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ohe et al. 2006 (FACS) 2000-2002 Phase 3 (E-switch-ic) 1. Carboplatin & Paclitaxel Inconclusive whether non-inferior OS
2. Cisplatin & Irinotecan Inconclusive whether non-inferior OS
3. Cisplatin & Vinorelbine Inconclusive whether non-inferior OS
Takeda et al. 2009 (WJTOG0203) 2003-2005 Phase 3 (C) Platinum doublet x 3, then Gefitinib Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for 6 cycles (WJTOG0203) or indefinitely (FACS)


Regimen variant #5, 80/1125

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wachters et al. 2003 1998-2002 Phase 3 (C) Epirubicin & Gemcitabine Did not meet primary endpoint of PFS

Chemotherapy

21-day cycle for up to 5 cycles


Regimen variant #6, 80/1200 x 6

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gridelli et al. 2003 (NCIC-CTG BR.14) 1998-2001 Phase 3 (C) Gemcitabine & Vinorelbine Might have superior OS
Gridelli et al. 2007 (GECO) 2003-2005 Phase 3 (C) 1. GC & Rofecoxib
2. Cisplatin & Gemcitabine; PCI gemcitabine
3. GC & Rofecoxib; PCI gemcitabine 		Did not meet primary endpoint of OS
Gridelli et al. 2012 (TORCH) 2006-2009 Phase 3 (C) Erlotinib Seems to have superior OS
Median OS: 11.6 vs 8.7 mo
(HR 0.81, 95% CI 0.68-0.96)

Chemotherapy

21-day cycle for up to 6 cycles

Subsequent treatment


Regimen variant #7, 80/1250 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ferry et al. 2017 (BTOG2) 2005-2009 Phase 3 (E-esc) 1. GC; GC50 Seems to have superior OS
2. GCb6 Non-inferior OS
Pérol et al. 2012 (IFCT-GFPC 0502) 2006-2009 Non-randomized portion of phase 3 RCT

Chemotherapy

21-day cycle for 4 cycles

Subsequent treatment


Regimen variant #8, 80/1250 x 6

Study Years of enrollment Evidence Comparator Comparative Efficacy
Giaccone et al. 2004 (INTACT 1) 2000-2001 Phase 3 (C) GC & Gefitinib Did not meet primary endpoint of OS
Gatzemeier et al. 2007 (TALENT) 2001-2002 Phase 3 (C) GC & Erlotinib Did not meet primary endpoint of OS
Boni et al. 2012 (FAST) 2001-2006 Phase 3 (C) 1. GIN
2. GN 		Seems to have superior OS
3. GIP Did not meet primary endpoint of OS
Paz-Ares et al. 2006 2002-2004 Phase 3 (C) GC & Aprinocarsen Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #9, 100/1000 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ridolfi et al. 2011 2000-2004 Phase 3 (C) GC & LD IL-2 Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #10, 100/1000 q4wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Crinò et al. 1999 1995-1997 Phase 3 (E-switch-ic) MIC Seems to have superior ORR
Sandler et al. 2000 1995-1997 Phase 3 (E-RT-esc) Cisplatin Superior OS
Schiller et al. 2002 (ECOG E1594) 1996-1999 Phase 3 (E-switch-ic) 1. Carboplatin & Paclitaxel Did not meet primary endpoint of OS
2. Cisplatin & Docetaxel Did not meet primary endpoint of OS
3. Cisplatin & Paclitaxel Superior PFS
Scagliotti et al. 2008 (JMDB) 2004-2005 Phase 3 (C) Cisplatin & Pemetrexed Seems to have non-inferior OS

Chemotherapy

28-day cycles


Regimen variant #11, 100/1250

Study Years of enrollment Evidence Comparator Comparative Efficacy
Cardenal et al. 1999 1995-1996 Phase 3 (E-RT-switch-ic) Cisplatin & Etoposide Superior TTP
Alberola et al. 2003 1998-2000 Phase 3 (C) 1. CGV
2. GV-VI 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for 6 cycles (Alberola et al. 2003) or indefinitely (Cardenal et al. 1999)


Regimen variant #12, 100/1400

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gebbia et al. 2003 NR Phase 3 (E-switch-ic) Cisplatin & Vinorelbine Did not meet primary endpoint of OS

Chemotherapy

28-day cycles

References

  1. Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. link to original article contains dosing details in abstract PubMed
  2. Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. link to original article contains dosing details in abstract PubMed
  3. Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122-30. link to original article contains dosing details in abstract PubMed
  4. ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains dosing details in abstract PubMed
  5. Gebbia V, Galetta D, Caruso M, Verderame F, Pezzella G, Valdesi M, Borsellino N, Pandolfo G, Durini E, Rinaldi M, Loizzi M, Gebbia N, Valenza R, Tirrito ML, Varvara F, Colucci G; Gruppo Ocologico Italia Meridionale. Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale. Lung Cancer. 2003 Feb;39(2):179-89. link to original article contains dosing details in abstract PubMed
  6. NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00004100
  7. Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, Ruiz-Casado A, Azagra P, Jiménez U, González-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Peñas R, Felip E, López-Vivanco G; Spanish Lung Cancer Group. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol. 2003 Sep 1;21(17):3207-13. link to original article contains dosing details in abstract PubMed
  8. Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. link to original article contains dosing details in abstract PubMed
  9. Wachters FM, Van Putten JW, Kramer H, Erjavec Z, Eppinga P, Strijbos JH, de Leede GP, Boezen HM, de Vries EG, Groen HJ. First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial. Br J Cancer. 2003 Oct 6;89(7):1192-9. link to original article link to PMC article contains dosing details in abstract PubMed
  10. INTACT 1: Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol. 2004 Mar 1;22(5):777-84. link to original article contains dosing details in abstract PubMed
  11. AG-3340-017: Bissett D, O'Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, Mercier R, Mazabel E, Penning C, Zhang MH, Collier MA, Shepherd FA. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol. 2005 Feb 1;23(4):842-9. link to original article contains dosing details in abstract PubMed NCT00004199
  12. Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, Chang GC, John WJ, Peterson PM, Obasaju CK, Lahn M, Gandara DR. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2006 Mar 20;24(9):1428-34. link to original article contains dosing details in abstract PubMed
  13. FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article contains dosing details in manuscript PubMed
  14. Novello S, Bruzzi P, Barone C, Buosi R, Masotti A, Michetti G, Fioretti M, Barbera S, Spatafora M, Garetto L, Mazzanti P, Dongiovanni V, Selvaggi G, Crinò L, Scagliotti GV. Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone. Ann Oncol. 2007 May;18(5):903-8. Epub 2007 Mar 9. link to original article contains dosing details in abstract PubMed
  15. TALENT: Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007 Apr 20;25(12):1545-52. link to original article contains dosing details in abstract PubMed
  16. GECO: Gridelli C, Gallo C, Ceribelli A, Gebbia V, Gamucci T, Ciardiello F, Carozza F, Favaretto A, Daniele B, Galetta D, Barbera S, Rosetti F, Rossi A, Maione P, Cognetti F, Testa A, Di Maio M, Morabito A, Perrone F; GECO investigators. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol. 2007 Jun;8(6):500-12. link to original article contains dosing details in abstract PubMed NCT00385606
  17. Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article contains dosing details in manuscript PubMed
  18. JMDB: Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article contains dosing details in abstract PubMed NCT00087711
  19. WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article contains dosing details in manuscript PubMed NCT00144066
  20. Manegold C, van Zandwijk N, Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M, Serwatowski P, Krzakowski M, Jassem J, Tan EH, Benner RJ, Ingrosso A, Meech SJ, Readett D, Thatcher N. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2012 Jan;23(1):72-7. Epub 2011 Apr 4. link to original article contains dosing details in abstract PubMed
  21. Ridolfi L, Bertetto O, Santo A, Naglieri E, Lopez M, Recchia F, Lissoni P, Galliano M, Testore F, Porta C, Maglie M, Dall'agata M, Fumagalli L, Ridolfi R. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial. Int J Oncol. 2011 Oct;39(4):1011-7. Epub 2011 Jun 24. link to original article contains dosing details in abstract PubMed
  22. FAST: Boni C, Tiseo M, Boni L, Baldini E, Recchia F, Barone C, Grossi F, Germano D, Matano E, Marini G, Labianca R, Di Costanzo F, Bagnulo A, Pennucci C, Caroti C, Mencoboni M, Zanelli F, Prochilo T, Cafferata MA, Ardizzoni A; Gruppo Oncologico Italiano di Ricerca Clinica. Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST). Br J Cancer. 2012 Feb 14;106(4):658-65. Epub 2012 Jan 12. link to original article link to PMC article contains dosing details in manuscript PubMed
  23. TORCH: Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012 Aug 20;30(24):3002-11. Epub 2012 Jul 9. link to original article contains dosing details in abstract PubMed NCT00349219
    1. HRQoL analysis: Di Maio M, Leighl NB, Gallo C, Feld R, Ciardiello F, Butts C, Maione P, Gebbia V, Morgillo F, Wierzbicki R, Favaretto A, Alam Y, Cinieri S, Siena S, Bianco R, Riccardi F, Spatafora M, Ravaioli A, Felletti R, Fregoni V, Genestreti G, Rossi A, Mancuso G, Fasano M, Morabito A, Tsao MS, Signoriello S, Perrone F, Gridelli C. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advancednon-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1830-1844. link to original article PubMed
  24. IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original articlecontains dosing details in manuscript PubMed NCT00300586
  25. FASTACT-2: Wu YL, Lee JS, Thongprasert S, Yu CJ, Zhang L, Ladrera G, Srimuninnimit V, Sriuranpong V, Sandoval-Tan J, Zhu Y, Liao M, Zhou C, Pan H, Lee V, Chen YM, Sun Y, Margono B, Fuerte F, Chang GC, Seetalarom K, Wang J, Cheng A, Syahruddin E, Qian X, Ho J, Kurnianda J, Liu HE, Jin K, Truman M, Bara I, Mok T. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial. Lancet Oncol. 2013 Jul;14(8):777-86. Epub 2013 Jun 17. link to original article contains dosing details in abstract PubMed NCT00883779
  26. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
  27. BTOG2: Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. link to original article contains dosing details in manuscript PubMed NCT00112710

Cisplatin & Gemcitabine (GC) & Cetuximab

Regimen

Study Years of enrollment Evidence
Butts et al. 2008 NR Randomized Phase 2 (E-esc)

Note: this was a non-comparative study.

Chemotherapy

Targeted therapy

  • Cetuximab (Erbitux) as follows:
    • Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once per day on days 8 & 15
    • Cycle 2 onwards: 250 mg/m2 IV once per day on days 1, 8, 15

21-day cycle for up to 6 cycles

References

  1. Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, Kreisman H, Graze P, Maher J, Ross HJ, Ellis PM, McNulty W, Kaplan E, Pautret V, Weber MR, Shepherd FA. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol. 2007 Dec 20;25(36):5777-84. Erratum in: J Clin Oncol. 2008 Jul 1;26(19): 3295. link to original article contains dosing details in manuscript PubMed

Cisplatin & Irinotecan (IC)

IP: Irinotecan & Platinol (Cisplatin)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Negoro et al. 2003 1995-1998 Phase 3 (E-switch-ic) Cisplatin & Vindesine Did not meet primary endpoint of OS
Irinotecan Not reported
Ohe et al. 2006 (FACS) 2000-2002 Phase 3 (C) 1. Carboplatin & Paclitaxel Inconclusive whether non-inferior OS
2. Cisplatin & Gemcitabine Inconclusive whether non-inferior OS
3. Cisplatin & Vinorelbine Inconclusive whether non-inferior OS
Takeda et al. 2009 (WJTOG0203) 2003-2005 Phase 3 (C) Platinum doublet x 3, then Gefitinib Did not meet primary endpoint of OS

Chemotherapy

28-day cycle for up to 6 cycles (WJTOG0203) or indefinitely (FACS)

References

  1. Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. link to original article link to PMC article contains dosing details in manuscript PubMed
  2. FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article contains dosing details in manuscript PubMed
  3. WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article contains dosing details in manuscript PubMed NCT00144066

Cisplatin & Paclitaxel

PC: Paclitaxel & Cisplatin

Regimen variant #1, 70/175 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy
Park et al. 2007 2002-2004 Phase 3 (E-de-esc) Cisplatin & Paclitaxel x 6 Non-inferior OS

Chemotherapy

21-day cycle for 4 cycles


Regimen variant #2, 70/175 x 6

Study Years of enrollment Evidence Comparator Comparative Efficacy
Park et al. 2007 2002-2004 Phase 3 (C) Cisplatin & Paclitaxel x 4 Non-inferior OS
Shi et al. 2020 (PM-03-2015) 2015-2018 Phase 3 (C) Cisplatin & Paclitaxel micellar Inferior PFS

Chemotherapy

21-day cycle for 6 cycles


Regimen variant #3, 75/135, q2wk

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Stathopoulos et al. 2010a 2006-2008 Phase 3 (C) Liposomal Cisplatin & Paclitaxel Did not meet secondary endpoints More toxic

Chemotherapy

14-day cycle for up to 9 cycles


Regimen variant #4, 75/135, q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Bonomi et al. 2000 (ECOG E5592) 1993-1994 Phase 3 (E-RT-switch-ic) Cisplatin & Etoposide Seems to have superior OS
Schiller et al. 2002 (ECOG E1594) 1996-1999 Phase 3 (C) 1. Carboplatin & Paclitaxel Did not meet primary endpoint of OS
2. Cisplatin & Docetaxel Did not meet primary endpoint of OS
3. Cisplatin & Gemcitabine Inferior PFS

