Difference between revisions of "Non-small cell lung cancer, EGFR-mutated"
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− | {{#lst: | + | <span id="BackToTop"></span> |
+ | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | ||
+ | [[#top|Back to Top]] | ||
+ | </div> | ||
+ | {{#lst:Editorial board transclusions|nsclc}} | ||
Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens. | Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens. | ||
+ | <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]]''' | ||
+ | *'''Site-specific:''' | ||
+ | **'''[[Non-small cell lung cancer, CNS metastases|NSCLC, CNS metastases]]''' | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
Line 8: | Line 18: | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==[https://www.asco.org/ ASCO]== | ||
+ | *'''2023:''' Jaiyesimi et al. [https://doi.org/10.1200/jco.22.02782 Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.3] [https://pubmed.ncbi.nlm.nih.gov/36802359/ PubMed] | ||
+ | **'''2022:''' Singh et al. [https://doi.org/10.1200/jco.22.00824 Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline] [https://pubmed.ncbi.nlm.nih.gov/35816666 PubMed] | ||
+ | |||
+ | ==[https://www.esmo.org/ ESMO]== | ||
+ | *'''2023:''' Hendriks et al. [https://doi.org/10.1016/j.annonc.2022.12.009 Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/36872130 PubMed] | ||
+ | *'''2022:''' Passaro et al. [https://doi.org/10.1016/j.annonc.2022.02.003 ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer] [https://pubmed.ncbi.nlm.nih.gov/35176458 PubMed] | ||
+ | |||
==IASLC== | ==IASLC== | ||
+ | *'''2016:''' Tan et al. [https://doi.org/10.1016/j.jtho.2016.05.008 The International Association for the Study of Lung Cancer consensus statement on optimizing management of EGFR mutation–positive non–small cell lung cancer: Status in 2016] [https://pubmed.ncbi.nlm.nih.gov/27229180/ PubMed] | ||
+ | |||
+ | ==NCCN== | ||
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1450 NCCN Guidelines - Non-Small Cell Lung Cancer].'' | ||
+ | |||
+ | =Neoadjuvant therapy= | ||
+ | ==Carboplatin & Pemetrexed {{#subobject:1y66b4|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:10it3q|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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.clinicaltrials.gov/study/NCT04351555 Awaiting publication (NeoADAURA)] | ||
+ | |2020-ongoing | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Osimertinib.2C_Pemetrexed_666|Pem-Carbo & Osimertinib]]<br>1b. [[#Cisplatin.2C_Osimertinib.2C_Pemetrexed_666|Pem-Cis & Osimertinib]]<br>2. [[#Osimertinib_monotherapy_666|Osimertinib]] | ||
+ | | style="background-color:#d3d3d3" |TBD if different primary endpoint of major pathological response | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | ||
+ | *[[Pemetrexed (Alimta)]] 500 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#Lung_cancer_surgery|Surgical resection]] | ||
+ | </div></div> | ||
− | + | ===References=== | |
+ | #'''NeoADAURA:''' [https://clinicaltrials.gov/study/NCT04351555 NCT04351555] | ||
− | = | + | ==Cisplatin & Pemetrexed {{#subobject:13rjb4|Regimen=1}}== |
− | == | + | Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin |
− | {| class="wikitable" style=" | + | <br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8fdt3q|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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.clinicaltrials.gov/study/NCT04351555 Awaiting publication (NeoADAURA)] | ||
+ | |2020-ongoing | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Osimertinib.2C_Pemetrexed_666|Pem-Carbo & Osimertinib]]<br>1b. [[#Cisplatin.2C_Osimertinib.2C_Pemetrexed_666|Pem-Cis & Osimertinib]]<br>2. [[#Osimertinib_monotherapy_666|Osimertinib]] | ||
+ | | style="background-color:#d3d3d3" |TBD if different primary endpoint of major pathological response | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <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''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *[[Surgery#Lung_cancer_surgery|Surgical resection]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''NeoADAURA:''' [https://clinicaltrials.gov/study/NCT04351555 NCT04351555] | ||
+ | |||
+ | =Adjuvant therapy= | ||
+ | ==Cisplatin & Vinorelbine (CVb) {{#subobject:ab1b88|Regimen=1}}== | ||
CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine | CVb: '''<u>C</u>'''isplatin & '''<u>V</u>'''inorel'''<u>b</u>'''ine | ||
− | ===Regimen {{#subobject:04b3e6|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 75/25 {{#subobject:04b3e6|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(17)30729-5 Zhong et al. 2017 (ADJUVANT/CTONG1104)] |
|2011-2014 | |2011-2014 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 34: | Line 116: | ||
|- | |- | ||
|} | |} | ||
− | ====Biomarker | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | + | ====Biomarker eligibility criteria==== | |
− | * | + | *EGFR exon 19 deletion or EGFR p.L858R |
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks | *Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 6 to 12 weeks | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Vinorelbine (Navelbine)]] | + | *[[Vinorelbine (Navelbine)]] 25 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, 80/25 {{#subobject:iugvc6|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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.21.01729 Tada et al. 2021 (IMPACT<sub>NSCLC</sub>)] | ||
+ | |2011-2015 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Gefitinib_monotherapy|Gefinitib]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this trial should not be confused by those with the same name in prostate cancer and colon cancer.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or EGFR p.L858R | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Complete [[Surgery#Lung_cancer_surgery|surgical resection]], within 3 to 8 weeks | ||
+ | </div> | ||
+ | <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 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ADJUVANT/CTONG1104:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. [https://doi.org/10.1016/S1470-2045(17)30729-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29174310/ PubMed] [https://clinicaltrials.gov/study/NCT01405079 NCT01405079] | |
− | #'''ADJUVANT/CTONG1104:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. [https:// | + | ##'''Update:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.01820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078324/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33332190/ PubMed] |
− | ##'''Update:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.01820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33332190/ PubMed] | + | #'''IMPACT<sub>NSCLC</sub>:''' Tada H, Mitsudomi T, Misumi T, Sugio K, Tsuboi M, Okamoto I, Iwamoto Y, Sakakura N, Sugawara S, Atagi S, Takahashi T, Hayashi H, Okada M, Inokawa H, Yoshioka H, Takahashi K, Higashiyama M, Yoshino I, Nakagawa K; West Japan Oncology Group. Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT). J Clin Oncol. 2022 Jan 20;40(3):231-241. Epub 2021 Nov 2. [https://doi.org/10.1200/jco.21.01729 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34726958/ PubMed] UMIN000006252 |
− | |||
==Gefitinib monotherapy {{#subobject:4383b8|Regimen=1}}== | ==Gefitinib monotherapy {{#subobject:4383b8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:fc00be|Variant=1}}=== | ===Regimen {{#subobject:fc00be|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(17)30729-5 Zhong et al. 2017 (ADJUVANT/CTONG1104)] |
|2011-2014 | |2011-2014 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |[[#Cisplatin_. | + | |[[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]] |
− | | style="background-color:#1a9850" |Superior DFS<br>Median DFS: 28.7 vs 18 mo<br>(HR 0.60, 95% CI 0.42-0.87) | + | | style="background-color:#1a9850" |Superior DFS (primary endpoint)<br>Median DFS: 28.7 vs 18 mo<br>(HR 0.60, 95% CI 0.42-0.87) |
|- | |- | ||
|} | |} | ||
− | ====Biomarker | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | + | ====Biomarker eligibility criteria==== | |
*Biomarker: EGFR exon 19 deletion and exon 21 L858R activating mutations | *Biomarker: EGFR exon 19 deletion and exon 21 L858R activating mutations | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Lung_cancer_surgery|Surgery]] | *[[Surgery#Lung_cancer_surgery|Surgery]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Gefitinib (Iressa)]] 250 mg PO once per day | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
− | |||
'''24-month course''' | '''24-month course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ADJUVANT/CTONG1104:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. [https://doi.org/10.1016/S1470-2045(17)30729-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29174310/ PubMed] [https://clinicaltrials.gov/study/NCT01405079 NCT01405079] | |
− | #'''ADJUVANT/CTONG1104:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. [https:// | + | ##'''Update:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.01820 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078324/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33332190/ PubMed] |
− | ##'''Update:''' Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. [https://doi.org/10.1200/jco.20.01820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33332190/ PubMed] | ||
− | |||
==Icotinib monotherapy {{#subobject:9hgya1|Regimen=1}}== | ==Icotinib monotherapy {{#subobject:9hgya1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:zb81bb|Variant=1}}=== | ===Regimen {{#subobject:zb81bb|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 107: | Line 209: | ||
|- | |- | ||