Chemotherapy

21-day cycles


Regimen variant #5, 80/175

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gatzemeier et al. 2000 1995-1996 Phase 3 (E-esc) Cisplatin Seems to have superior TTP
Smit et al. 2003 (EORTC 08975) 1998-2000 Phase 3 (C) 1. Cisplatin & Gemcitabine
2. Gemcitabine & Paclitaxel 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #6, 80/200

Study Years of enrollment Evidence Comparator Comparative Efficacy
Rosell et al. 2002 1996-1997 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Seems to have superior OS

Chemotherapy

21-day cycles

References

  1. ECOG E5592: Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. link to original article contains dosing details in abstract PubMed
  2. Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. link to original article contains dosing details in abstract PubMed
  3. ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains dosing details in manuscript PubMed
  4. Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. link to original article contains dosing details in abstract PubMed
  5. EORTC 08975: Smit EF, van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, Smit H, Gaafar R, Biesma B, Manegold C, Neymark N, Giaccone G; EORTC Lung Cancer Group. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organisation for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol. 2003 Nov 1;21(21):3909-17. link to original article contains dosing details in abstract PubMed NCT00003589
  6. Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article contains dosing details in manuscript PubMed
  7. Stathopoulos GP, Antoniou D, Dimitroulis J, Michalopoulou P, Bastas A, Marosis K, Stathopoulos J, Provata A, Yiamboudakis P, Veldekis D, Lolis N, Georgatou N, Toubis M, Pappas Ch, Tsoukalas G. Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial. Ann Oncol. 2010 Nov;21(11):2227-32. Epub 2010 May 3. link to original article link to PMC article contains dosing details in manuscript PubMed
  8. PM-03-2015: Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, Wang X, Cao L, Shu Y, Wang H, Yang R, Li X, Chang J, Hu Y, Shen P, Hu Y, Guo Z, Tao M, Zhang Y, Liu X, Sun Q, Zhang X, Jiang Z, Zhao J, Chen F, Yu H, Zhang W, Sun J, Li D, Zhou J, Han B, Wu YL. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021 Jan;32(1):85-96. Epub 2020 Oct 29. link to original article contains dosing details in abstract PubMed NCT02667743

Cisplatin & Vinorelbine (CVb)

CVb: Cisplatin & Vinorelbine
CV: Cisplatin & Vinorelbine
NP: Navelbine (Vinorelbine) & Platinol (Cisplatin)
PV: Platinol (Cisplatin) & Vinorelbine
VC: Vinorelbine & Cisplatin

Regimen variant #1, 75/25

Study Years of enrollment Evidence Comparator Comparative Efficacy
Martoni et al. 2005 1998-2003 Phase 3 (E-switch-ic) Cisplatin & Gemcitabine Did not meet primary endpoint of ORR

Chemotherapy

21-day cycle for up to 6 cycles

Subsequent treatment


Regimen variant #2, 80/25

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ohe et al. 2006 (FACS) 2000-2002 Phase 3 (E-switch-ic) 1. Carboplatin & Paclitaxel Inconclusive whether non-inferior OS
2. Cisplatin & Gemcitabine Inconclusive whether non-inferior OS
3. Cisplatin & Irinotecan Inconclusive whether non-inferior OS
Takeda et al. 2009 (WJTOG0203) 2003-2005 Phase 3 (C) Platinum doublet x 3, then Gefitinib Did not meet primary endpoint of OS
Pirker et al. 2009 (FLEX) 2004-2006 Phase 3 (C) Cisplatin, Vinorelbine, Cetuximab Seems to have inferior OS

Chemotherapy

21-day cycle for up to 6 cycles (FLEX; WJTOG0203) or indefinitely (FACS)


Regimen variant #3, 80/30, 2 out of 3 weeks vinorelbine

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Gridelli et al. 2003 (NCIC-CTG BR.14) 1998-2001 Phase 3 (C) Gemcitabine & Vinorelbine Might have superior OS
Georgoulias et al. 2005 1999-2002 Phase 3 (C) Docetaxel & Gemcitabine Did not meet primary endpoint of OS
Gebbia et al. 2008 2003-2004 Phase 3 (C) Cisplatin & Vinorelbine; 3 out of 4 weeks Did not meet primary endpoint of OS Less toxic

Chemotherapy

21-day cycle for 6 cycles (Gridelli et al. 2003) or up to 9 cycles (Georgoulias et al. 2005)


Regimen variant #4, 80/30, weekly vinorelbine

Study Years of enrollment Evidence Comparator Comparative Efficacy
Depierre et al. 1994 1989-1991 Phase 3 (E-esc) Vinorelbine Superior TTP
Souquet et al. 2002 (GLOB-1) 1998-1999 Phase 3 (C) NIP Did not meet primary endpoint of OS1

Chemotherapy

21-day cycles


Regimen variant #5, 100/25

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wozniak et al. 1998 1993-1995 Phase 3 (E-RT-esc) Cisplatin Superior OS
Kelly et al. 2001 (SWOG 9509) 1996-1998 Phase 3 (C) Carboplatin & Paclitaxel Did not meet primary endpoint of OS
Scagliotti et al. 2002 1998-2000 Phase 3 (C) 1. Carboplatin & Paclitaxel
2. Cisplatin & Gemcitabine 		Did not meet primary endpoint of ORR
Fossella et al. 2003 (TAX 326) 1998-2000 Phase 3 (C) 1. Carboplatin & Docetaxel Did not meet primary endpoint of OS
2. Cisplatin & Docetaxel Seems to have inferior OS
Ramlau et al. 2008 (SPIRIT I) 2003-NR Phase 3 (C) CVb & Bexarotene Did not meet primary endpoint of OS

Chemotherapy

28-day cycle for up to 10 cycles (SWOG 9509) or indefinitely (TAX 326, SPIRIT I)


Regimen variant #6, 100/30

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pujol et al. 2005 1999-2001 Phase 3 (C) Docetaxel & Gemcitabine Did not meet primary endpoint of OS

Chemotherapy

28-day cycle for 6 cycles


Regimen variant #7, 120/30

Study Years of enrollment Evidence Comparator Comparative Efficacy
Le Chevalier et al. 1994 1989-1991 Phase 3 (E-RT-esc) 1. Cisplatin & Vindesine Seems to have superior OS
2. Vinorelbine Superior OS
Comella et al. 2000 1997-1999 Phase 3 (C) 1. Cisplatin & Gemcitabine Not reported
2. PGV Inferior OS

Note: in Comella et al. 2000, vinorelbine was given for a total of 10 weeks.

Chemotherapy

28-day cycle for 1 cycle, then 42-day cycles (see note)

References

  1. Depierre A, Chastang C, Quoix E, Lebeau B, Blanchon F, Paillot N, Lemarie E, Milleron B, Moro D, Clavier J, Herman D, Tuchais E, Jacoulet P, Brechot JM, Cordier JF, Solal-Celigny P, Badri N, Besenval M. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37-42. link to original article contains dosing details in abstract PubMed
  2. Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. link to original article contains dosing details in abstract PubMed
  3. Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR, Livingston RB; SWOG. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459-65. link to original article PubMed
  4. Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G; Southern Italy Cooperative Oncology Group. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol. 2000 Apr;18(7):1451-7. link to original article contains dosing details in manuscript PubMed
  5. SWOG 9509: Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. link to original article contains dosing details in manuscript PubMed
  6. Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. link to original article PubMed
  7. GLOB-1: Souquet PJ, Tan EH, Rodrigues Pereira J, Van Klaveren R, Price A, Gatzemeier U, Jaworski M, Burillon JP, Aubert D. GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients. Ann Oncol. 2002 Dec;13(12):1853-61. Erratum in: Ann Oncol. 2003 Feb;14(2):347. link to original article contains dosing details in abstract PubMed
  8. TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains dosing details in abstract PubMed
  9. NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00004100
  10. Martoni A, Marino A, Sperandi F, Giaquinta S, Di Fabio F, Melotti B, Guaraldi M, Palomba G, Preti P, Petralia A, Artioli F, Picece V, Farris A, Mantovani L. Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer. Eur J Cancer. 2005 Jan;41(1):81-92. link to original article contains dosing details in abstract PubMed
  11. Georgoulias V, Ardavanis A, Tsiafaki X, Agelidou A, Mixalopoulou P, Anagnostopoulou O, Ziotopoulos P, Toubis M, Syrigos K, Samaras N, Polyzos A, Christou A, Kakolyris S, Kouroussis C, Androulakis N, Samonis G, Chatzidaki D. Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2005 May 1;23(13):2937-45. Epub 2005 Feb 22. link to original article contains dosing details in manuscript PubMed
  12. Pujol JL, Breton JL, Gervais R, Rebattu P, Depierre A, Morère JF, Milleron B, Debieuvre D, Castéra D, Souquet PJ, Moro-Sibilot D, Lemarié E, Kessler R, Janicot H, Braun D, Spaeth D, Quantin X, Clary C. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005 Apr;16(4):602-10. Epub 2005 Mar 1. link to original article contains dosing details in manuscript PubMed
  13. FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article contains dosing details in manuscript PubMed
  14. Gebbia V, Galetta D, Lorusso V, Caruso M, Verderame F, Pezzella G, Borsellino N, Durini E, Valenza R, Agostara B, Colucci G; Gruppo Oncologico Italia Meridionale. Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the GOIM (Gruppo Oncologico Italia Meridionale). Lung Cancer. 2008 Sep;61(3):369-77. Epub 2008 Mar 4. link to original article contains dosing details in abstract PubMed
  15. SPIRIT I: Ramlau R, Zatloukal P, Jassem J, Schwarzenberger P, Orlov SV, Gottfried M, Rodrigues Pereira J, Temperley G, Negro-Vilar R, Rahal S, Zhang JK, Negro-Vilar A, Dziewanowska ZE. Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. J Clin Oncol. 2008 Apr 10;26(11):1886-92. link to original article contains dosing details in manuscript PubMed NCT00050973
  16. FLEX: Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article contains dosing details in manuscript PubMed NCT00148798
  17. WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article contains dosing details in manuscript PubMed NCT00144066

Cisplatin, Vinorelbine, Cetuximab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pirker et al. 2009 (FLEX) 2004-2006 Phase 3 (E-esc) Cisplatin & Vinorelbine Seems to have superior OS

Chemotherapy

Targeted therapy

  • Cetuximab (Erbitux) as follows:
    • Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15
    • Cycles 2 to 6: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15

21-day cycle for up to 6 cycles

Subsequent treatment

References

  1. FLEX: Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article contains dosing details in abstract PubMed NCT00148798

Docetaxel & Vinorelbine

Regimen

Study Evidence
Miller et al. 2000 Phase 2

Chemotherapy

References

  1. Miller VA, Krug LM, Ng KK, Pizzo B, Perez W, Heelan RT, Kris MG. Phase II trial of docetaxel and vinorelbine in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Mar;18(6):1346-50. link to original article PubMed

Gemcitabine & Paclitaxel

GT: Gemcitabine & Taxol (Paclitaxel)

Regimen variant #1, 1000/125

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kosmidis et al. 2002 1998-2000 Phase 3 (E-switch-ic) Carboplatin & Paclitaxel Did not meet primary endpoint of OS
Kosmidis et al. 2007 2000-2004 Phase 3 (E-switch-ic) Carboplatin & Gemcitabine Did not meet primary endpoint of OS
Comella et al. 2006 (SICOG 0101) 2001-2005 Phase 3 (C) 1. GV
2. PGT
3. PGV 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #2, 1000/200

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kosmidis et al. 2010 2004-2008 Phase 3 (C) Paclitaxel & Vinorelbine Did not meet primary endpoint of OS

Chemotherapy

21-day cycles

References

  1. Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. link to original article contains dosing details in abstract PubMed
  2. SICOG 0101: Comella P, Filippelli G, De Cataldis G, Massidda B, Frasci G, Maiorino L, Putzu C, Mancarella S, Palmeri S, Cioffi R, Roselli M, Buzzi F, Milia V, Gambardella A, Natale D, Bianco M, Ghiani M, Masullo P; Southern Italy Cooperative Oncology Group. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann Oncol. 2007 Feb;18(2):324-30. Epub 2006 Oct 27. link to original article contains dosing details in abstract PubMed
  3. Kosmidis PA, Fountzilas G, Eleftheraki AG, Kalofonos HP, Pentheroudakis G, Skarlos D, Dimopoulos MA, Bafaloukos D, Pectasides D, Samantas E, Boukovinas J, Lambaki S, Katirtzoglou N, Bakogiannis C, Syrigos KN; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus paclitaxel and vinorelbine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2011 Apr;22(4):827-34. Epub 2010 Sep 29. link to original article contains dosing details in abstract PubMed ACTRN12609000946213

Gemcitabine & Vinorelbine

VG: Vinorelbine & Gemcitabine
GV: Gemcitabine & Vinorelbine
G+V: Gemcitabine & Vinorelbine

Regimen variant #1, 1000/25, 2 weeks out of 3 (IV vinorelbine)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Laack et al. 2004 1999-2001 Phase 3 (E-de-esc) GVP Did not meet primary endpoint of OS
Tan et al. 2005 (GLOB 2) 2000-2002 Phase 3 (E-switch-ic) Carboplatin & Vinorelbine Did not meet primary endpoint of ORR

Chemotherapy

Supportive therapy

  • "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycles


Regimen variant #2, 1000/25, 3 weeks out of 4 (IV vinorelbine)

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Greco et al. 2007 (SCRI LUN 54) 1998-2005 Phase 3 (E-switch-ic) PCG Did not meet primary endpoint of OS Less toxic

Chemotherapy

28-day cycles


Regimen variant #3, 1000/60 (PO vinorelbine)

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fløtten et al. 2012 2007-2009 Phase 3 (E-switch-ic) Carboplatin & Vinorelbine Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for 3 cycles


Regimen variant #4, 1200/30

Study Years of enrollment Evidence Comparator Comparative Efficacy
Frasci et al. 2001 NR Phase 3 (E-esc) Vinorelbine Superior OS

Chemotherapy

21-day cycles

References

  1. Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, DeCataldis G, Belli M, Iannelli N, Massidda B, Mascia V, Comella G, De Lena M; Southern Italy Cooperative Oncology Group. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer: a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer. 2001 Dec;34 Suppl 4:S65-9. link to original article contains dosing details in abstract PubMed
  2. NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00004100
  3. Laack E, Dickgreber N, Müller T, Knuth A, Benk J, Lorenz C, Gieseler F, Dürk H, Engel-Riedel W, Dalhoff K, Kortsik C, Graeven U, Burk M, Dierlamm T, Welte T, Burkholder I, Edler L, Hossfeld DK; German and Swiss Lung Cancer Study Group. Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group. J Clin Oncol. 2004 Jun 15;22(12):2348-56. link to original article contains dosing details in abstract PubMed
  4. GLOB 2: Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. link to original article contains dosing details in abstract PubMed
  5. SCRI LUN 54: Greco FA, Spigel DR, Kuzur ME, Shipley D, Gray JR, Thompson DS, Burris HA, Yardley DA, Pati A, Webb CD, Gandhi JG, Hainsworth JD. Paclitaxel/Carboplatin/gemcitabine versus gemcitabine/vinorelbine in advanced non-small-cell lung cancer: a phase II/III study of the Minnie Pearl Cancer Research Network. Clin Lung Cancer. 2007 Sep;8(8):483-7. link to original article PubMed NCT00193362
  6. Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. link to original article link to PMC article contains dosing details in abstract PubMed NCT00737867

Ipilimumab & Nivolumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hellmann et al. 2018 (CheckMate 227) 2015-2016 Phase 3 (E-RT-switch-ooc) 1. Nivolumab Not reported
2. Platinum doublet Superior OS1
Median OS: 17.1 vs 14.9 mo

1Reported efficacy is based on the 2019 update. Note that the proportional hazards assumption was not met; HR is therefore not reported here.

Biomarker eligibility criteria

  • PD-L1 expression of 1% or more

Immunotherapy

42-day cycles

References

  1. CheckMate 227: Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. link to original article contains dosing details in manuscript PubMed NCT02477826
    1. Update: Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. Epub 2019 Sep 28. link to original article PubMed

Nivolumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Carbone et al. 2017 (CheckMate 026) 2014-2015 Phase 3 (E-switch-ooc) Platinum doublet Did not meet primary endpoint of PFS

Note: control arm patients in CheckMate 026 received investigator's choice of platinum doublet; the most commonly used regimen was carboplatin & paclitaxel.

Immunotherapy

  • Nivolumab (Opdivo) 3 mg/kg IV once on day 1
    • Notably, on 9/13/16 the FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.

14-day cycles

References

  1. CheckMate 026: Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426. link to original articlecontains dosing details in manuscript PubMed NCT02041533
  2. CheckMate 227: Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. link to original article contains dosing details in manuscript PubMed NCT02477826

PCG (Carboplatin)

PCG: Paclitaxel, Carboplatin, Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Paccagnella et al. 2006 1998-2004 Phase 2/3 (E-esc) CP Seems to have superior OS

Chemotherapy

Supportive therapy

21-day cycle for at least 6 cycles

References

  1. Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. link to original article contains dosing details in manuscript PubMed

Pembrolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Garon et al. 2015 (KEYNOTE-001) 2012-2014 Phase 1, >20 pts in dosing cohort
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Phase 3 (E-RT-switch-ooc) 1. Carboplatin & Gemcitabine
2. Carboplatin & Paclitaxel
3. Carboplatin & Pemetrexed
4. Cisplatin & Gemcitabine
5. Cisplatin & Pemetrexed 		Superior OS1
Median OS: 26.3 vs 13.4 mo
(HR 0.62, 95% CI 0.48-0.81) 		Superior HRQoL
Mok et al. 2019 (KEYNOTE-042) 2014-2017 Phase 3 (E-RT-switch-ooc) 1. Carboplatin & Paclitaxel
2. Carboplatin & Pemetrexed 		Superior OS2
Median OS: 16.7 vs 12.1 mo
(HR 0.81, 95% CI 0.71-0.93)
Boyer et al. 2021 (KEYNOTE-598) 2018-2019 Phase 3 (C) Ipilimumab & Pembrolizumab Did not meet primary endpoints of PFS/OS
Awaiting publication (INTR@PID Lung 037) 2018-2021 Phase 3 (C) Bintrafusp alfa TBD
Awaiting publication (LEAP-007) 2019-2021 Phase 3 (C) Lenvatinib & Pembrolizumab TBD
Awaiting publication (AdvanTIG-302) 2021-2025 Phase 3 (C) Ociperlimab & Tislelizumab TBD
Awaiting publication (MK-7684A-003) 2021-2026 Phase 3 (C) Pembrolizumab & Vibostolimab TBD

1Reported efficacy for KEYNOTE-024 is based on the 2021 update.
2Reported efficacy for KEYNOTE-042 is for the population with TPS of 1% or more.
KEYNOTE-024 treatment choice for patients in the comparator arm was up to the investigators; most with nonsquamous histology received carboplatin & pemetrexed, whereas most with squamous histology received carboplatin & gemcitabine. Patients could receive a maximum of 35 cycles. ORR was 45% (95% CI: 37-53).
KEYNOTE-042 treatment choice for patients in the comparator arm was carboplatin & paclitaxel for patients with squamous histology, and carboplatin & pemetrexed for patients with nonsquamous histology.

Biomarker eligibility criteria

  • KEYNOTE-024: PD-L1 to be expressed on at least 50% of tumor cells, no EGFR/ALK mutations
  • KEYNOTE-042: PD-L1 to be expressed on at least 1% of tumor cells
  • KEYNOTE-598: PD-L1 TPS of 50% or more; no sensitizing EGFR or ALK mutations

Immunotherapy

21-day cycle for up to 35 cycles

References

  1. KEYNOTE-001: Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. link to original article PubMed NCT01295827
  2. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
  3. KEYNOTE-042: Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. link to original article PubMed NCT02220894
  4. KEYNOTE-598: Boyer M, Şendur MAN, Rodríguez-Abreu D, Park K, Lee DH, Çiçin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jul 20;39(21):2327-2338. Epub 2021 Jan 29. link to original article contains dosing details in manuscript PubMed NCT03302234
  5. AdvanTIG-302: NCT04746924
  6. INTR@PID Lung 037: NCT03631706
  7. LEAP-007: NCT03829332
  8. MK-7684A-003: NCT04738487

Advanced or metastatic disease, first-line, elderly or poor performance status

Carboplatin & Gemcitabine (GCb)

CG: Carboplatin & Gemcitabine

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Biesma et al. 2011 (NVALT-3) 2003-2006 Phase 3 (C) CP Similar QoL

Chemotherapy

21-day cycle for up to 4 cycles

References

  1. NVALT-3: Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. link to original article contains dosing details in manuscript PubMed NTR925

Carboplatin & Paclitaxel (CP)

TC: Taxol (Paclitaxel) & Carboplatin
CP: Carboplatin & Paclitaxel

Regimen variant #1, 5/175

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Biesma et al. 2011 (NVALT-3) 2003-2006 Phase 3 (C) CG Similar QoL

Chemotherapy

21-day cycle for up to 4 cycles


Regimen variant #2, 6/90

Study Years of enrollment Evidence Comparator Comparative Efficacy
Quoix et al. 2011 (IFCT-0501) 2006-2009 Phase 3 (E-esc) 1. Gemcitabine
2. Vinorelbine 		Superior OS
Median OS: 10.3 vs 6.2 mo
(HR 0.64, 95% CI 0.52-0.78)

Study involved only patients 70 to 89 years old

Chemotherapy

Supportive therapy

  • Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3-4 neutropenia

28-day cycle for up to 4 cycles


Regimen variant #3, 6/200

Study Years of enrollment Evidence Comparator Comparative Efficacy
Lilenbaum et al. 2008 2002-2004 Phase 3 (C) Erlotinib Seems to have superior OS

Chemotherapy

21-day cycle for up to 4 cycles


Regimen variant #4, 6/225

Study Years of enrollment Evidence Comparator Comparative Efficacy
Langer et al. 2008 2002-2003 Phase 3 (C) Carboplatin & PPX Did not meet primary endpoint of OS

Chemotherapy

21-day cycles

References

  1. Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. link to original article contains dosing details in abstract PubMed
  2. Langer CJ, O'Byrne KJ, Socinski MA, Mikhailov SM, Leśniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6):623-30. link to original article contains dosing details in abstract PubMed
  3. NVALT-3: Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. link to original article contains dosing details in manuscript PubMed NTR925
  4. IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains dosing details in manuscript PubMed NCT00298415

Carboplatin & Pemetrexed

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Zukin et al. 2013 (INCA-Lung001) 2008-2011 Phase 3 (E-esc) Pemetrexed Superior OS
Median OS: 9.3 vs 5.3 mo
(HR 0.62, 95% CI 0.46-0.83)

Chemotherapy

Supportive therapy

21-day cycle for up to 4 cycles

References

  1. INCA-Lung001: Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article contains dosing details in manuscript PubMed NCT01836575

Carboplatin, Pemetrexed, Bevacizumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Spigel et al. 2018 (ToPPS) 2009-2013 Randomized Phase 2 (E-esc) 1. Pemetrexed
2. Pemetrexed & Bevacizumab 		PFS: 4.8 mo

Chemotherapy

Targeted therapy

Supportive therapy

  • Premedications, Folic acid (Folate), and vitamin supplementation per standard guidelines
  • Antiemetics per standard guidelines

21-day cycles

References

  1. ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article contains dosing details in manuscript PubMed NCT00892710

Cisplatin & Gemcitabine (GC)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Morabito et al. 2013 (CAPPA-2) 2008-2012 Phase 3 (E-esc) Gemcitabine Seems to have superior OS
Median OS: 5.9 vs 3 mo
(HR 0.52, 95% CI 0.28-0.98)
Gridelli et al. 2018 (MILES-3) 2011-2016 Phase 3 (E-esc) Gemcitabine Did not meet primary endpoint of OS
Gridelli et al. 2018 (MILES-4) 2011-2016 Phase 3 (E-esc) Gemcitabine Did not meet primary endpoint of OS

MILES studies involved only patients at least 70 years old. CAPPA-2 allowed patients aged 18-70 with ECOG PS = 2.

Chemotherapy

References

  1. CAPPA-2: Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. link to original article contains dosing details in abstract PubMed NCT00526643
  2. MILES-3: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article contains dosing details in manuscript PubMed NCT01405586
  3. MILES-4: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article contains dosing details in manuscript PubMed NCT01656551

Docetaxel monotherapy

Example orders

Regimen variant #1, 25 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Tsukada et al. 2014 (JCOG0207) 2003-2006 Phase 3 (C) Cisplatin & Docetaxel Did not meet primary endpoint of OS

Chemotherapy

28-day cycles


Regimen variant #2, 36 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hainsworth et al. 2007 2001-2006 Phase 3 (C) Docetaxel & Gemcitabine Did not meet primary endpoint of OS

Chemotherapy

28-day cycles


Regimen variant #3, 38 mg/m2, 2 out of 3 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Karampeazis et al. 2011 (HORG CT/03.07) 2003-2008 Phase 3 (E-switch-ic) Vinorelbine Might have superior OS

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #4, 60 mg/m2 q3wk

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kudoh et al. 2006 (WJTOG 9904) 2000-2003 Phase 3 (E-switch-ic) Vinorelbine Did not meet primary endpoint of OS
Abe et al. 2015 (JCOG0803/WJOG4307L) 2008-2010 Phase 3 (C) Cisplatin & Docetaxel Did not meet primary endpoint of OS

Note: This is the PMDA-approved dose.