|[https://doi.org/10.1016/s2213-2600(21)00134-x He et al. 2021 (EVIDENCE)] | |[https://doi.org/10.1016/s2213-2600(21)00134-x He et al. 2021 (EVIDENCE)] | ||
− | |2015-2019 | + | |2015-06-08 to 2019-08-02 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | | | + | |1a. [[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]]<br>1b. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|Cisplatin & Vinorelbine]] |
− | | style="background-color:#1a9850" |Superior DFS<br>Median DFS: 47 vs 22.1 mo<br>(HR 0.36, 95% CI 0.24-0.55) | + | | style="background-color:#1a9850" |Superior DFS (primary endpoint)<br>Median DFS: 47 vs 22.1 mo<br>(HR 0.36, 95% CI 0.24-0.55) |
|- | |- | ||
|} | |} | ||
''Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.'' | ''Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*EGFR exon 19 or 21 mutations | *EGFR exon 19 or 21 mutations | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
*[[Surgery#Lung_cancer_surgery|Complete resection]], within 8 weeks | *[[Surgery#Lung_cancer_surgery|Complete resection]], within 8 weeks | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Icotinib (Conmana)]] 125 mg PO three times per day | *[[Icotinib (Conmana)]] 125 mg PO three times per day | ||
− | |||
'''2-year course''' | '''2-year course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''EVIDENCE:''' He J, Su C, Liang W, Xu S, Wu L, Fu X, Zhang X, Ge D, Chen Q, Mao W, Xu L, Chen C, Hu B, Shao G, Hu J, Zhao J, Liu X, Liu Z, Wang Z, Xiao Z, Gong T, Lin W, Li X, Ye F, Liu Y, Ma H, Huang Y, Zhou J, Wang Z, Fu J, Ding L, Mao L, Zhou C. Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir Med. 2021 Sep;9(9):1021-1029. Epub 2021 Jul 21. [https://doi.org/10.1016/s2213-2600(21)00134-x link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34280355/ PubMed] [https://clinicaltrials.gov/study/NCT02448797 NCT02448797] | |
− | #'''EVIDENCE:''' He J, Su C, Liang W, Xu S, Wu L, Fu X, Zhang X, Ge D, Chen Q, Mao W, Xu L, Chen C, Hu B, Shao G, Hu J, Zhao J, Liu X, Liu Z, Wang Z, Xiao Z, Gong T, Lin W, Li X, Ye F, Liu Y, Ma H, Huang Y, Zhou J, Wang Z, Fu J, Ding L, Mao L, Zhou C. Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir Med. 2021 Sep;9(9):1021-1029. Epub 2021 Jul 21. [https://doi.org/10.1016/s2213-2600(21)00134-x link to original article] ''' | ||
==Osimertinib monotherapy {{#subobject:e73ij6|Regimen=1}}== | ==Osimertinib monotherapy {{#subobject:e73ij6|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:b7891t|Variant=1}}=== | ===Regimen {{#subobject:b7891t|Variant=1}}=== | ||
{| class="wikitable sortable" style="color:white; background-color:#404040" | {| class="wikitable sortable" style="color:white; background-color:#404040" | ||
Line 140: | Line 241: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 146: | Line 247: | ||
|- | |- | ||
|[https://doi.org/10.1056/nejmoa2027071 Wu et al. 2020 (ADAURA)] | |[https://doi.org/10.1056/nejmoa2027071 Wu et al. 2020 (ADAURA)] | ||
− | |2015-2019 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-241-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2015-11 to 2019-02 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
− | |Placebo | + | |[[Non-small_cell_lung_cancer_-_null_regimens#Placebo|Placebo]] |
− | | style="background-color:#1a9850" |Superior DFS<br> | + | | style="background-color:#1a9850" |Superior DFS<sup>1</sup> (primary endpoint)<br>DFS48: 73% vs 38%<br>(HR 0.27, 95% CI 0.21-0.34)<br><br>Superior OS<sup>2</sup> (secondary endpoint)<br>OS60: 85% vs 73%<br>(HR 0.49, 95.03% CI 0.33-0.73) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the January 2023 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy is based on the June 2023 update.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | |||
*EGFR exon 19 deletion or p.L858R mutation, alone or in combination with other EGFR mutations | *EGFR exon 19 deletion or p.L858R mutation, alone or in combination with other EGFR mutations | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Lung_cancer_surgery|Complete resection]] | *[[Surgery#Lung_cancer_surgery|Complete resection]] | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Osimertinib (Tagrisso)]] 80 mg PO once per day | *[[Osimertinib (Tagrisso)]] 80 mg PO once per day | ||
− | |||
'''3-year course''' | '''3-year course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ADAURA:''' Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723. Epub 2020 Sep 19. [https://doi.org/10.1056/nejmoa2027071 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/32955177/ PubMed] [https://clinicaltrials.gov/study/NCT02511106 NCT02511106] | |
− | #'''ADAURA:''' Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723. Epub 2020 Sep 19. [https://doi.org/10.1056/nejmoa2027071 link to original article] ''' | + | ##'''Update:''' Herbst RS, Wu YL, John T, Grohe C, Majem M, Wang J, Kato T, Goldman JW, Laktionov K, Kim SW, Yu CJ, Vu HV, Lu S, Lee KY, Mukhametshina G, Akewanlop C, de Marinis F, Bonanno L, Domine M, Shepherd FA, Urban D, Huang X, Bolanos A, Stachowiak M, Tsuboi M. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023 Apr 1;41(10):1830-1840. Epub 2023 Jan 31. [https://doi.org/10.1200/jco.22.02186 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082285/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36720083/ PubMed] |
+ | ##'''Update:''' Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, Wang J, Goldman JW, Lu S, Su WC, de Marinis F, Shepherd FA, Lee KH, Le NT, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov Y, Wu YL; ADAURA Investigators. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023 Jul 13;389(2):137-147. Epub 2023 Jun 4. [https://doi.org/10.1056/nejmoa2304594 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37272535/ PubMed] | ||
=Advanced or metastatic disease, platinum-exposed= | =Advanced or metastatic disease, platinum-exposed= | ||
==Amivantamab monotherapy {{#subobject:1bgy64|Regimen=1}}== | ==Amivantamab monotherapy {{#subobject:1bgy64|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:agh1t2|Variant=1}}=== | |
− | |||
− | |||
− | ===Regimen | ||
{| class="wikitable sortable" style="color:white; background-color:#404040" | {| class="wikitable sortable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
Line 183: | Line 287: | ||
{| 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 | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791812/ Park et al. 2021 (CHRYSALIS)] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | | style="background-color:# | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-317-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' |
|- | |- | ||
− | |} | + | |} --> |
− | + | |2016-2020 | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |2016- | ||
| style="background-color:#91cf61" |Phase 1 (RT) | | style="background-color:#91cf61" |Phase 1 (RT) | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: Dosing details are from the FDA announcement.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*EGFR exon 20 insertion | *EGFR exon 20 insertion | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | *[[Amivantamab (Rybrevant)]] 1400 mg IV once on day 1 | + | *[[Amivantamab (Rybrevant)]] by the following weight-based criteria: |
+ | **Less than 80 kg: 1050 mg IV once on day 1 | ||
+ | **80 kg or more: 1400 mg IV once on day 1 | ||
'''7-day cycle for 4 cycles, then 14-day cycles''' | '''7-day cycle for 4 cycles, then 14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''CHRYSALIS:''' NCT02609776 | + | #'''CHRYSALIS:''' Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021 Oct 20;39(30):3391-3402. Epub 2021 Aug 2. [https://doi.org/10.1200/jco.21.00662 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791812/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34339292/ PubMed] [https://clinicaltrials.gov/study/NCT02609776 NCT02609776] |
==Mobocertinib monotherapy {{#subobject:8gja7b|Regimen=1}}== | ==Mobocertinib monotherapy {{#subobject:8gja7b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:u157ga|Variant=1}}=== | ===Regimen {{#subobject:u157ga|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 234: | Line 322: | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
! style="width: 33%" |Study | ! style="width: 33%" |Study | ||
− | ! style="width: 33%" | | + | ! style="width: 33%" |Dates of enrollment |
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295177/ Riely et al. 2021 (AP32788-15-101)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295177/ Riely et al. 2021 (AP32788-15-101)] | ||
− | |2016- | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | | style="background-color:#91cf61" |Phase | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-298-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' |
+ | |- | ||
+ | |} --> | ||
+ | |2016-2020 | ||
+ | | style="background-color:#91cf61" |Phase 1/2 (RT) | ||
|} | |} | ||
− | ''Note: this was the dose used in the phase | + | ''Note: this was the dose used in the phase 2 portion.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*EGFR exon 20 insertion mutations | *EGFR exon 20 insertion mutations | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Mobocertinib (Exkivity)]] 160 mg PO once per day on days 1 to 28 | |
− | *[[Mobocertinib (Exkivity)]] 160 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''AP32788-15-101:''' Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Jänne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial. Cancer Discov. 2021 Jul;11(7):1688-1699. Epub 2021 Feb 25. [https://doi.org/10.1158/2159-8290.cd-20-1598 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295177/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33632775/ PubMed] [https://clinicaltrials.gov/study/NCT02716116 NCT02716116] | |
− | #'''AP32788-15-101:''' Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Jänne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial. Cancer Discov. 2021 Jul;11(7):1688-1699. Epub 2021 Feb 25. [https://doi.org/10.1158/2159-8290.cd-20-1598 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295177/ link to PMC article] ''' | + | ##'''Update:''' Zhou C, Ramalingam SS, Kim TM, Kim SW, Yang JC, Riely GJ, Mekhail T, Nguyen D, Garcia Campelo MR, Felip E, Vincent S, Jin S, Griffin C, Bunn V, Lin J, Lin HM, Mehta M, Jänne PA. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial. JAMA Oncol. 2021 Dec 1;7(12):e214761. Epub 2021 Dec 16. Erratum in: JAMA Oncol. 2022 Feb 24. [https://doi.org/10.1001/jamaoncol.2021.4761 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8517885/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34647988/ PubMed] |
=Advanced or metastatic disease, EGFR inhibitor-naive= | =Advanced or metastatic disease, EGFR inhibitor-naive= | ||
− | |||
==Afatinib monotherapy {{#subobject:1bf6db|Regimen=1}}== | ==Afatinib monotherapy {{#subobject:1bf6db|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 30 mg/day {{#subobject:f69d3b|Variant=1}}=== | ===Regimen variant #1, 30 mg/day {{#subobject:f69d3b|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 266: | Line 355: | ||
|- | |- | ||
|} | |} | ||
− | ''This is the FDA-recommended dose for patients with "severe renal impairment".'' | + | ''Note: This is the FDA-recommended dose for patients with "severe renal impairment".'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Afatinib (Gilotrif)]] 30 mg PO once per day | *[[Afatinib (Gilotrif)]] 30 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 40 mg/day {{#subobject:130d4a|Variant=1}}=== | ===Regimen variant #2, 40 mg/day {{#subobject:130d4a|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 280: | Line 369: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70086-4 Yang et al. 2012 (LUX-Lung 2)] |
|2007-2009 | |2007-2009 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 (RT) |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#9ebcda" |ORR: 61% | | style="background-color:#9ebcda" |ORR: 61% | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | |[https://doi.org/10.1200/jco.2012.44.2806 Sequist et al. 2013 (LUX-Lung 3)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-60-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2009-2011 | |2009-2011 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | ||
− | |[[#Cisplatin_. | + | |[[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.1 vs 6.9 mo<br>(HR 0.58, 95% CI 0.43-0.78) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70604-1 Wu et al. 2014 (LUX-Lung 6)] |
− | |2010-2011 | + | |2010-04-27 to 2011-11-16 |
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | ||
|[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11 vs 5.6 mo<br>(HR 0.28, 95% CI 0.20-0.39) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30033-X Park et al. 2016 (LUX-Lung 7)] |
|2011-2013 | |2011-2013 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>Median PFS: 11 vs 10.9 mo<br>(HR 0.73, 95% CI 0.57-0.95) |
|- | |- | ||
|} | |} | ||
− | ====Biomarker | + | <div class="toccolours" style="background-color:#fdcdac"> |
+ | ====Biomarker eligibility criteria==== | ||
+ | *LUX-Lung 2: activating EGFR mutations within exons 18–21 | ||
+ | *LUX-Lung 3 & LUX-Lung 6: Activating EGFR mutation with exon 19 deletions, L858R, insertions in exon 20, L861Q, G719S, G719A, G719C, T790M, or S768I | ||
+ | *LUX-Lung 7: Activating EGFR mutation with exon 19 deletion and/or L858R | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Afatinib (Gilotrif)]] 40 mg PO once per day, taken 1 hour before eating food (LUX-Lung 2: "no food intake immediately before or after afatinib") | ||
+ | '''Continued indefinitely''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#fff2ae"> | ||
+ | ====Dose and schedule modifications==== | ||
+ | *In LUX-Lung 3 & LUX-Lung 7, patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event. | ||
+ | </div></div> | ||
− | + | ===References=== | |
− | + | #'''LUX-Lung 2:''' Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. [https://doi.org/10.1016/S1470-2045(12)70086-4 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22452895/ PubMed] [https://clinicaltrials.gov/study/NCT00525148 NCT00525148] | |
− | + | ##'''Pooled subgroup analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://doi.org/10.1016/S1470-2045(15)00026-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236/ PubMed] | |
− | * | + | #'''LUX-Lung 3:''' Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.44.2806 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23816960/ PubMed] [https://clinicaltrials.gov/study/NCT00949650 NCT00949650] |
+ | ##'''HRQoL analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.46.1764 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23816967/ PubMed] | ||
+ | ##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. [https://doi.org/10.1016/S1470-2045(14)71173-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191/ PubMed] | ||
+ | ##'''Pooled subgroup analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://doi.org/10.1016/S1470-2045(15)00026-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236/ PubMed] | ||
+ | ##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. [https://doi.org/10.1016/j.jtho.2015.11.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294/ PubMed] | ||
+ | #'''LUX-Lung 6:''' Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. Epub 2014 Jan 15. [https://doi.org/10.1016/S1470-2045(13)70604-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24439929/ PubMed] [https://clinicaltrials.gov/study/NCT01121393 NCT01121393] | ||
+ | ##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. [https://doi.org/10.1016/S1470-2045(14)71173-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191/ PubMed] | ||
+ | ##'''Pooled subgroup analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://doi.org/10.1016/S1470-2045(15)00026-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236/ PubMed] | ||
+ | ##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. [https://doi.org/10.1016/j.jtho.2015.11.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294/ PubMed] | ||
+ | #'''LUX-Lung 7:''' Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [https://doi.org/10.1016/S1470-2045(16)30033-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27083334/ PubMed] [https://clinicaltrials.gov/study/NCT01466660 NCT01466660] | ||
+ | ==Apatinib & Gefitinib {{#subobject:1bf5yg|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:1acg4a|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%" |Dates 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.2021.05.006 Zhao et al. 2021 (CTONG1706)] | ||
+ | |2017-08 to 2018-12 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 13.7 vs 10.2 mo<br>(HR 0.71, 95% CI 0.54-0.95) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or exon 21 L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Apatinib (Aitan)]] 500 mg PO once per day | ||
+ | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''CTONG1706:''' Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q, Wu G, Jiang O, Du X, Liu J, Gu W, Hou Z, Wang Q, Zheng R, Zhou X, Zhang L. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. Epub 2021 May 24. [https://doi.org/10.1016/j.jtho.2021.05.006 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34033974/ PubMed] [https://clinicaltrials.gov/study/NCT02824458 NCT02824458] | ||
+ | ==Aumolertinib monotherapy {{#subobject:1bgccg|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:67cx4a|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/PMC9509093/ Lu et al. 2022 (AENEAS)] | ||
+ | |2018-11-30 to 2019-09-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 19.3 vs 9.9 mo<br>(HR 0.46, 95% CI 0.36-0.60) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or L858R | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Aumolertinib (Amelie)]] 110 mg PO once per day | |
− | *[[ | ||
− | |||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''AENEAS:''' Lu S, Dong X, Jian H, Chen J, Chen G, Sun Y, Ji Y, Wang Z, Shi J, Lu J, Chen S, Lv D, Zhang G, Liu C, Li J, Yu X, Lin Z, Yu Z, Wang Z, Cui J, Xu X, Fang J, Feng J, Xu Z, Ma R, Hu J, Yang N, Zhou X, Wu X, Hu C, Zhang Z, Lu Y, Hu Y, Jiang L, Wang Q, Guo R, Zhou J, Li B, Hu C, Tong W, Zhang H, Ma L, Chen Y, Jie Z, Yao Y, Zhang L, Jie W, Li W, Xiong J, Ye X, Duan J, Yang H, Sun M, Sun C, Wei H, Li C, Ali SM, Miller VA, Wu Q. AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations. J Clin Oncol. 2022 Sep 20;40(27):3162-3171. Epub 2022 May 17. [https://doi.org/10.1200/jco.21.02641 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509093/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35580297/ PubMed] [https://clinicaltrials.gov/study/NCT03849768 NCT03849768] | |
− | #''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==Carboplatin & Docetaxel {{#subobject:bdce59|Regimen=1}}== | ==Carboplatin & Docetaxel {{#subobject:bdce59|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
DCb: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''ar'''<u>b</u>'''oplatin | 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}}=== | ===Regimen {{#subobject:bce236|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70393-X Rossell et al. 2012 (EURTAC)] |
|2007-2011 | |2007-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 360: | Line 513: | ||
|- | |- | ||
|} | |} | ||
− | ====Biomarker | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | + | ====Biomarker eligibility criteria==== | |
*Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21 | *Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21 | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1 | ||