Chemotherapy

21-day cycle for up to 4 cycles (WJTOG 9904) or indefinitely

References

  1. WJTOG 9904: Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. link to original article contains dosing details in abstract PubMed NCT00148291
  2. Hainsworth JD, Spigel DR, Farley C, Shipley DL, Bearden JD, Gandhi J, Houston GA, Greco FA. Weekly docetaxel versus docetaxel/gemcitabine in the treatment of elderly or poor performance status patients with advanced nonsmall cell lung cancer: a randomized phase 3 trial of the Minnie Pearl Cancer Research Network. Cancer. 2007 Nov 1;110(9):2027-34. link to original article contains dosing details in abstract PubMed
  3. HORG CT/03.07: Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. link to original article contains dosing details in manuscript PubMed NCT00441922
  4. JCOG0207: Tsukada H, Yokoyama A, Goto K, Shinkai T, Harada M, Ando M, Shibata T, Ohe Y, Tamura T, Saijo N; Lung Cancer Study Group of the Japan Clinical Oncology Group (JCOG). Randomized controlled trial comparing docetaxel-cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small-cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207. Jpn J Clin Oncol. 2015 Jan;45(1):88-95. Epub 2014 Nov 6. link to original article contains dosing details in abstract PubMed UMIN C000000146
  5. JCOG0803/WJOG4307L: Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Mizusawa J, Shibata T, Nakamura S, Ando M, Yokoyama A, Nakagawa K, Saijo N, Tamura T. Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol. 2015 Feb 20;33(6):575-81. Epub 2015 Jan 12. link to original article contains dosing details in manuscript PubMed UMIN000001424

Gemcitabine monotherapy

Regimen variant #1, 1000 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
O'Brien et al. 2008 2002-2004 Phase 3 (C) Paclitaxel poliglumex Did not meet primary endpoint of OS

Chemotherapy

28-day cycle for up to 6 cycles


Regimen variant #2, 1150 mg/m2, 2 out of 3 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Quoix et al. 2011 (IFCT-0501) 2006-2009 Phase 3 (C) Carboplatin & Paclitaxel Inferior OS

Study involved only patients 70 to 89 years old

Chemotherapy

Supportive therapy

  • Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia

21-day cycle for up to 5 cycles


Regimen variant #3, 1200 mg/m2, 2 out of 3 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gridelli et al. 2003 (MILES) 1997-2000 Phase 3 (E-switch-ic) 1. Gemcitabine & Vinorelbine Did not meet primary endpoint of OS
2. Vinorelbine Did not meet primary endpoint of OS
Reynolds et al. 2009 (USO-03012) 2004-2006 Phase 3 (C) Carboplatin & Gemcitabine Did not meet primary endpoint of OS
Morabito et al. 2013 (CAPPA-2) 2008-2012 Phase 3 (C) Cisplatin & Gemcitabine Seems to have inferior OS
Gridelli et al. 2018 (MILES-3) 2011-2016 Phase 3 (C) Cisplatin & Gemcitabine Did not meet primary endpoint of OS
Gridelli et al. 2018 (MILES-4) 2011-2016 Phase 3 (C) Cisplatin & Gemcitabine Did not meet primary endpoint of OS

MILES studies involved only patients at least 70 years old. CAPPA-2 allowed patients aged 18-70 with ECOG PS = 2.

Chemotherapy

Supportive therapy

  • "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycle for 4 to 6 cycles

References

  1. MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains dosing details in manuscript PubMed NCT00003447
  2. SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article contains dosing details in abstract PubMed
  3. O'Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, Hotko YS, Ganul VL, Kostinsky IY, Eisenfeld AJ, Sandalic L, Oldham FB, Bandstra B, Sandler AB, Singer JW. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):728-34. link to original article contains dosing details in manuscript PubMed
  4. USO-03012: Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, Caton JR, Demarco LC, O'Rourke MA, Shaw Wright G, Boehm KA, Asmar L, Bromund J, Peng G, Monberg MJ, Bepler G. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol. 2009 Dec 1;27(34):5808-15. Epub 2009 Nov 2. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00190710
  5. IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains dosing details in manuscript PubMed NCT00298415
  6. CAPPA-2: Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. link to original article contains dosing details in abstract PubMed NCT00526643
  7. MILES-3: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article contains dosing details in manuscript PubMed NCT01405586
  8. MILES-4: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article contains dosing details in manuscript PubMed NCT01656551
  9. IPSOS: NCT03191786

Gemcitabine & Paclitaxel

GT: Gemcitabine & Taxol (Paclitaxel)

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Comella et al. 2004 (SICOG 9909) 1999-2003 Phase 3 (E-esc) 1. Gemcitabine
2. Paclitaxel 		Seems to have superior OS
3. GV Not reported

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article contains dosing details in abstract PubMed

Gemcitabine & Vinorelbine

GV: Gemcitabine & Vinorelbine
VG: Vinorelbine & Gemcitabine

Regimen variant #1, 1000/25

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gridelli et al. 2003 (MILES) 1997-2000 Phase 3 (E-esc) 1. Gemcitabine Did not meet primary endpoint of OS
2. Vinorelbine Did not meet primary endpoint of OS

Eligibility criteria

  • At least 70 years old

Chemotherapy

Supportive therapy

  • "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycle for up to 6 cycles


Regimen variant #2, 1200/30

Study Years of enrollment Evidence Comparator Comparative Efficacy
Frasci et al. 2000 1997-1999 Phase 3 (E-esc) Vinorelbine Superior OS

Eligibility criteria

  • At least 70 years old

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, De Cataldis G, Iannelli A, Bilancia D, Belli M, Massidda B, Piantedosi F, Comella G, De Lena M. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Jul;18(13):2529-36. link to original article contains dosing details in abstract PubMed
  2. MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains dosing details in manuscript PubMed NCT00003447
  3. SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article contains dosing details in abstract PubMed

Pemetrexed monotherapy

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Zukin et al. 2013 (INCA-Lung001) 2008-2011 Phase 3 (C) Carboplatin & Pemetrexed Inferior OS
Gridelli et al. 2018 (MILES-4) 2011-2016 Phase 3 (C) 1. Cisplatin & Gemcitabine
2. Cisplatin & Pemetrexed 		Did not meet primary endpoint of OS

Chemotherapy

21-day cycle for up to 4 cycles (INCA-Lung001) or 6 cycles (MILES-4)

References

  1. INCA-Lung001: Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article contains dosing details in manuscript PubMed NCT01836575
  2. ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article contains dosing details in manuscript PubMed NCT00892710
  3. MILES-4: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article contains dosing details in manuscript PubMed NCT01656551

Pemetrexed & Bevacizumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Spigel et al. 2018 (ToPPS) 2009-2013 Randomized Phase 2 (E-esc) 1. Pemetrexed
2. Carboplatin, Pemetrexed, Bevacizumab 		PFS: 4.0 mo

Chemotherapy

Targeted therapy

Supportive therapy

  • Premedications, Folic acid (Folate), and vitamin supplementation per standard guidelines
  • Antiemetics per standard guidelines

21-day cycles

References

  1. ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article contains dosing details in manuscript PubMed NCT00892710

Vinorelbine monotherapy

Regimen variant #1, 25 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kudoh et al. 2006 (WJTOG 9904) 2000-2003 Phase 3 (C) Docetaxel Did not meet primary endpoint of OS
Karampeazis et al. 2011 (HORG CT/03.07) 2003-2008 Phase 3 (E-switch-ic) Docetaxel Might have inferior OS
Quoix et al. 2011 (IFCT-0501) 2006-2009 Phase 3 (C) Carboplatin & Paclitaxel Inferior OS

IFCT-0501 involved only patients 70 to 89 years old

Chemotherapy

Supportive therapy

  • Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia

21-day cycle for up to 4 cycles (WJTOG 9904), 5 cycles (IFCT-0501), or 6 cycles (HORG CT/03.07)


Regimen variant #2, 30 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gridelli et al. 1999 (ELVIS) 1996-1997 Phase 3 (E-esc) Best supportive care Seems to have superior OS
Gridelli et al. 2003 (MILES) 1997-2000 Phase 3 (C) 1. Gemcitabine Did not meet primary endpoint of OS
2. Gemcitabine & Vinorelbine Did not meet primary endpoint of OS

Study involved only patients at least 70 years old

Chemotherapy

Supportive therapy

21-day cycle for up to 6 cycles

References

  1. ELVIS: Gridelli C, Perrone F, Gallo C; Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. link to original article contains dosing details in manuscript PubMed
  2. MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains dosing details in manuscript PubMed NCT00003447
  3. WJTOG 9904: Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. link to original article contains dosing details in abstract PubMed NCT00148291
  4. HORG CT/03.07: Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. link to original article contains dosing details in manuscript PubMed NCT00441922
  5. IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains dosing details in manuscript PubMed NCT00298415
  6. IPSOS: NCT03191786

Maintenance after first-line therapy

Bevacizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Johnson et al. 2013 (ATLAS-NSCLC) 2006-2009 Phase 3 (C) Erlotinib & Bevacizumab maintenance Inferior PFS1 Less toxic

1While this arm was inferior in ATLAS, the authors note that, due to toxicity, the "two-drug maintenance regimen will not lead to a new postchemotherapy standard of care."
Note: This trial should not be confused with the ones with the same name in breast cancer and in renal cell carcinoma.

Preceding treatment

Targeted therapy

21-day cycles

References

  1. ATLAS: Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34. Epub 2013 Oct 7. link to original article contains dosing details in supplement PubMed NCT00257608

Docetaxel monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Zhang et al. 2021 (TFINE) 2009-2011 Phase 3 (E-esc) Observation Superior PFS
Median PFS: 5.8 vs 3 mo
(HR 0.57, 95% CI 0.40-0.80)

Preceding treatment

  • DC; DC60 x 4 versus DC; DC75 x 4

Chemotherapy

21-day cycle for up to 6 cycles

References

  1. TFINE:' Zhang L, Lu S, Cheng Y, Hu Z, Wu YL, Chen Z, Chen G, Liu X, Yang J, Zhang L, Chen J, Huang M, Tao M, Cheng G, Huang C, Zhou C, Zhang W, Zhao H, Sun Y. Docetaxel maintenance therapy versus best supportive care after first-line chemotherapy with different dose docetaxel plus cisplatin for advanced non-small cell lung cancer (TFINE study, CTONG-0904): an open-label, randomized, phase III trial. Ann Transl Med. 2021 Feb;9(4):338. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01038661

Gemcitabine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Brodowicz et al. 2006 1999-2002 Phase 3 (E-esc) Observation Superior TTP
Pérol et al. 2012 (IFCT-GFPC 0502) 2006-2009 Phase 3 (E-esc) 1. Erlotinib Not reported
2. Observation Superior PFS
Median PFS: 3.8 vs 1.9 mo
(HR 0.56, 95% CI 0.44-0.72)

Preceding treatment

Chemotherapy

21-day cycles

References

  1. Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, Ciuleanu T, Cucevic B, Gyurkovits K, Ulsperger E, Jassem J, Grgic M, Saip P, Szilasi M, Wiltschke C, Wagnerova M, Oskina N, Soldatenkova V, Zielinski C, Wenczl M; Central European Cooperative Oncology Group. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006 May;52(2):155-63. Epub 2006 Mar 29. link to original article contains dosing details in abstract PubMed
  2. IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original articlecontains dosing details in manuscript PubMed NCT00300586

Ipilimumab monotherapy

Regimen

Study Evidence
Lynch et al. 2012 (CA184-041) Non-randomized portion of phase 2 RCT

Preceding treatment

Immunotherapy

12-week cycles

References

  1. CA184-041: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains dosing details in manuscript PubMed NCT00527735

Pembrolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (ZEAL-1L) 2020-ongoing Phase 3 (C) Niraparib & Pembrolizumab In progress

Preceding treatment

Immunotherapy

21-day cycles

References

  1. ZEAL-1L: NCT04475939

Pemetrexed monotherapy

Example orders

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Ciuleanu et al. 2009 (JMEN) 2005-2007 Phase 3 (E-RT-esc) Placebo Superior OS
Median OS: 13.4 vs 10.6 mo
(HR 0.79, 95% CI 0.65-0.95)
Reck et al. 2016 (KEYNOTE-024) 2014-2015 Non-randomized portion of phase 3 RCT
Mok et al. 2019 (KEYNOTE-042) 2014-2017 Non-randomized portion of phase 3 RCT
Gandhi et al. 2018 (KEYNOTE-189) 2016-2017 Non-randomized portion of phase 3 RCT

Preceding treatment

Chemotherapy

Supportive therapy

21-day cycles

References

  1. JMEN: Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Rodrigues Pereira J, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. Epub 2009 Sep 18. link to original article contains dosing details in abstract PubMed NCT00102804
  2. KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT02142738
    1. HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
    2. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
    3. Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
  3. KEYNOTE-189: Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Epub 2018 Apr 16. link to original article link to protocol contains dosing details in manuscript PubMed NCT02578680
  4. KEYNOTE-042: Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. link to original article PubMed NCT02220894

Pemetrexed & Pembrolizumab

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gandhi et al. 2018 (KEYNOTE-189) 2016-2017 Phase 3 (E-esc) See link See link

Preceding treatment

Immunotherapy

Chemotherapy

Supportive therapy

21-day cycle for up to 2 years (35 cycles total, including induction)

Subsequent treatment

References

  1. KEYNOTE-189: Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SY, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC; KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med. 2018 May 31;378(22):2078-2092. Epub 2018 Apr 16. link to original article link to protocol contains dosing details in manuscript PubMed NCT02578680

Advanced or metastatic disease, second-line

Cabozantinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Neal et al. 2016 (ECOG-ACRIN 1512) 2013-2014 Randomized Phase 2 (E-switch-ic) 1. Cabozantinib & Erlotinib Not reported
2. Erlotinib Superior PFS

Targeted therapy

Continued indefinitely

References

  1. ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT01708954

Cabozantinib & Erlotinib

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Neal et al. 2016 (ECOG-ACRIN 1512) 2013-2014 Randomized Phase 2 (E-esc) 1. Cabozantinib Not reported
2. Erlotinib Superior PFS

Targeted therapy

Continued indefinitely

References

  1. ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT01708954

Carboplatin & Pemetrexed

Example orders

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Ardizzoni et al. 2012 (GOIRC 02-2006) 2007-2009 Randomized Phase 2 (E-esc) Pemetrexed Did not meet primary endpoint of PFS

Chemotherapy

Supportive therapy

21-day cycle for 4 to 6 cycles

References

  1. GOIRC 02-2006: Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. link to original article contains dosing details in manuscript PubMed NCT00786331

Docetaxel monotherapy

Example orders

Regimen variant #1, 33.3 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Gebbia et al. 2008 (DISTAL-2) 2005-2006 Phase 3 (C) 1. Capecitabine & Docetaxel
2.Docetaxel & Gemcitabine
3. Docetaxel & Vinorelbine 		Did not meet primary endpoint of OS

Chemotherapy

28-day cycles


Regimen variant #2, 35 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Schuette et al. 2005 2000-2003 Phase 3 (E-switch-ic) Docetaxel; 75 mg/m2, every 3 wks Might have superior OS
Garassino et al. 2013 (TAILORNSCLC) 2007-2012 Phase 3 (C) Erlotinib Seems to have superior OS

Note that there is another trial named TAILOR in colorectal cancer.