*[[Docetaxel (Taxotere)]] 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 4 cycles''' | |
− | '''21-day cycles''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https://doi.org/10.1016/S1470-2045(11)70393-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22285168/ PubMed] [https://clinicaltrials.gov/study/NCT00446225 NCT00446225] | |
− | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https:// | ||
− | |||
==Carboplatin & Gemcitabine (GCb) {{#subobject:8669e|Regimen=1}}== | ==Carboplatin & Gemcitabine (GCb) {{#subobject:8669e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''arboplatin | GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''arboplatin | ||
<br>GCa: '''<u>G</u>'''emcitabine & '''<u>Ca</u>'''rboplatin | <br>GCa: '''<u>G</u>'''emcitabine & '''<u>Ca</u>'''rboplatin | ||
<br>GCb: '''<u>G</u>'''emcitabine & '''<u>C</u>'''ar'''<u>b</u>'''oplatin | <br>GCb: '''<u>G</u>'''emcitabine & '''<u>C</u>'''ar'''<u>b</u>'''oplatin | ||
− | ===Regimen {{#subobject:cfb199|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 5/1000 {{#subobject:cfb199|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70393-X Rossell et al. 2012 (EURTAC)] |
|2007-2011 | |2007-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 397: | Line 544: | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70184-X Zhou et al. 2011 (CTONG-0802)] |
− | |2008-2009 | + | |2008-08-24 to 2009-07-17 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
Line 404: | Line 551: | ||
|- | |- | ||
|} | |} | ||
− | ====Biomarker | + | <div class="toccolours" style="background-color:#fdcdac"> |
− | + | ====Biomarker eligibility criteria==== | |
*Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21 | *Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21 | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | *[[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 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycle for up to 4 cycles''' | '''21-day cycle for up to 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 5/1250 {{#subobject:7e79d9|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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)] | ||
+ | |2009-04-29 to 2010-09-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Non-small_cell_lung_cancer,_EGFR-mutated#Carboplatin_.26_Gemcitabine_.28GCb.29.2FErlotinib|Carboplatin & Gemcitabine/Erlotinib]]<br>1b. [[Non-small_cell_lung_cancer,_EGFR-mutated#Cisplatin_.26_Gemcitabine.2FErlotinib|GC/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 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''CTONG-0802:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [https://doi.org/10.1016/S1470-2045(11)70184-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21783417/ PubMed] [https://clinicaltrials.gov/study/NCT00874419 NCT00874419] | |
− | #'''CTONG-0802:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [https:// | + | ##'''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [https://doi.org/10.1093/annonc/mdv276 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26141208/ PubMed] |
− | ##'''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [https://doi.org/10.1093/annonc/mdv276 link to original article] ''' | + | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https://doi.org/10.1016/S1470-2045(11)70393-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22285168/ PubMed] [https://clinicaltrials.gov/study/NCT00446225 NCT00446225] |
− | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https:// | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23782814/ PubMed] [https://clinicaltrials.gov/study/NCT00883779 NCT00883779] |
==Carboplatin & Gemcitabine/Erlotinib {{#subobject:3465c3|Regimen=1}}== | ==Carboplatin & Gemcitabine/Erlotinib {{#subobject:3465c3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:821638|Variant=1}}=== | ===Regimen {{#subobject:821638|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70254-7 Wu et al. 2013 (FASTACT-2)] |
− | |2009-2010 | + | |2009-04-29 to 2010-09-09 |
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | + | |1a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br>1b. [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] |
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.6 vs 6 mo<br>(HR 0.57, 95% CI 0.47-0.69)<br><br>Seems to have superior OS (secondary endpoint)<br>Median OS: 18.3 vs 15.2 mo<br>(HR 0.79, 95% CI 0.64-0.99) |
|- | |- | ||
|} | |} | ||
''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.'' | ''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==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | *[[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 | *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 15 to 28 | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 15 to 28 | ||
− | + | '''28-day cycle for 6 cycles''' | |
− | '''28-day cycle for | + | </div></div> |
===References=== | ===References=== | ||
− | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23782814/ PubMed] [https://clinicaltrials.gov/study/NCT00883779 NCT00883779] | |
− | #'''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:// | ||
− | |||
==Carboplatin & Paclitaxel (CP) {{#subobject:c5fbdf|Regimen=1}}== | ==Carboplatin & Paclitaxel (CP) {{#subobject:c5fbdf|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel | CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''aclitaxel | ||
<br>PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin | <br>PC: '''<u>P</u>'''aclitaxel & '''<u>C</u>'''arboplatin | ||
<br>TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin | <br>TC: '''<u>T</u>'''axol (Paclitaxel) & '''<u>C</u>'''arboplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5f5ff1|Variant=1}}=== | ===Regimen {{#subobject:5f5ff1|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] |
|2006-2009 | |2006-2009 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 479: | Line 638: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 60 minutes once on day 1, '''given second''' | *[[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''' | *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first''' | ||
− | |||
'''21-day cycle for at least 3 cycles''' | '''21-day cycle for at least 3 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''NEJ002:''' Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. [https://doi.org/10.1056/NEJMoa0909530 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20573926/ PubMed] UMIN000000376 | ||
+ | ##'''HRQoL analysis:''' Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. [https://doi.org/10.1634/theoncologist.2011-0426 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380886/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22581822/ PubMed] | ||
+ | ##'''Update:''' Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. [https://doi.org/10.1093/annonc/mds214 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22967997/ PubMed] | ||
+ | ==Carboplatin & Pemetrexed {{#subobject:7ufd1d|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 4 cycles of carboplatin {{#subobject:15c44d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/nejmoa2306441 Zhou et al. 2023 (PAPILLON)] | ||
+ | |2020-12 to 2022-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Carboplatin.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: To our knowledge, this regimen variant 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:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 20 insertions | ||
+ | </div> | ||
+ | <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 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 6 cycles of carboplatin {{#subobject:15c37d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/PMC5519810/ Patil et al. 2017] | ||
+ | |2012-2016 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: To our knowledge, this regimen variant 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:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *Activating EGFR mutation in exons 18, 19, or 21 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6: AUC 5 IV over 30 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''' | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. [https://doi.org/10.1136/esmoopen-2017-000168 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519810/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28761735/ PubMed] | ||
+ | #'''PAPILLON:''' Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourão Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med. 2023 Nov 30;389(22):2039-2051. Epub 2023 Oct 21. [https://doi.org/10.1056/nejmoa2306441 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37870976/ PubMed] [https://clinicaltrials.gov/study/NCT04538664 NCT04538664] | ||
+ | ==Carboplatin, Pemetrexed, Amivantamab {{#subobject:7ufanv|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, lower-dose amivantamab {{#subobject:5th24d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/nejmoa2306441 Zhou et al. 2023 (PAPILLON)] | ||
+ | |2020-12 to 2022-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.4 vs 6.7 mo<br>(HR 0.40, 95% CI 0.30-0.53) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing less than 80 kg.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 20 insertions | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1400 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 1750 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, higher-dose amivantamab {{#subobject:15c37d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/nejmoa2306441 Zhou et al. 2023 (PAPILLON)] | ||
+ | |2020-12 to 2022-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.4 vs 6.7 mo<br>(HR 0.40, 95% CI 0.30-0.53) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing 80 kg or more.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 20 insertions | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1750 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 2100 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
+ | #'''PAPILLON:''' Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourão Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med. 2023 Nov 30;389(22):2039-2051. Epub 2023 Oct 21. [https://doi.org/10.1056/nejmoa2306441 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37870976/ PubMed] [https://clinicaltrials.gov/study/NCT04538664 NCT04538664] | ||
− | # | + | ==Carboplatin, Osimertinib, Pemetrexed {{#subobject:cbxib4|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ##''' | + | ===Regimen {{#subobject:8fcpcb|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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/nejmoa2306434 Planchard et al. 2023 (FLAURA2)] | ||
+ | |2020-06-01 to 2021-12-22 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS24: 57% vs 41%<br>(HR 0.62, 95% CI 0.49-0.79) | ||
+ | |- | ||
+ | |} | ||
+ | <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==== | ||
+ | *[[Osimertinib (Tagrisso)]] 80 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''FLAURA2:''' Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. [https://doi.org/10.1056/nejmoa2306434 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37937763/ PubMed] [https://clinicaltrials.gov/study/NCT04035486 NCT04035486] | ||
+ | ##'''Subgroup analysis:''' Jänne PA, Planchard D, Kobayashi K, Cheng Y, Lee CK, Valdiviezo N, Laktionov K, Yang TY, Yu Y, Kato T, Jiang L, Chewaskulyong B, Lucien Geater S, Maurel JM, Rojas C, Takahashi T, Havel L, Shepherd FA, Tanaka K, Ghiorghiu D, Amin NP, Armenteros-Monterroso E, Huang X, Chaudhry AA, Yang JC. CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2024 Mar 1;42(7):808-820. Epub 2023 Dec 2. [https://doi.org/10.1200/jco.23.02219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10906563/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38042525/ PubMed] | ||
==Cisplatin & Docetaxel (DC) {{#subobject:179d86|Regimen=1}}== | ==Cisplatin & Docetaxel (DC) {{#subobject:179d86|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''isplatin | DC: '''<u>D</u>'''ocetaxel & '''<u>C</u>'''isplatin | ||
<br>DP: '''<u>D</u>'''ocetaxel & '''<u>P</u>'''latinol (Cisplatin) | <br>DP: '''<u>D</u>'''ocetaxel & '''<u>P</u>'''latinol (Cisplatin) | ||
<br>Doc-Cis: '''<u>Doc</u>'''etaxel & '''<u>Cis</u>'''platin | <br>Doc-Cis: '''<u>Doc</u>'''etaxel & '''<u>Cis</u>'''platin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 75/75 {{#subobject:154c29|Variant=1}}=== | ===Regimen variant #1, 75/75 {{#subobject:154c29|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70393-X Rossell et al. 2012 (EURTAC)] |
|2007-2011 | |2007-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 514: | Line 828: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for up to 4 cycles''' | '''21-day cycle for up to 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 80/60 {{#subobject:5a7d3b|Variant=1}}=== | ===Regimen variant #2, 80/60 {{#subobject:5a7d3b|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(09)70364-X Mitsudomi et al. 2009 (WJTOG3405)] |
|2006-2009 | |2006-2009 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 537: | Line 854: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given second''' | *[[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''' | *[[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''' | '''21-day cycle for 3 to 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''WJTOG3405:''' Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. [https://doi.org/10.1016/S1470-2045(09)70364-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20022809/ PubMed] UMIN000000539 | |
− | #'''WJTOG3405:''' Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. [https:// | + | ##'''Update:''' Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. [https://doi.org/10.1093/annonc/mdz399 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31553438/ PubMed] |
− | ##'''Update:''' Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. [https://doi.org/10.1093/annonc/mdz399 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31553438 PubMed] | + | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https://doi.org/10.1016/S1470-2045(11)70393-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22285168/ PubMed] [https://clinicaltrials.gov/study/NCT00446225 NCT00446225] |
− | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https:// | ||
==Cisplatin & Gemcitabine (GC) {{#subobject:fb3ee0|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) {{#subobject:fb3ee0|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin | GC: '''<u>G</u>'''emcitabine & '''<u>C</u>'''isplatin | ||
<br>GP: '''<u>G</u>'''emcitabine & '''<u>P</u>'''latinol (Cisplatin) | <br>GP: '''<u>G</u>'''emcitabine & '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 75/1000 {{#subobject:6a4b24|Variant=1}}=== | ===Regimen variant #1, 75/1000 {{#subobject:6a4b24|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70604-1 Wu et al. 2014 (LUX-Lung 6)] |
− | |2010-2011 | + | |2010-04-27 to 2011-11-16 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Afatinib_monotherapy|Afatinib]] | |[[#Afatinib_monotherapy|Afatinib]] | ||
Line 572: | Line 888: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR mutation-positive | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant #2, 75/1250 {{#subobject:0e126e|Variant=1}}=== | + | <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;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70393-X Rossell et al. 2012 (EURTAC)] |
|2007-2011 | |2007-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 595: | Line 914: | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | |[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | ||
− | |2011-2012 | + | |2011-03 to 2012-06 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
Line 601: | Line 920: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *EURTAC: EGFR exon 19 deletion or p.L858R mutation in exon 21 | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1 | *[[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 | *[[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 4 cycles''' | '''21-day cycle for up to 4 cycles''' | ||
− | + | </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%"|Dates 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)] | ||
+ | |2009-04-29 to 2010-09-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[Non-small_cell_lung_cancer,_EGFR-mutated#Carboplatin_.26_Gemcitabine_.28GCb.29.2FErlotinib|Carboplatin & Gemcitabine/Erlotinib]]<br>1b. [[Non-small_cell_lung_cancer,_EGFR-mutated#Cisplatin_.26_Gemcitabine.2FErlotinib|GC/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==== | ||
+ | *[[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 6 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https://doi.org/10.1016/S1470-2045(11)70393-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22285168/ PubMed] [https://clinicaltrials.gov/study/NCT00446225 NCT00446225] | |
− | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https:// | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23782814/ PubMed] [https://clinicaltrials.gov/study/NCT00883779 NCT00883779] |
− | #'''LUX-Lung 6:''' Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. [https:// | + | #'''LUX-Lung 6:''' Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. Epub 2014 Jan 15. [https://doi.org/10.1016/S1470-2045(13)70604-1 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24439929/ PubMed] [https://clinicaltrials.gov/study/NCT01121393 NCT01121393] |
− | ##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. [https:// | + | ##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. [https://doi.org/10.1016/S1470-2045(14)71173-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191/ PubMed] |
− | ##'''Pooled analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https:// | + | ##'''Pooled subgroup analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://doi.org/10.1016/S1470-2045(15)00026-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236/ PubMed] |
− | ##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. [ | + | ##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. [https://doi.org/10.1016/j.jtho.2015.11.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294/ PubMed] |
− | #'''ENSURE:''' Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. [https://doi.org/10.1093/annonc/mdv270 link to original article] ''' | + | #'''ENSURE:''' Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. [https://doi.org/10.1093/annonc/mdv270 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26105600/ PubMed] [https://clinicaltrials.gov/study/NCT01342965 NCT01342965] |
==Cisplatin & Gemcitabine/Erlotinib {{#subobject:26da43|Regimen=1}}== | ==Cisplatin & Gemcitabine/Erlotinib {{#subobject:26da43|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:d88ccb|Variant=1}}=== | ===Regimen {{#subobject:d88ccb|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70254-7 Wu et al. 2013 (FASTACT-2)] |
− | |2009-2010 | + | |2009-04-29 to 2010-09-09 |
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] | + | |1a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br>1b. [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_.28GC.29_2|Cisplatin & Gemcitabine]] |
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 7.6 vs 6 mo<br>(HR 0.57, 95% CI 0.47-0.69)<br><br>Seems to have superior OS (secondary endpoint)<br>Median OS: 18.3 vs 15.2 mo<br>(HR 0.79, 95% CI 0.64-0.99) |