Chemotherapy

Supportive therapy

28-day cycles


Regimen variant #3, 50 mg/m2 q2wk, limited duration

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pallis et al. 2010 (HORG CT/04.14) 2004-2008 Phase 3 (C) Carboplatin & Docetaxel Did not meet primary endpoint of OS

Prior treatment criteria

  • Previous treatment with a platinum-free regimen

Chemotherapy

28-day cycle for up to 6 cycles


Regimen variant #4, 60 mg/m2 q3wk, limited duration

Study Years of enrollment Evidence Comparator Comparative Efficacy
Herbst et al. 2010 (ZODIAC) 2006-2008 Phase 3 (C) Docetaxel & Vandetanib Inferior PFS

Note: This is the PMDA-approved dose. While statistically inferior, the median PFS difference was only 0.8 months.

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #5, 60 mg/m2 q3wk, indefinite

Study Years of enrollment Evidence Comparator Comparative Efficacy
Takeda et al. 2009 (JCOG 0104) 2002-2003 Phase 3 (C) Docetaxel & Gemcitabine Did not meet primary endpoint of OS
Kawaguchi et al. 2014 (DELTANSCLC) 2009-2012 Phase 3 (C) Erlotinib Might have superior PFS
Garon et al. 2014 (REVEL) 2010-2013 Phase 3 (C) Docetaxel & Ramucirumab Seems to have inferior OS
Gridelli et al. 2018 (AvaALL) 2011-2015 Phase 3 (C) Investigator's choice of:
1. Docetaxel & Bevacizumab
2. Erlotinib & Bevacizumab
3. Pemetrexed & Bevacizumab 		Did not meet primary endpoint of OS

Note: This is the PMDA-approved dose, the dose used for East Asian patients in REVEL, and the dose used in Japanese patients in EAST-LC. Note that there is another trial named DELTA in indolent lymphoma.

Chemotherapy

21-day cycles


Regimen variant #6, 75 mg/m2 q3wk, limited duration

Study Years of enrollment Evidence Comparator Comparative Efficacy
Herbst et al. 2010 (ZODIAC) 2006-2008 Phase 3 (C) Docetaxel & Vandetanib Inferior PFS

Note: while statistically inferior, the median PFS difference in ZODIAC was only 0.8 months.

Chemotherapy

21-day cycle for up to 6 cycles


Regimen variant #7, 75 mg/m2 q3wk, indefinite

Study Years of enrollment Evidence Comparator Comparative Efficacy Comparative Toxicity
Gridelli et al. 2004 (DISTAL 01) 2000-2002 Phase 3 (C) Docetaxel; 33.3 mg/m2, 6 out of 8 wks Did not meet primary endpoint of QoL
Schuette et al. 2005 2000-2003 Phase 3 (C) Docetaxel; 35 mg/m2, 3 out of 4 wks Might have inferior OS
Paz-Ares et al. 2008 (STELLAR 2) 2002-2004 Phase 3 (C) Paclitaxel poliglumex Did not meet primary endpoint of OS
Krzakowski et al. 2010 2003-2005 Phase 3 (C) Vinflunine Non-inferior PFS
Sun et al. 2012 (JMID) 2006-2008 Phase 3 (C) Pemetrexed Inconclusive whether non-inferior OS
Ciuleanu et al. 2012 (TITAN) 2006-2010 Phase 3 (C) Erlotinib Did not meet primary endpoint of OS
Garassino et al. 2013 (TAILORNSCLC) 2007-2012 Phase 3 (C) Erlotinib Seems to have superior OS
Garon et al. 2014 (REVEL) 2010-2013 Phase 3 (C) Docetaxel & Ramucirumab Seems to have inferior OS
Gridelli et al. 2018 (AvaALL) 2011-2015 Phase 3 (C) Investigator's choice of:
1. Docetaxel & Bevacizumab
2. Erlotinib & Bevacizumab
3. Pemetrexed & Bevacizumab 		Did not meet primary endpoint of OS
Pillai et al. 2019 (GALAXY-2) 2013-2015 Phase 3 (C) Docetaxel & Ganetespib Did not meet primary endpoint of OS

Chemotherapy

Supportive therapy

21-day cycles

References

  1. DISTAL 01: Gridelli C, Gallo C, Di Maio M, Barletta E, Illiano A, Maione P, Salvagni S, Piantedosi FV, Palazzolo G, Caffo O, Ceribelli A, Falcone A, Mazzanti P, Brancaccio L, Capuano MA, Isa L, Barbera S, Perrone F. A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer: the DISTAL 01 study. Br J Cancer. 2004 Dec 13;91(12):1996-2004. link to original article link to PMC article contains dosing details in abstract PubMed
  2. Schuette W, Nagel S, Blankenburg T, Lautenschlaeger C, Hans K, Schmidt EW, Dittrich I, Schweisfurth H, von Weikersthal LF, Raghavachar A, Reissig A, Serke M. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol. 2005 Nov 20;23(33):8389-95. link to original article contains dosing details in abstract PubMed
  3. STELLAR 2: Paz-Ares L, Ross H, O'Brien M, Riviere A, Gatzemeier U, Von Pawel J, Kaukel E, Freitag L, Digel W, Bischoff H, García-Campelo R, Iannotti N, Reiterer P, Bover I, Prendiville J, Eisenfeld AJ, Oldham FB, Bandstra B, Singer JW, Bonomi P. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer. Br J Cancer. 2008 May 20;98(10):1608-13. Epub 2008 May 13. link to original article link to PMC article contains dosing details in abstract PubMed
  4. DISTAL-2: Gebbia V, Gridelli C, Verusio C, Frontini L, Aitini E, Daniele B, Gamucci T, Mancuso G, Di Maio M, Gallo C, Perrone F, Morabito A. Weekly docetaxel vs docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients: the DISTAL-2 randomized trial. Lung Cancer. 2009 Feb;63(2):251-8. Epub 2008 Jul 15. link to original article contains dosing details in abstract PubMed NCT00345059
  5. JCOG 0104: Takeda K, Negoro S, Tamura T, Nishiwaki Y, Kudoh S, Yokota S, Matsui K, Semba H, Nakagawa K, Takada Y, Ando M, Shibata T, Saijo N. Phase III trial of docetaxel plus gemcitabine versus docetaxel in second-line treatment for non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG0104). Ann Oncol. 2009 May;20(5):835-41. Epub 2009 Jan 22. link to original article contains dosing details in abstract PubMed
  6. Krzakowski M, Ramlau R, Jassem J, Szczesna A, Zatloukal P, Von Pawel J, Sun X, Bennouna J, Santoro A, Biesma B, Delgado FM, Salhi Y, Vaissiere N, Hansen O, Tan EH, Quoix E, Garrido P, Douillard JY. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol. 2010 May 1;28(13):2167-73. Epub 2010 Mar 29. link to original article contains dosing details in abstract PubMed
  7. ZODIAC: Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00312377
    1. Dataset: Project Data Sphere
  8. HORG CT/04.14: Pallis AG, Agelaki S, Agelidou A, Varthalitis I, Syrigos K, Kentepozidis N, Pavlakou G, Kotsakis A, Kontopodis E, Georgoulias V. A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic non-small cell lung cancer. BMC Cancer. 2010 Nov 19;10:633. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00430651
  9. TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article contains dosing details in abstract PubMed NCT00556322
  10. JMID: Sun Y, Wu YL, Zhou CC, Zhang L, Zhang L, Liu XY, Yu SY, Jiang GL, Li K, Qin SK, Ma SL, Han L, Quinlivan M, Orlando M, Zhang XQ. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer. 2013 Feb;79(2):143-50. Epub 2012 Nov 20. link to original article PubMed NCT00391274
  11. TAILOR: Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. link to original article contains dosing details in manuscript PubMed NCT00637910
  12. DELTA: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article contains dosing details in manuscript PubMed
  13. REVEL: Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. link to original article contains dosing details in manuscript PubMed NCT01168973
  14. AvaALL: Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. link to original article link to PMC article contains dosing details in supplement PubMed NCT01351415
  15. GALAXY-2: Pillai RN, Fennell DA, Kovcin V, Ciuleanu TE, Ramlau R, Kowalski D, Schenker M, Yalcin I, Teofilovici F, Vukovic VM, Ramalingam SS. Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2). J Clin Oncol. 2020 Feb 20;38(6):613-622. Epub 2019 Dec 12. link to original article contains dosing details in abstract PubMed NCT01798485
  16. DUBLIN-3: NCT02504489

Docetaxel & Ramucirumab

Regimen variant #1, 60 mg/m2 docetaxel

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Garon et al. 2014 (REVEL) 2010-2013 Phase 3 (E-RT-esc) Docetaxel Seems to have superior OS
Median OS: 10.5 vs 9.1 mo
(HR 0.86, 95% CI 0.75-0.98)

Note: This is the PMDA-approved dose and the dose recommended for East Asians. The FDA only provides recommendations for ramucirumab dosing.

Chemotherapy

Targeted therapy

Supportive therapy

  • Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.

21-day cycles


Regimen variant #2, 75 mg/m2 docetaxel

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Garon et al. 2014 (REVEL) 2010-2013 Phase 3 (E-RT-esc) Docetaxel Seems to have superior OS
Median OS: 10.5 vs 9.1 mo
(HR 0.86, 95% CI 0.75-0.98)

Note: The FDA only provides recommendations for ramucirumab dosing.

Chemotherapy

Targeted therapy

Supportive therapy

  • Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.

21-day cycles

References

  1. REVEL: Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. link to original article contains dosing details in manuscript PubMed NCT01168973

Docetaxel & Vandetanib

Regimen variant #1, 60 mg/m2 docetaxel

Study Years of enrollment Evidence Comparator Comparative Efficacy
Herbst et al. 2010 (ZODIAC) 2006-2008 Phase 3 (E-esc) Docetaxel Superior PFS
Median PFS: 4 vs 3.2 mo
(HR 0.79, 97.58% CI 0.70-0.90)

Note: This is the PMDA-approved dose of docetaxel. While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Chemotherapy

Targeted therapy

21-day cycles


Regimen variant #2, 75 mg/m2 docetaxel

Study Years of enrollment Evidence Comparator Comparative Efficacy
Herbst et al. 2010 (ZODIAC) 2006-2008 Phase 3 (E-esc) Docetaxel Superior PFS
Median PFS: 4 vs 3.2 mo
(HR 0.79, 97.58% CI 0.70-0.90)

While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.

Chemotherapy

Targeted therapy

21-day cycle for up to 6 cycles (see note)

References

  1. ZODIAC: Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00312377

Gefitinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Sun et al. 2012 (KCSG-LU08-01) 2008-2010 Phase 3 (E-switch-ooc) Pemetrexed Superior PFS
Median PFS: 9 vs 3 mo
(HR 0.54, 95% CI 0.37-0.79)

Targeted therapy

Continued indefinitely

References

  1. KCSG-LU08-01: Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, Kim HK, Song HS, Kim YH, Kim BS, Hwang IG, Lee K, Jo SJ, Lee JW, Ahn JS, Park K, Ahn MJ; Korean Cancer Study Group. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012 Dec 15;118(24):6234-42. Epub 2012 Jun 6. link to original article contains dosing details in abstract PubMed NCT01066195

Gemcitabine monotherapy

Regimen

Study Evidence
Crinò et al. 1999a Phase 2

Chemotherapy

28-day cycles

References

  1. Crinò L, Mosconi AM, Scagliotti G, Selvaggi G, Novello S, Rinaldi M, Della Giulia M, Gridelli C, Rossi A, Calandri C, De Marinis F, Noseda M, Tonato M. Gemcitabine as second-line treatment for advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol. 1999 Jul;17(7):2081-5. link to original article contains dosing details in abstract PubMed

Pemetrexed monotherapy

Example orders

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Cullen et al. 2008 (JMGX) 2004-2005 Phase 3 (C) Pemetrexed; high-dose Did not meet primary endpoint of OS
Sun et al. 2012 (JMID) 2006-2008 Phase 3 (E-switch-ic) Docetaxel Inconclusive whether non-inferior OS
Ciuleanu et al. 2012 (TITAN) 2006-2010 Phase 3 (C) Erlotinib Did not meet primary endpoint of OS
de Boer et al. 2011 (ZEAL) 2007-2008 Phase 3 (C) Pemetrexed & Vandetanib Did not meet primary endpoint of PFS
Ardizzoni et al. 2012 (GOIRC 02-2006) 2007-2009 Randomized Phase 2 (C) Carboplatin & Pemetrexed Did not meet primary endpoint of PFS
Sun et al. 2012 (KCSG-LU08-01) 2008-2010 Phase 3 (C) Gefitinib Inferior PFS
Gridelli et al. 2018 (AvaALL) 2011-2015 Phase 3 (C) Investigator's choice of:
1. Docetaxel & Bevacizumab
2. Erlotinib & Bevacizumab
3. Pemetrexed & Bevacizumab 		Did not meet primary endpoint of OS

Chemotherapy

Supportive therapy

21-day cycles GOIRC 02-2006 treated patients for up to 4 cycles or until progressive disease, unacceptable toxicity, or patient refusal.