|- | |- | ||
|} | |} | ||
''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.'' | ''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==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Gemcitabine (Gemzar)]] 1250 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 15 to 28 | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 15 to 28 | ||
− | + | '''28-day cycle for 6 cycles''' | |
− | '''28-day cycle for | + | </div></div> |
===References=== | ===References=== | ||
− | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23782814/ PubMed] [https://clinicaltrials.gov/study/NCT00883779 NCT00883779] | |
− | #'''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:// | ||
− | |||
==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}== | ==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin | Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin | ||
<br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed | <br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed | ||
− | ===Regimen {{#subobject:8fdaa3|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, limited duration {{#subobject:8fdaa3|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
|<small>'''FDA-recommended dose'''</small> | |<small>'''FDA-recommended dose'''</small> | ||
Line 667: | Line 1,001: | ||
{| 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 | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 677: | Line 1,011: | ||
|[[#Afatinib_monotherapy|Afatinib]] | |[[#Afatinib_monotherapy|Afatinib]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *Activating mutations in EGFR | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV 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==== | ||
+ | *(as described in JMDB): | ||
+ | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to pemetrexed | ||
+ | *[[Folic acid (Folate)]] 1 mg PO once per day | ||
+ | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for pemetrexed." | ||
+ | '''21-day cycle for 4 to 6 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, with maintenance {{#subobject:8fdab8|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%"|Dates 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/mdx359 Shi et al. 2017 (CONVINCE)] | |[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | ||
− | |2013-2014 | + | |2013-01 to 2014-08 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[ | + | |[[#Icotinib_monotherapy_2|Icotinib]] |
− | | style="background-color:#d73027" | | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19/21 mutations | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Cisplatin (Platinol)]] as follows: | |
− | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | + | **Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1 |
− | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV | + | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*(as described in JMDB): | *(as described in JMDB): | ||
− | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to | + | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to pemetrexed |
*[[Folic acid (Folate)]] 1 mg PO once per day | *[[Folic acid (Folate)]] 1 mg PO once per day | ||
− | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for | + | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for pemetrexed." |
− | + | '''21-day cycles''' | |
− | '''21-day | + | </div></div> |
− | === | + | ===References=== |
− | + | #'''LUX-Lung 3:''' Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.44.2806 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23816960/ PubMed] [https://clinicaltrials.gov/study/NCT00949650 NCT00949650] | |
− | + | ##'''HRQoL analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [https://doi.org/10.1200/jco.2012.46.1764 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23816967/ PubMed] | |
+ | ##'''Pooled update:''' Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. [https://doi.org/10.1016/S1470-2045(14)71173-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25589191/ PubMed] | ||
+ | ##'''Pooled subgroup analysis:''' Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. [https://doi.org/10.1016/S1470-2045(15)00026-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26051236/ PubMed] | ||
+ | ##'''Subgroup analysis:''' Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. [https://doi.org/10.1016/j.jtho.2015.11.014 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26823294/ PubMed] | ||
+ | #'''CONVINCE:''' Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. [https://doi.org/10.1093/annonc/mdx359 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28945850/ PubMed] [https://clinicaltrials.gov/study/NCT01719536 NCT01719536] | ||
+ | ==Cisplatin, Osimertinib, Pemetrexed {{#subobject:aoxib4|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:8fcpo3|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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/nejmoa2306434 Planchard et al. 2023 (FLAURA2)] | ||
+ | |2020-06-01 to 2021-12-22 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |[[#Osimertinib_monotherapy_2|Osimertinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS24: 57% vs 41%<br>(HR 0.62, 95% CI 0.49-0.79) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 4: 75 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Osimertinib (Tagrisso)]] 80 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''FLAURA2:''' Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. [https://doi.org/10.1056/nejmoa2306434 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37937763/ PubMed] [https://clinicaltrials.gov/study/NCT04035486 NCT04035486] | |
− | #''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
==Dacomitinib monotherapy {{#subobject:c0a00a|Regimen=1}}== | ==Dacomitinib monotherapy {{#subobject:c0a00a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:4fcaa3|Variant=1}}=== | ===Regimen {{#subobject:4fcaa3|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 724: | Line 1,110: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 730: | Line 1,116: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)] | ||
− | |2008- | + | |2008-2009 |
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
− | | style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 2.9 vs 1.9 mo<br>(HR 0.66, 95% CI 0.47-0.91) | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 2.9 vs 1.9 mo<br>(HR 0.66, 95% CI 0.47-0.91) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70452-8 Ramalingam et al. 2014 (ARCHER 1009)] |
|2011-2013 | |2011-2013 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
Line 741: | Line 1,127: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 2.6 vs 2.6 mo<br>(HR 0.94, 95% CI 0.80-1.10) | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 2.6 vs 2.6 mo<br>(HR 0.94, 95% CI 0.80-1.10) | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(17)30608-3 Wu et al. 2017 (ARCHER 1050)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-141-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2013-2015 | |2013-2015 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 34.1 vs 27 mo<br>(HR 0.75, 95% CI 0.59-0.95) | + | | style="background-color:#91cf60" |Superior PFS (primary endpoint)<br>Median PFS: 14.7 vs 9.2 mo<br>(HR 0.59, 95% CI 0.47-0.74)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 34.1 vs 27 mo<br>(HR 0.75, 95% CI 0.59-0.95) |
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup>Reported efficacy for ARCHER 1050 is based on the 2021 update.'' | + | ''<sup>1</sup>Reported efficacy for OS in ARCHER 1050 is based on the 2021 update.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*A7471028 & ARCHER 1009: None | *A7471028 & ARCHER 1009: None | ||
*ARCHER 1050: Activating mutations in EGFR | *ARCHER 1050: Activating mutations in EGFR | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Dacomitinib (Vizimpro)]] 45 mg PO once per day on days 1 to 28 | |
− | *[[Dacomitinib (Vizimpro)]] 45 mg PO once per day | + | '''28-day cycles''' |
− | + | </div></div> | |
− | ''' | ||
− | |||
===References=== | ===References=== | ||
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. --> | <!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. --> | ||
− | + | #'''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22753918/ PubMed] [https://clinicaltrials.gov/study/NCT00769067 NCT00769067] | |
− | #'''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22753918 PubMed] NCT00769067 | + | #'''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.[https://doi.org/10.1016/S1470-2045(14)70452-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25439691/ PubMed] [https://clinicaltrials.gov/study/NCT01360554 NCT01360554] |
− | #'''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.[https:// | + | #'''ARCHER 1050:''' Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. [https://doi.org/10.1016/S1470-2045(17)30608-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28958502/ PubMed] [https://clinicaltrials.gov/study/NCT01774721 NCT01774721] |
− | #'''ARCHER 1050:''' Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. [https:// | + | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. [https://doi.org/10.1200/JCO.2018.78.7994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29864379/ PubMed] |
− | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. [https://doi.org/10.1200/JCO.2018.78.7994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29864379 PubMed] | + | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. [https://doi.org/10.1007/s40265-020-01441-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7932969/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33331989/ PubMed] |
− | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. [https://doi.org/10.1007/s40265-020-01441-6 link to original article] [ | ||
==Erlotinib monotherapy {{#subobject:c3c726|Regimen=1}}== | ==Erlotinib monotherapy {{#subobject:c3c726|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 150 mg/d {{#subobject:d27efc|Variant=1}}=== | ===Regimen variant #1, 150 mg/d {{#subobject:d27efc|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 779: | Line 1,166: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70393-X Rossell et al. 2012 (EURTAC)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-58-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2007-2011 | |2007-2011 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | ||
− | | | + | |1a. [[#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]<br>1b. [[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]]<br>1c. [[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]]<br>1d. [[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] |
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 9.7 vs 5.2 mo<br>(HR 0.37, 95% CI 0.25-0.54) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9.7 vs 5.2 mo<br>(HR 0.37, 95% CI 0.25-0.54) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(11)70184-X Zhou et al. 2011 (CTONG-0802)] |
− | |2008-2009 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-57-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2008-08-24 to 2009-07-17 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | |[[#Carboplatin_.26_Gemcitabine_.28GCb.29|Carboplatin & Gemcitabine]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 13.1 vs 4.6 mo<br>(HR 0.16, 95% CI 0.10-0.26) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 13.1 vs 4.6 mo<br>(HR 0.16, 95% CI 0.10-0.26) |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ Ramalingam et al. 2012 (A7471028)] | ||
− | |2008- | + | |2008-2009 |
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#Dacomitinib_monotherapy|Dacomitinib]] | |[[#Dacomitinib_monotherapy|Dacomitinib]] | ||
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
Line 804: | Line 1,199: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ Yang et al. 2017 (CTONG 0901)] | ||
|2009-2014 | |2009-2014 | ||
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:# | + | | style="background-color:#d9ef8b" |Might have superior PFS (primary endpoint)<br>Median PFS: 13 vs 10.4 mo<br>(HR 0.81, 95% CI 0.62-1.05) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70381-X Seto et al. 2014 (JO25567)] |
|2011-2012 | |2011-2012 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | |[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | ||
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | |[https://doi.org/10.1093/annonc/mdv270 Wu et al. 2015 (ENSURE)] | ||
− | |2011-2012 | + | |2011-03 to 2012-06 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | |[[#Cisplatin_.26_Gemcitabine_.28GC.29|Cisplatin & Gemcitabine]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11.0 vs 5.5 mo<br>(HR 0.34, 95% CI 0.22-0.51) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.0 vs 5.5 mo<br>(HR 0.34, 95% CI 0.22-0.51)<br><br>Did not meet secondary endpoint of OS<br>Median OS: 26.3 vs 25.5 mo<br>(HR 0.91, 95% CI 0.63-1.31) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70452-8 Ramalingam et al. 2014 (ARCHER 1009)] |
|2011-2013 | |2011-2013 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 826: | Line 1,221: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] |
|2014-2016 | |2014-2016 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 832: | Line 1,227: | ||
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(19)30035-X Saito et al. 2019 (NEJ026)] |
− | |2015-2016 | + | |2015-06-03 to 2016-08-31 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | |[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] | ||
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(19)30634-5 Nakagawa et al. 2019 (RELAY)] | ||
+ | |2016-01-28 to 2018-02-01 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Erlotinib_.26_Ramucirumab|Erlotinib & Ramucirumab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ Kelly et al. 2019 (SOLAR<sub>NSCLC</sub>)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ Kelly et al. 2019 (SOLAR<sub>NSCLC</sub>)] | ||
− | |2016-2017 | + | |2016-02-11 to 2017-12-21 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Naquotinib_monotherapy_999|Naquotinib]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<br>Median PFS: 9.6 vs 9.3 mo<br>(HR 0.62) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ccell.2021.07.005 Zhou et al. 2021 (ARTEMIS-CTONG1509)] | ||
+ | |2016-05 to 2017-07 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] |
− | | style="background-color:# | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.jtho.2022.05.008 Piccirillo et al. 2022 (BEVERLY)] |
− | |2016- | + | |2016-2019 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[#Erlotinib_. | + | |[[#Erlotinib_.26_Bevacizumab|Erlotinib & Bevacizumab]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
Line 853: | Line 1,260: | ||
''<sup>1</sup>Reported efficacy for FLAURA is based on the 2019 update.''<br> | ''<sup>1</sup>Reported efficacy for FLAURA is based on the 2019 update.''<br> | ||
''Note: these are all trials restricted to patients with EGFR-mutated lung cancer. Some trials of erlotinib in unselected populations nevertheless had high rates of EGFR-mutated lung cancers, due to the nature of the populations studied. See the [[Non-small cell lung cancer|main NSCLC page]] for these trials. SOLAR should not be confused with the trial by the same name in gastric cancer.'' | ''Note: these are all trials restricted to patients with EGFR-mutated lung cancer. Some trials of erlotinib in unselected populations nevertheless had high rates of EGFR-mutated lung cancers, due to the nature of the populations studied. See the [[Non-small cell lung cancer|main NSCLC page]] for these trials. SOLAR should not be confused with the trial by the same name in gastric cancer.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28 | |
− | *[[Erlotinib (Tarceva)]] 150 mg PO once per day | + | '''28-day cycles''' |
− | + | </div></div><br> | |
− | ''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
===Regimen variant #2, low-dose {{#subobject:e26eec|Variant=1}}=== | ===Regimen variant #2, low-dose {{#subobject:e26eec|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ Yeo et al. 2010] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ Yeo et al. 2010] | ||
+ | |2004-2010 | ||
| style="background-color:#ffffbe" |Retrospective | | style="background-color:#ffffbe" |Retrospective | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Erlotinib (Tarceva)]] 25 mg PO once per day on days 1 to 21 | |
− | *[[Erlotinib (Tarceva)]] 25 mg PO once per day | + | '''21-day cycles''' |
− | + | </div></div> | |
− | ''' | ||
===References=== | ===References=== | ||
− | + | #'''Retrospective:''' Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20512075/ PubMed] | |
− | #'''Retrospective:''' Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20512075 PubMed] | + | #'''CTONG-0802:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [https://doi.org/10.1016/S1470-2045(11)70184-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21783417/ PubMed] [https://clinicaltrials.gov/study/NCT00874419 NCT00874419] |
− | #'''CTONG-0802:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [https:// | + | ##'''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [https://doi.org/10.1093/annonc/mdv276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26141208/ PubMed] |
− | ##'''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [https://doi.org/10.1093/annonc/mdv276 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26141208 PubMed] | + | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https://doi.org/10.1016/S1470-2045(11)70393-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22285168/ PubMed] [https://clinicaltrials.gov/study/NCT00446225 NCT00446225] |
− | #'''EURTAC:''' Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. [https:// | ||
<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. --> | <!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, June 4-8, 2010, Chicago, IL; the 35th Congress of the European Society for Medical Oncology, October 8-12, 2010, Milan, Italy; and the 14th World Conference on Lung Cancer, July 3-7, 2011, Amsterdam, the Netherlands. --> | ||
− | #'''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] ''' | + | #'''A7471028:''' Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. [https://doi.org/10.1200/JCO.2011.40.9433 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5321098/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22753918/ PubMed] [https://clinicaltrials.gov/study/NCT00769067 NCT00769067] |
− | #'''JO25567:''' Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. [https:// | + | #'''JO25567:''' Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. [https://doi.org/10.1016/S1470-2045(14)70381-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25175099/ PubMed] JapicCTI-111390 |
− | #'''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15. [https:// | + | #'''ARCHER 1009:''' Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70452-8 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25439691/ PubMed] [https://clinicaltrials.gov/study/NCT01360554 NCT01360554] |
− | #'''ENSURE:''' Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. [https://doi.org/10.1093/annonc/mdv270 link to original article] ''' | + | #'''ENSURE:''' Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. [https://doi.org/10.1093/annonc/mdv270 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26105600/ PubMed] [https://clinicaltrials.gov/study/NCT01342965 NCT01342965] |