References

  1. JMGX: Cullen MH, Zatloukal P, Sörenson S, Novello S, Fischer JR, Joy AA, Zereu M, Peterson P, Visseren-Grul CM, Iscoe N. A randomized phase III trial comparing standard and high-dose pemetrexed as second-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2008 May;19(5):939-45. Epub 2008 Feb 17. link to original article contains dosing details in abstract PubMed NCT00078260
  2. ZEAL: de Boer RH, Arrieta Ó, Yang CH, Gottfried M, Chan V, Raats J, de Marinis F, Abratt RP, Wolf J, Blackhall FH, Langmuir P, Milenkova T, Read J, Vansteenkiste JF. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2011 Mar 10;29(8):1067-74. Epub 2011 Jan 31. link to original article contains dosing details in abstract PubMed NCT00418886
  3. TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article contains dosing details in abstract PubMed NCT00556322
  4. KCSG-LU08-01: Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, Kim HK, Song HS, Kim YH, Kim BS, Hwang IG, Lee K, Jo SJ, Lee JW, Ahn JS, Park K, Ahn MJ; Korean Cancer Study Group. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012 Dec 15;118(24):6234-42. Epub 2012 Jun 6. link to original article contains dosing details in abstract PubMed NCT01066195
  5. GOIRC 02-2006: Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. link to original article contains dosing details in manuscript PubMed NCT00786331
  6. JMID: Sun Y, Wu YL, Zhou CC, Zhang L, Zhang L, Liu XY, Yu SY, Jiang GL, Li K, Qin SK, Ma SL, Han L, Quinlivan M, Orlando M, Zhang XQ. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer. 2013 Feb;79(2):143-50. Epub 2012 Nov 20. link to original article PubMed NCT00391274
  7. AvaALL: Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. link to original article link to PMC article contains dosing details in supplement PubMed NCT01351415

Advanced or metastatic disease, third-line

Cabozantinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Neal et al. 2016 (ECOG-ACRIN 1512) 2013-2014 Randomized Phase 2 (E-switch-ic) 1. Cabozantinib & Erlotinib Not reported
2. Erlotinib Superior PFS

Targeted therapy

Continued indefinitely

References

  1. ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT01708954

Cabozantinib & Erlotinib

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Neal et al. 2016 (ECOG-ACRIN 1512) 2013-2014 Randomized Phase 2 (E-esc) 1. Cabozantinib Not reported
2. Erlotinib Superior PFS

Targeted therapy

Continued indefinitely

References

  1. ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article contains dosing details in abstract link to PMC article PubMed NCT01708954

Docetaxel monotherapy

Example orders

Regimen variant #1, 60 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kawaguchi et al. 2014 (DELTANSCLC) 2009-2012 Phase 3 (C) Erlotinib Might have superior PFS

Note: This is the PMDA-approved dose. Note that there is another trial named DELTA in indolent lymphoma.

Chemotherapy

21-day cycles


Regimen variant #2, 75 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Awaiting publication (CANOPY-2) 2019-ongoing Phase 3 (C) Docetaxel & Canakinumab Awaiting results
Awaiting publication (LEAP-008) 2019-ongoing Phase 3 (C) 1. Lenvatinib & Pembrolizumab
2. Lenvatinib 		Awaiting results
Awaiting publication (SAPPHIRE) 2019-ongoing Phase 3 (C) Sitravantinib & Nivolumab Awaiting results
Awaiting publication (CONTACT-01) 2020-ongoing Phase 3 (C) Cabozantinib & Atezolizumab Awaiting results

Chemotherapy

21-day cycles

References

  1. DELTA: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article contains dosing details in manuscript PubMed
  2. CANOPY-2: NCT03626545
  3. CONTACT-01: NCT04471428
  4. LEAP-008: NCT03976375
  5. SAPPHIRE: NCT03906071

Advanced or metastatic disease, subsequent lines of therapy

Note: this section includes regimens that were tested in second-line and beyond; those tested specifically in the second-line or third-line are to be found above.

Afatinib monotherapy

Regimen variant #1, 30 mg/day

FDA-recommended dose

Note: This is the FDA-recommended dose for patients with "severe renal impairment".

Targeted therapy

Continued indefinitely


Regimen variant #2, 50 mg/day

Study Years of enrollment Evidence Comparator Comparative Efficacy
Miller et al. 2012 (LUX-Lung 1) 2008-2009 Phase 3 (E-esc) Placebo Superior PFS
Katakami et al. 2013 (LUX-Lung 4) 2009-2011 Phase 2 ORR: 8% (95% CI: 3-18)

In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants, who had progressed while receiving erlotinib and/or gefitinib and had received one or two previous lines of chemotherapy, including at least one platinum-based regimen.

Targeted therapy

Continued indefinitely

References

  1. LUX-Lung 1: Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. link to original article contains dosing details in manuscript PubMed NCT00656136
    1. HRQoL analysis: Hirsh V, Cadranel J, Cong XJ, Fairclough D, Finnern HW, Lorence RM, Miller VA, Palmer M, Yang JC. Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1). J Thorac Oncol. 2013 Feb;8(2):229-37. link to original article PubMed
  2. LUX-Lung 4: Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. link to original article contains dosing details in manuscript PubMed NCT00711594

Afatinib & Paclitaxel

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Schuler et al. 2015 (LUX-Lung 5) 2010-2011 Phase 3 (E-esc) Single-agent chemotherapy Superior PFS

Targeted therapy

Chemotherapy

28-day cycles

References

  1. LUX-Lung 5: Schuler M, Yang JC, Park K, Kim JH, Bennouna J, Chen YM, Chouaid C, De Marinis F, Feng JF, Grossi F, Kim DW, Liu X, Lu S, Strausz J, Vinnyk Y, Wiewrodt R, Zhou C, Wang B, Chand VK, Planchard D; LUX-Lung 5 Investigators. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol. 2016 Mar;27(3):417-23. Epub 2015 Dec 8. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01085136

Amrubicin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Yoshioka et al. 2017 (D0702035) 2010-2012 Phase 3 (E-switch-ic) Docetaxel Did not meet primary endpoint of PFS

Chemotherapy

21-day cycles

References

  1. D0702035: Yoshioka H, Katakami N, Okamoto H, Iwamoto Y, Seto T, Takahashi T, Sunaga N, Kudoh S, Chikamori K, Harada M, Tanaka H, Saito H, Saka H, Takeda K, Nogami N, Masuda N, Harada T, Kitagawa H, Horio H, Yamanaka T, Fukuoka M, Yamamoto N, Nakagawa K. A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer. Ann Oncol. 2017 Feb 1;28(2):285-291. link to original article contains dosing details in manuscript PubMed NCT01207011

Atezolizumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fehrenbacher et al. 2016 (POPLAR) 2013-2014 Randomized Phase 2 (E-switch-ooc) Docetaxel Seems to have superior OS
Median OS: 12.6 vs 9.7 mo
(HR 0.73, 95% CI 0.53-0.99)
Rittmeyer et al. 2016 (OAK) 2014-2015 Phase 3 (E-RT-switch-ooc) Docetaxel Superior OS1
Median OS: 13.8 vs 9.6 mo
(HR 0.75, 95% CI 0.64-0.89)

1Reported efficacy is based on the 2018 update for the primary efficacy group.

Prior treatment criteria

Immunotherapy

21-day cycles

References

  1. POPLAR: Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. link to original article contains dosing details in abstract PubMed NCT01903993
  2. OAK: Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. Epub 2016 Dec 13. link to original article PubMed NCT02008227
    1. Update: Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, Han JY, Gadgeel SM, Hida T, Cortinovis DL, Cobo M, Kowalski DM, De Marinis F, Gandhi M, Danner B, Matheny C, Kowanetz M, He P, Felizzi F, Patel H, Sandler A, Ballinger M, Barlesi F. Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Aug;13(8):1156-1170. Epub 2018 May 17. Erratum in: J Thorac Oncol. 2018 Nov;13(11):1800. link to original article PubMed
    2. Update: von Pawel J, Bordoni R, Satouchi M, Fehrenbacher L, Cobo M, Han JY, Hida T, Moro-Sibilot D, Conkling P, Gandara DR, Rittmeyer A, Gandhi M, Yu W, Matheny C, Patel H, Sandler A, Ballinger M, Kowanetz M, Park K. Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. Eur J Cancer. 2019 Jan;107:124-132. Epub 2018 Dec 17. link to original article PubMed

Docetaxel monotherapy

Example orders

Regimen variant #1, 35 mg/m2, 3 out of 4 weeks

Study Years of enrollment Evidence Comparator Comparative Efficacy
Chen et al. 2006 2002-2004 Phase 3 (E-switch-ic) 1. Docetaxel; 40 mg/m2, 2 out of 3 wks Did not meet efficacy endpoint
2. Docetaxel; 75 mg/m2, every 3 wks Did not meet efficacy endpoint

Chemotherapy

Supportive therapy

28-day cycles


Regimen variant #2, 60 mg/m2 q3wk, indefinite

Study Years of enrollment Evidence Comparator Comparative Efficacy
Maruyama et al. 2008 (V-15-32) 2003-2006 Phase 3 (C) Gefitinib Inconclusive whether non-inferior OS
Kawaguchi et al. 2014 (DELTANSCLC) 2009-2012 Phase 3 (C) Erlotinib Might have superior PFS
Yoshioka et al. 2017 (D0702035) 2010-2012 Phase 3 (C) Amrubicin Did not meet primary endpoint of PFS
Nokihara et al. 2017 (EAST-LC) 2010-2014 Phase 3 (C) S-1 Non-inferior OS
Yoneshima et al. 2021 (J-AXEL) 2015-2018 Phase 3 (C) nab-Paclitaxel Non-inferior OS

Note: This is the PMDA-approved dose, the dose used for East Asian patients in REVEL, and the dose used in Japanese patients in EAST-LC.

Chemotherapy

21-day cycles


Regimen variant #3, 75 mg/m2 q3wk, indefinite

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shepherd et al. 2000 (TAX 317) 1994-1998 Phase 3 (E-RT-esc) Best supportive care Seems to have superior OS
Fossella et al. 2000 (TAX 320) 1995-1998 Phase 3 (E-RT-switch-ic) 1. Docetaxel; 100 mg/m2 Did not meet primary endpoint of OS
2. Ifosfamide
3. Vinorelbine 		Did not meet primary endpoint of OS
Camps et al. 2005 2000-2003 Phase 3 (C) Docetaxel; 36 mg/m2, 6 out of 8 wks Might have superior OS
Hanna et al. 2004 (JMEI) 2001-2002 Phase 3 (C) Pemetrexed Inconclusive whether non-inferior OS
Ramlau et al. 2006 (GSK 104864-A/387) 2001-2003 Phase 3 (C) Topotecan Might have superior OS
Chen et al. 2006 2002-2004 Phase 3 (C) 1. Docetaxel; 35 mg/m2, 3 out of 4 wks Did not meet efficacy endpoint
2. Docetaxel; 40 mg/m2, 2 out of 3 wks Did not meet efficacy endpoint
Fidias et al. 2008 2002-2005 Phase 3 (C) Docetaxel consolidation Might have inferior OS
Kim et al. 2008 (INTEREST) 2004-2006 Phase 3 (C) Gefitinib Seems to have non-inferior OS
Lee et al. 2010 (ISTANA) 2005-2006 Phase 3 (C) Gefitinib Seems to have inferior PFS
Ramlau et al. 2012 (EFC10261) 2007-2010 (C) Phase 3 (C) Docetaxel & Ziv-aflibercept Did not meet primary endpoint of OS
Median OS: 10.4 vs 10.1 mo
(HR 0.99, 95% CI 0.85-1.15)
Reck et al. 2014 (LUME-Lung 1) 2008-2011 Phase 3 (C) Docetaxel & Nintedanib Inferior PFS
Nokihara et al. 2017 (EAST-LC) 2010-2014 Phase 3 (C) S-1 Non-inferior OS
Katakami et al. 2017 (E7389-G000-302) 2011-2014 (C) Phase 3 (C) Eribulin Might have superior OS
Median OS: 9.5 vs 9.5 mo
(HR 0.86, 95% CI 0.71-1.05)
Fehrenbacher et al. 2016 (POPLAR) 2013-2014 Randomized Phase 2 (C) Atezolizumab Seems to have inferior OS
Herbst et al. 2015 (KEYNOTE-010) 2013-2015 Phase 2/3 (C) 1. Pembrolizumab; 2 mg/kg
2. Pembrolizumab; 10 mg/kg 		Inferior OS
Rittmeyer et al. 2016 (OAK) 2014-2015 Phase 3 (C) Atezolizumab Inferior OS
Wu et al. 2019 (CheckMate 078) 2015-2016 Phase 3 (C) Nivolumab Inferior OS
Barlesi et al. 2018 (JAVELIN Lung 200) 2015-2017 Phase 3 (C) Avelumab Did not meet primary endpoint of OS
Awaiting publication (KN046-302) 2021-2024 Phase 3 (C) 1. Lenvatinib
2. Lenvatinib & KN046 		TBD

Prior treatment criteria

Chemotherapy

Supportive therapy

21-day cycles


Regimen variant #4, 100 mg/m2 q3wk

Study Evidence
Fossella et al. 1995 Phase 2

Chemotherapy

21-day cycles

References

  1. Fossella FV, Lee JS, Shin DM, Calayag M, Huber M, Perez-Soler R, Murphy WK, Lippman S, Benner S, Glisson B, Chasen M, Hong WK, Raber M. Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer. J Clin Oncol. 1995 Mar;13(3):645-51. link to original article contains dosing details in abstract PubMed
  2. TAX 317: Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O'Rourke M, Levitan N, Gressot L, Vincent M, Burkes R, Coughlin S, Kim Y, Berille J. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol. 2000 May;18(10):2095-103. link to original article contains dosing details in abstract PubMed
  3. TAX 320: Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L; TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209. link to original article contains dosing details in manuscript PubMed
  4. JMEI: Hanna N, Shepherd FA, Fossella FV, Rodrigues Pereira J, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar M, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. link to original article contains dosing details in manuscript PubMed
  5. Camps C, Massuti B, Jiménez A, Maestu I, Gómez RG, Isla D, González JL, Almenar D, Blasco A, Rosell R, Carrato A, Viñolas N, Batista N, Girón CG, Galán A, López M, Blanco R, Provencio M, Diz P, Felip E; Spanish Lung Cancer Group. Randomized phase III study of 3-weekly versus weekly docetaxel in pretreated advanced non-small-cell lung cancer: a Spanish Lung Cancer Group trial. Ann Oncol. 2006 Mar;17(3):467-72. Epub 2005 Dec 21. link to original article contains dosing details in abstract PubMed
  6. Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest. 2006 Apr;129(4):1031-8. link to original article contains dosing details in manuscript PubMed
  7. GSK 104864-A/387: Ramlau R, Gervais R, Krzakowski M, von Pawel J, Kaukel E, Abratt RP, Dharan B, Grotzinger KM, Ross G, Dane G, Shepherd FA. Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. J Clin Oncol. 2006 Jun 20;24(18):2800-7. Epub 2006 May 8. link to original article contains dosing details in abstract PubMed NCT00049998
  8. V-15-32: Maruyama R, Nishiwaki Y, Tamura T, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Inoue A, Tomii K, Harada M, Masuda N, Jiang H, Itoh Y, Ichinose Y, Saijo N, Fukuoka M. Phase III study, V-15-32, of gefitinib versus docetaxel in previously treated Japanese patients with non-small-cell lung cancer. J Clin Oncol. 2008 Sep 10;26(26):4244-52. link to original article contains dosing details in manuscript PubMed NCT00252707
    1. HRQoL analysis: Sekine I, Ichinose Y, Nishiwaki Y, Yamamoto N, Tsuboi M, Nakagawa K, Shinkai T, Negoro S, Imamura F, Eguchi K, Takeda K, Itoh Y, Tamura T, Saijo N, Fukuoka M. Quality of life and disease-related symptoms in previously treated Japanese patients with non-small-cell lung cancer: results of a randomized phase III study (V-15-32) of gefitinib versus docetaxel. Ann Oncol. 2009 Sep;20(9):1483-8. Epub 2009 Mar 12. link to original article PubMed
  9. INTEREST: Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. link to original article contains dosing details in abstract PubMed NCT00076388
    1. Dataset: Project Data Sphere
  10. Fidias PM, Dakhil SR, Lyss AP, Loesch DM, Waterhouse DM, Bromund JL, Chen R, Hristova-Kazmierski M, Treat J, Obasaju CK, Marciniak M, Gill J, Schiller JH. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Feb 1;27(4):591-8. Epub 2008 Dec 15. link to original articlecontains dosing details in manuscript PubMed
  11. ISTANA: Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW. Randomized phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010 Feb 15;16(4):1307-14. Epub 2010 Feb 9. link to original article contains dosing details in abstract PubMed NCT00478049
  12. EFC10261: Ramlau R, Gorbunova V, Ciuleanu TE, Novello S, Ozguroglu M, Goksel T, Baldotto C, Bennouna J, Shepherd FA, Le-Guennec S, Rey A, Miller V, Thatcher N, Scagliotti G. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012 Oct 10;30(29):3640-7. Epub 2012 Sep 10. link to original article contains dosing details in abstract PubMed NCT00532155
    1. Dataset: Project Data Sphere
  13. LUME-Lung 1: Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. link to original article contains dosing details in abstract PubMed NCT00805194
  14. KEYNOTE-010: Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. link to original article contains dosing details in abstract PubMed NCT01905657
    1. Update: Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020 May 10;38(14):1580-1590. Epub 2020 Feb 20. link to original article PubMed
  15. POPLAR: Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. link to original article contains dosing details in abstract PubMed NCT01903993
  16. OAK: Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC, Cortinovis DL, Leach J, Polikoff J, Barrios C, Kabbinavar F, Frontera OA, De Marinis F, Turna H, Lee JS, Ballinger M, Kowanetz M, He P, Chen DS, Sandler A, Gandara DR; OAK Study Group. Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet. 2017 Jan 21;389(10066):255-265. Epub 2016 Dec 13. link to original article contains dosing details in abstract PubMed NCT02008227
    1. Update: Fehrenbacher L, von Pawel J, Park K, Rittmeyer A, Gandara DR, Ponce Aix S, Han JY, Gadgeel SM, Hida T, Cortinovis DL, Cobo M, Kowalski DM, De Marinis F, Gandhi M, Danner B, Matheny C, Kowanetz M, He P, Felizzi F, Patel H, Sandler A, Ballinger M, Barlesi F. Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2018 Aug;13(8):1156-1170. Epub 2018 May 17. Erratum in: J Thorac Oncol. 2018 Nov;13(11):1800. link to original article PubMed
    2. Update: von Pawel J, Bordoni R, Satouchi M, Fehrenbacher L, Cobo M, Han JY, Hida T, Moro-Sibilot D, Conkling P, Gandara DR, Rittmeyer A, Gandhi M, Yu W, Matheny C, Patel H, Sandler A, Ballinger M, Kowanetz M, Park K. Long-term survival in patients with advanced non-small-cell lung cancer treated with atezolizumab versus docetaxel: Results from the randomised phase III OAK study. Eur J Cancer. 2019 Jan;107:124-132. Epub 2018 Dec 17. link to original article PubMed
  17. D0702035: Yoshioka H, Katakami N, Okamoto H, Iwamoto Y, Seto T, Takahashi T, Sunaga N, Kudoh S, Chikamori K, Harada M, Tanaka H, Saito H, Saka H, Takeda K, Nogami N, Masuda N, Harada T, Kitagawa H, Horio H, Yamanaka T, Fukuoka M, Yamamoto N, Nakagawa K. A randomized, open-label, phase III trial comparing amrubicin versus docetaxel in patients with previously treated non-small-cell lung cancer. Ann Oncol. 2017 Feb 1;28(2):285-291. link to original article contains dosing details in manuscript PubMed NCT01207011
  18. E7389-G000-302: Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01454934
  19. EAST-LC: Nokihara H, Lu S, Mok TSK, Nakagawa K, Yamamoto N, Shi YK, Zhang L, Soo RA, Yang JC, Sugawara S, Nishio M, Takahashi T, Goto K, Chang J, Maemondo M, Ichinose Y, Cheng Y, Lim WT, Morita S, Tamura T. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol. 2017 Nov 1;28(11):2698-2706. link to original article link to PMC article contains dosing details in manuscript PubMed JapicCTI-101155
  20. JAVELIN Lung 200: Barlesi F, Vansteenkiste J, Spigel D, Ishii H, Garassino M, de Marinis F, Özgüroğlu M, Szczesna A, Polychronis A, Uslu R, Krzakowski M, Lee JS, Calabrò L, Arén Frontera O, Ellers-Lenz B, Bajars M, Ruisi M, Park K. Avelumab versus docetaxel in patients with platinum-treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomised, phase 3 study. Lancet Oncol. 2018 Nov;19(11):1468-79. Epub 2018 Sep 21. link to original article contains dosing details in abstract PubMed NCT02395172
    1. Update: Park K, Özgüroğlu M, Vansteenkiste J, Spigel D, Yang JCH, Ishii H, Garassino M, de Marinis F, Szczesna A, Polychronis A, Uslu R, Krzakowski M, Lee JS, Calabrò L, Arén Frontera O, Xiong H, Bajars M, Ruisi M, Barlesi F. Avelumab Versus Docetaxel in Patients With Platinum-Treated Advanced NSCLC: 2-Year Follow-Up From the JAVELIN Lung 200 Phase 3 Trial. J Thorac Oncol. 2021 Aug;16(8):1369-1378. Epub 2021 Apr 9. link to original article PubMed
  21. CheckMate 078: Wu YL, Lu S, Cheng Y, Zhou C, Wang J, Mok T, Zhang L, Tu HY, Wu L, Feng J, Zhang Y, Luft AV, Zhou J, Ma Z, Lu Y, Hu C, Shi Y, Baudelet C, Cai J, Chang J. Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial. J Thorac Oncol. 2019 May;14(5):867-875. Epub 2019 Jan 17. link to original article contains dosing details in abstract PubMed NCT02613507
    1. Update: Lu S, Wang J, Cheng Y, Mok T, Chang J, Zhang L, Feng J, Tu HY, Wu L, Zhang Y, Luft A, Zhou JY, Ma Z, Lu Y, Hu C, Shi Y, Ying K, Zhong H, Poddubskaya E, Soo RA, Chia YH, Li A, Li A, Wu YL. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078). Lung Cancer. 2021 Feb;152:7-14. Epub 2020 Nov 24. link to original article PubMed
  22. J-AXEL: Yoneshima Y, Morita S, Ando M, Nakamura A, Iwasawa S, Yoshioka H, Goto Y, Takeshita M, Harada T, Hirano K, Oguri T, Kondo M, Miura S, Hosomi Y, Kato T, Kubo T, Kishimoto J, Yamamoto N, Nakanishi Y, Okamoto I. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol. 2021 Sep;16(9):1523-1532. Epub 2021 Apr 27. link to original article contains dosing details in manuscript PubMed
  23. KN046-302: NCT05001724

Docetaxel & Nintedanib

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Reck et al. 2014 (LUME-Lung 1) 2008-2011 Phase 3 (E-esc) Docetaxel Superior PFS

Chemotherapy

Targeted therapy

21-day cycles

References

  1. LUME-Lung 1: Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. link to original article contains dosing details in abstract PubMed NCT00805194

Gefitinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Kris et al. 2003 (IDEAL2) 2000-2001 Randomized Phase 2 (E-RT-de-esc) Gefitinib; 500 mg/day Did not meet primary endpoint of ORR
Thatcher et al. 2005 (ISEL) NR Phase 3 (E-esc) Placebo Might have superior OS
Kim et al. 2008 (INTEREST) 2004-2006 Phase 3 (E-switch-ooc) Docetaxel Seems to have non-inferior OS
Lee et al. 2010 (ISTANA) 2005-2006 Phase 3 (E-switch-ooc) Docetaxel Seems to have superior PFS
Han et al. 2011 (NCCCTS-06-177) 2006-2008 Randomized Phase 2 (C) Gefitinib & Simvastatin Did not meet primary endpoint of ORR
Shi et al. 2013 (ICOGEN) 2009 Phase 3 (C) Icotinib Seems to have non-inferior PFS

Note: IDEAL2 was the basis of initial FDA approval in 2003.

Targeted therapy

Continued indefinitely

References

  1. IDEAL2: Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. link to original article PubMed
  2. ISEL: Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, Carroll K. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37. link to original article PubMed NCT00242801
  3. INTEREST: Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. link to original article contains dosing details in manuscript PubMed NCT00076388
    1. Dataset: Project Data Sphere
  4. ISTANA: Lee DH, Park K, Kim JH, Lee JS, Shin SW, Kang JH, Ahn MJ, Ahn JS, Suh C, Kim SW. Randomized phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy. Clin Cancer Res. 2010 Feb 15;16(4):1307-14. Epub 2010 Feb 9. link to original article contains dosing details in abstract PubMed NCT00478049
  5. NCCCTS-06-177: Han JY, Lee SH, Yoo NJ, Hyung LS, Moon YJ, Yun T, Kim HT, Lee JS. A randomized phase II study of gefitinib plus simvastatin versus gefitinib alone in previously treated patients with advanced non-small cell lung cancer. Clin Cancer Res. 2011 Mar 15;17(6):1553-60. link to orinigal article contains dosing details in abstract PubMed NCT00452244
  6. ICOGEN: Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. link to original article PubMed NCT01040780

Gemcitabine monotherapy

Regimen variant #1, 1000 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Katakami et al. 2017 (E7389-G000-302) 2011-2014 (C) Phase 3 (C) Eribulin Might have superior OS
Median OS: 9.5 vs 9.5 mo
(HR 0.86, 95% CI 0.71-1.05)
Planchard et al. 2020 (ARCTIC) 2015-2016 Phase 3 (C) 1. Durvalumab & Tremelimumab Might have inferior PFS
2. Durvalumab
3. Tremelimumab 		Not reported

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

28-day cycles


Regimen variant #2, 1250 mg/m2

Study Years of enrollment Evidence Comparator Comparative Efficacy
Katakami et al. 2017 (E7389-G000-302) 2011-2014 (C) Phase 3 (C) Eribulin Might have superior OS
Median OS: 9.5 vs 9.5 mo
(HR 0.86, 95% CI 0.71-1.05)

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

21-day cycles

References

  1. E7389-G000-302: Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01454934
  2. ARCTIC: Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. Epub 2020 Feb 20. link to original article contains dosing details in supplement PubMed NCT02352948

Icotinib monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shi et al. 2013 (ICOGEN) 2009 Phase 3 (E-switch-ic) Gefitinib Seems to have non-inferior PFS

Note: this drug is only approved in China.

Targeted therapy

Continued indefinitely

References

  1. ICOGEN: Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. link to original article contains dosing details in abstract PubMed NCT01040780

Nivolumab monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wu et al. 2019 (CheckMate 078) 2015-2016 Phase 3 (E-switch-ooc) Docetaxel Superior OS1
Median OS: 11.9 vs 9.5 mo
(HR 0.75, 95% CI 0.61-0.93)

1Reported efficacy is based on the 2020 update.

Prior treatment criteria

Immunotherapy

  • Nivolumab (Opdivo) 3 mg/kg IV once on day 1
    • Notably, on 9/13/16 the FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.

14-day cycles

References

  1. CheckMate 078: Wu YL, Lu S, Cheng Y, Zhou C, Wang J, Mok T, Zhang L, Tu HY, Wu L, Feng J, Zhang Y, Luft AV, Zhou J, Ma Z, Lu Y, Hu C, Shi Y, Baudelet C, Cai J, Chang J. Nivolumab Versus Docetaxel in a Predominantly Chinese Patient Population With Previously Treated Advanced NSCLC: CheckMate 078 Randomized Phase III Clinical Trial. J Thorac Oncol. 2019 May;14(5):867-875. Epub 2019 Jan 17. link to original article contains dosing details in abstract PubMed NCT02613507
    1. Update: Lu S, Wang J, Cheng Y, Mok T, Chang J, Zhang L, Feng J, Tu HY, Wu L, Zhang Y, Luft A, Zhou JY, Ma Z, Lu Y, Hu C, Shi Y, Ying K, Zhong H, Poddubskaya E, Soo RA, Chia YH, Li A, Li A, Wu YL. Nivolumab versus docetaxel in a predominantly Chinese patient population with previously treated advanced non-small cell lung cancer: 2-year follow-up from a randomized, open-label, phase 3 study (CheckMate 078). Lung Cancer. 2021 Feb;152:7-14. Epub 2020 Nov 24. link to original article PubMed

nab-Paclitaxel monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Yoneshima et al. 2021 (J-AXEL) 2015-2018 Phase 3 (E-switch-ic) Docetaxel Non-inferior OS

Chemotherapy

21-day cycles

References

  1. J-AXEL: Yoneshima Y, Morita S, Ando M, Nakamura A, Iwasawa S, Yoshioka H, Goto Y, Takeshita M, Harada T, Hirano K, Oguri T, Kondo M, Miura S, Hosomi Y, Kato T, Kubo T, Kishimoto J, Yamamoto N, Nakanishi Y, Okamoto I. Phase 3 Trial Comparing Nanoparticle Albumin-Bound Paclitaxel With Docetaxel for Previously Treated Advanced NSCLC. J Thorac Oncol. 2021 Sep;16(9):1523-1532. Epub 2021 Apr 27. link to original article contains dosing details in manuscript PubMed

Pembrolizumab monotherapy

Regimen variant #1, 2 mg/kg

Study Years of enrollment Evidence Comparator Comparative Efficacy
Garon et al. 2015 (KEYNOTE-001) 2012-2014 Phase 1, >20 pts in dosing cohort
Herbst et al. 2015 (KEYNOTE-010) 2013-2015 Phase 2/3 (E-RT-switch-ooc) 1. Docetaxel Superior OS
Median OS: 10.4 vs 8.5 mo
(HR 0.71, 95% CI 0.58-0.88)
2. Pembrolizumab; 10 mg/kg Not reported

Note: patients had previously received chemotherapy.

Immunotherapy

21-day cycles


Regimen variant #2, 10 mg/kg

Study Years of enrollment Evidence Comparator Comparative Efficacy
Garon et al. 2015 (KEYNOTE-001) 2012-2014 Phase 1, >20 pts in dosing cohort
Herbst et al. 2015 (KEYNOTE-010) 2013-2015 Phase 2/3 (E-RT-switch-ooc) 1. Docetaxel Superior OS
Median OS: 12.7 vs 8.5 mo
(HR 0.61, 95% CI 0.49-0.75)
2. Pembrolizumab; 2 mg/kg Not reported

Note: patients had previously received chemotherapy.

Immunotherapy

21-day cycles

References

  1. KEYNOTE-001: Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. link to original article PubMed NCT01295827
  2. KEYNOTE-010: Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. link to original article contains dosing details in abstract PubMed NCT01905657
    1. Update: Herbst RS, Garon EB, Kim DW, Cho BC, Perez-Gracia JL, Han JY, Arvis CD, Majem M, Forster MD, Monnet I, Novello S, Szalai Z, Gubens MA, Su WC, Ceresoli GL, Samkari A, Jensen EH, Lubiniecki GM, Baas P. Long-Term Outcomes and Retreatment Among Patients With Previously Treated, Programmed Death-Ligand 1‒Positive, Advanced Non‒Small-Cell Lung Cancer in the KEYNOTE-010 Study. J Clin Oncol. 2020 May 10;38(14):1580-1590. Epub 2020 Feb 20. link to original article PubMed

Pemetrexed monotherapy

Example orders

Regimen

FDA-recommended dose
Study Years of enrollment Evidence Comparator Comparative Efficacy
Hanna et al. 2004 (JMEI) 2001-2002 Phase 3 (E-RT-switch-ic) Docetaxel Inconclusive whether non-inferior OS
Kim et al. 2013 (JXBC) 2005-2010 Phase 3 (C) Pemetrexed & Cetuximab Did not meet primary endpoint of PFS
Median PFS: 2.8 vs 2.9 mo
(HR 0.97, 95% CI 0.83-1.15)
Karampeazis et al. 2013 (CT/06.05) 2006-2010 Phase 3 (E-switch-ooc) Erlotinib Did not meet primary endpoint of TTP
Katakami et al. 2017 (E7389-G000-302) 2011-2014 (C) Phase 3 (C) Eribulin Might have superior OS
Median OS: 9.5 vs 9.5 mo
(HR 0.86, 95% CI 0.71-1.05)

Note: JXBC also evaluated docetaxel versus docetaxel & cetuximab, but did not report the efficacy of this comparison; see paper for details.

Chemotherapy

Supportive therapy

21-day cycles

References

  1. JMEI: Hanna N, Shepherd FA, Fossella FV, Rodrigues Pereira J, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar M, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. link to original article contains dosing details in abstract PubMed
  2. CT/06.05: Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. link to original article contains dosing details in manuscript PubMed NCT00440414
  3. JXBC: Kim ES, Neubauer M, Cohn A, Schwartzberg L, Garbo L, Caton J, Robert F, Reynolds C, Katz T, Chittoor S, Simms L, Saxman S. Docetaxel or pemetrexed with or without cetuximab in recurrent or progressive non-small-cell lung cancer after platinum-based therapy: a phase 3, open-label, randomised trial. Lancet Oncol. 2013 Dec;14(13):1326-36. Epub 2013 Nov 12. Erratum in: Lancet Oncol. 2014 Jan;15(1):e4. link to original article contains dosing details in abstract PubMed NCT00095199
  4. E7389-G000-302: Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01454934

S-1 monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Nokihara et al. 2017 (EAST-LC) 2010-2014 Phase 3 (E-switch-ic) Docetaxel Non-inferior OS

Chemotherapy

  • Tegafur, gimeracil, oteracil (S-1) by the following criteria:
    • BSA less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
    • BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 28
    • BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 28

42-day cycles

References

  1. EAST-LC: Nokihara H, Lu S, Mok TSK, Nakagawa K, Yamamoto N, Shi YK, Zhang L, Soo RA, Yang JC, Sugawara S, Nishio M, Takahashi T, Goto K, Chang J, Maemondo M, Ichinose Y, Cheng Y, Lim WT, Morita S, Tamura T. Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer). Ann Oncol. 2017 Nov 1;28(11):2698-2706. link to original article link to PMC article PubMed JapicCTI-101155

Vinorelbine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Fossella et al. 2000 (TAX 320) 1995-1998 Phase 3 (C) 1. Docetaxel 100 mg/m2 Did not meet primary endpoint of OS
2. Docetaxel 75 mg/m2 Did not meet primary endpoint of OS
Katakami et al. 2017 (E7389-G000-302) 2011-2014 (C) Phase 3 (C) Eribulin Might have superior OS
Median OS: 9.5 vs 9.5 mo
(HR 0.86, 95% CI 0.71-1.05)
Planchard et al. 2020 (ARCTIC) 2015-2016 Phase 3 (C) 1. [[#Durvalumab_.26_Tremelimumab_77|Durvalumab & Tremelimumab Might have inferior PFS
2. Durvalumab
3. Tremelimumab 		Not reported

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Chemotherapy

Supportive therapy

  • Per TAX 320:
  • Patients who had either grade 4 neutropenia lasting at least 5 days or both fever and grade 3 or 4 neutropenia could receive G-CSF (dose/schedule/duration not specified)
  • Metoclopramide (Reglan) (dose/schedule/route not specified) used first for nausea
  • Nausea despite metoclopramide was treated with a 5-HT3 antagonist such as Ondansetron (Zofran) or Granisetron (dose/schedule/route not specified) prn nausea

28-day cycles

References

  1. TAX 320: Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, Kalman L, Miller V, Lee JS, Moore M, Gandara D, Karp D, Vokes E, Kris M, Kim Y, Gamza F, Hammershaimb L; TAX 320 Non-Small Cell Lung Cancer Study Group. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol. 2000 Jun;18(12):2354-62. Erratum in: J Clin Oncol. 2004 Jan 1;22(1):209. link to original article contains dosing details in manuscript PubMed
  2. E7389-G000-302: Katakami N, Felip E, Spigel DR, Kim JH, Olivo M, Guo M, Nokihara H, Yang JC, Iannotti N, Satouchi M, Barlesi F. A randomized, open-label, multicenter, phase 3 study to compare the efficacy and safety of eribulin to treatment of physician's choice in patients with advanced non-small cell lung cancer. Ann Oncol. 2017 Sep 1;28(9):2241-2247. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01454934
  3. ARCTIC: Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. Epub 2020 Feb 20. link to original article contains dosing details in supplement PubMed NCT02352948

CNS metastases, all lines of therapy

Dexamethasone monotherapy

Regimen

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
Mulvenna et al. 2016 (QUARTZ) Phase 3 (E-de-esc) Dexamethasone & WBRT Inconclusive whether non-inferior QALYs

Supportive therapy

References

  1. QUARTZ: Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. link to original article link to PMC article PubMed ISRCTN3826061

Dexamethasone & WBRT

Regimen

Study Evidence Comparator Comparative Efficacy Comparative Toxicity
Mulvenna et al. 2016 (QUARTZ) Phase 3 (C) Dexamethasone Inconclusive whether non-inferior QALYs

Radiotherapy

  • WBRT, 20 Gy in 5 fractions

Supportive therapy

References

  1. QUARTZ: Mulvenna P, Nankivell M, Barton R, Faivre-Finn C, Wilson P, McColl E, Moore B, Brisbane I, Ardron D, Holt T, Morgan S, Lee C, Waite K, Bayman N, Pugh C, Sydes B, Stephens R, Parmar MK, Langley RE. Dexamethasone and supportive care with or without whole brain radiotherapy in treating patients with non-small cell lung cancer with brain metastases unsuitable for resection or stereotactic radiotherapy (QUARTZ): results from a phase 3, non-inferiority, randomised trial. Lancet. 2016 Oct 22;388(10055):2004-2014. Epub 2016 Sep 4. link to original article link to PMC article PubMed ISRCTN3826061

Teniposide & WBRT

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Postmus et al. 2000 1989-1995 Phase 3 (E-esc) Teniposide Might have superior OS

Chemotherapy

Radiotherapy

  • WBRT, 30 Gy in 10 fractions

References

  1. Postmus PE, Haaxma-Reiche H, Smit EF, Groen HJ, Karnicka H, Lewinski T, van Meerbeeck J, Clerico M, Gregor A, Curran D, Sahmoud T, Kirkpatrick A, Giaccone G; European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. Treatment of brain metastases of small-cell lung cancer: comparing teniposide and teniposide with whole-brain radiotherapy--a phase III study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol. 2000 Oct 1;18(19):3400-8. link to original article PubMed

Investigational agents

Drugs with some degree of promising activity in clinical trials.

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