− | + | #'''CTONG 0901:''' Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. [https://doi.org/10.1038/bjc.2016.456 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28103612/ PubMed] [https://clinicaltrials.gov/study/NCT01024413 NCT01024413] | |
− | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https:// | + | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https://doi.org/10.1056/NEJMoa1713137 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29151359/ PubMed] [https://clinicaltrials.gov/study/NCT02296125 NCT02296125] |
− | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097 PubMed] | + | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097/ PubMed] |
− | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https:// | + | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https://doi.org/10.1056/NEJMoa1913662 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31751012/ PubMed] |
− | #'''NEJ026:''' Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. [https:// | + | #'''NEJ026:''' Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. [https://doi.org/10.1016/S1470-2045(19)30035-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30975627/ PubMed] UMIN000017069 |
− | #''' | + | ##'''Update:''' Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Seike M, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. Epub 2021 Aug 26. [https://doi.org/10.1016/s2213-2600(21)00166-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34454653/ PubMed] |
− | #''' | + | #'''SOLAR:''' Kelly RJ, Shepherd FA, Krivoshik A, Jie F, Horn L. A phase 3, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1127-1133. Epub 2019 May 9. [https://doi.org/10.1093/annonc/mdz128 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31070709/ PubMed] [https://clinicaltrials.gov/study/NCT02588261 NCT02588261] |
+ | #'''RELAY:''' Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. [https://doi.org/10.1016/S1470-2045(19)30634-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31591063/ PubMed] [https://clinicaltrials.gov/study/NCT02411448 NCT02411448] | ||
+ | ##'''PRO analysis:''' Yoh K, Atagi S, Reck M, Garon EB, Ponce Aix S, Moro-Sibilot D, Winfree KB, Frimodt-Moller B, Zimmermann A, Visseren-Grul C, Nakagawa K; RELAY investigators. Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer. Curr Med Res Opin. 2020 Oct;36(10):1667-1675. Epub 2020 Aug 28. [https://doi.org/10.1080/03007995.2020.1808781 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32780643/ PubMed] | ||
+ | #'''ARTEMIS-CTONG1509:''' Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. Epub 2021 Aug 12. [https://doi.org/10.1016/j.ccell.2021.07.005 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34388377/ PubMed] [https://clinicaltrials.gov/study/NCT02759614 NCT02759614] | ||
+ | #'''BEVERLY:''' Piccirillo MC, Bonanno L, Garassino MC, Esposito G, Dazzi C, Cavanna L, Burgio MA, Rosetti F, Rizzato S, Morgillo F, Cinieri S, Veccia A, Papi M, Tonini G, Gebbia V, Ricciardi S, Pozzessere D, Ferro A, Proto C, Costanzo R, D'Arcangelo M, Proietto M, Gargiulo P, Di Liello R, Arenare L, De Marinis F, Crinò L, Ciardiello F, Normanno N, Gallo C, Perrone F, Gridelli C, Morabito A. Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial. J Thorac Oncol. 2022 Sep;17(9):1086-1097. Epub 2022 Jun 1. [https://doi.org/10.1016/j.jtho.2022.05.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35659580/ PubMed] [https://clinicaltrials.gov/study/NCT02633189 NCT02633189] | ||
==Erlotinib & Bevacizumab {{#subobject:6725f4|Regimen=1}}== | ==Erlotinib & Bevacizumab {{#subobject:6725f4|Regimen=1}}== | ||
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− | |||
− | |||
===Regimen {{#subobject:8ab85e|Variant=1}}=== | ===Regimen {{#subobject:8ab85e|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70381-X Seto et al. 2014 (JO25567)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-69-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2011-2012 | |2011-2012 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 16 vs 9. | + | | style="background-color:#1a9850" |Superior PFS<sup>1</sup> (primary endpoint)<br>Median PFS: 16.4 vs 9.8 mo<br>(HR 0.52, 95% CI 0.35-0.76)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 47.4 vs 47 mo<br>(HR 0.81, 95% CI 0.53-1.23) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(19)30035-X Saito et al. 2019 (NEJ026)] |
− | |2015-2016 | + | |2015-06-03 to 2016-08-31 |
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
− | | style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 16.9 vs 13.3 mo<br>(HR 0.61, 95% CI 0.42-0.88) | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 16.9 vs 13.3 mo<br>(HR 0.61, 95% CI 0.42-0.88)<br><br>Did not meet secondary endpoint of OS<sup>2</sup><br>Median OS: 50.7 vs 46.2 mo<br>(HR 1.01, 95% CI 0.68-1.49) |
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ccell.2021.07.005 Zhou et al. 2021 (ARTEMIS-CTONG1509)] | ||
+ | |2016-05 to 2017-07 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 17.9 vs 11.2 mo<br>(HR 0.55, 95% CI 0.41-0.73) | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.jtho.2022.05.008 Piccirillo et al. 2022 (BEVERLY)] | ||
+ | |2016-2019 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 15.4 vs 9.6 mo<br>(HR 0.66, 95% CI 0.47-0.92) | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy for JO25567 is based on the 2020 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for OS for NEJ026 is based on the 2021 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 21 | |
− | *[[Erlotinib (Tarceva)]] 150 mg PO once per day | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''JO25567:''' Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. [https://doi.org/10.1016/S1470-2045(14)70381-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25175099/ PubMed] JapicCTI-111390 | |
− | #'''JO25567:''' Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. [https:// | + | ##'''Update:''' Yamamoto N, Seto T, Nishio M, Goto K, Yamamoto N, Okamoto I, Yamanaka T, Tanaka M, Takahashi K, Fukuoka M. Erlotinib plus bevacizumab vs erlotinib monotherapy as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer: Survival follow-up results of the randomized JO25567 study. Lung Cancer. 2021 Jan;151:20-24. Epub 2020 Nov 20. [https://doi.org/10.1016/j.lungcan.2020.11.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33279874/ PubMed] |
− | #'''NEJ026:''' Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. [https:// | + | #'''NEJ026:''' Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. [https://doi.org/10.1016/S1470-2045(19)30035-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30975627/ PubMed] UMIN000017069 |
+ | ##'''Update:''' Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Seike M, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. Epub 2021 Aug 26. [https://doi.org/10.1016/s2213-2600(21)00166-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34454653/ PubMed] | ||
+ | #'''ARTEMIS-CTONG1509:''' Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. Epub 2021 Aug 12. [https://doi.org/10.1016/j.ccell.2021.07.005 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34388377/ PubMed] [https://clinicaltrials.gov/study/NCT02759614 NCT02759614] | ||
+ | #'''BEVERLY:''' Piccirillo MC, Bonanno L, Garassino MC, Esposito G, Dazzi C, Cavanna L, Burgio MA, Rosetti F, Rizzato S, Morgillo F, Cinieri S, Veccia A, Papi M, Tonini G, Gebbia V, Ricciardi S, Pozzessere D, Ferro A, Proto C, Costanzo R, D'Arcangelo M, Proietto M, Gargiulo P, Di Liello R, Arenare L, De Marinis F, Crinò L, Ciardiello F, Normanno N, Gallo C, Perrone F, Gridelli C, Morabito A. Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial. J Thorac Oncol. 2022 Sep;17(9):1086-1097. Epub 2022 Jun 1. [https://doi.org/10.1016/j.jtho.2022.05.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35659580/ PubMed] [https://clinicaltrials.gov/study/NCT02633189 NCT02633189] | ||
==Erlotinib & Ramucirumab {{#subobject:62bc24|Regimen=1}}== | ==Erlotinib & Ramucirumab {{#subobject:62bc24|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:8b926b|Variant=1}}=== | ===Regimen {{#subobject:8b926b|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 943: | Line 1,370: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(19)30634-5 Nakagawa et al. 2019 (RELAY)] |
− | |2016-2018 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-169-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2016-01-28 to 2018-02-01 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-esc) | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
− | | style="background-color:#1a9850" |Superior PFS <br>Median PFS: 19.4 | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 19.4 vs 12.4 mo<br>(HR 0.59, 95% CI 0.46-0.76) |
|- | |- | ||
|} | |} | ||
''Note: the FDA-recommended dose is only provided for ramucirumab.'' | ''Note: the FDA-recommended dose is only provided for ramucirumab.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 14 | |
− | *[[Erlotinib (Tarceva)]] 150 mg PO once per day | ||
*[[Ramucirumab (Cyramza)]] 10 mg/kg IV once on day 1 | *[[Ramucirumab (Cyramza)]] 10 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | #'''RELAY:''' Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. [https://doi.org/10.1016/S1470-2045(19)30634-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31591063/ PubMed] [https://clinicaltrials.gov/study/NCT02411448 NCT02411448] | ||
+ | ##'''PRO analysis:''' Yoh K, Atagi S, Reck M, Garon EB, Ponce Aix S, Moro-Sibilot D, Winfree KB, Frimodt-Moller B, Zimmermann A, Visseren-Grul C, Nakagawa K; RELAY investigators. Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer. Curr Med Res Opin. 2020 Oct;36(10):1667-1675. Epub 2020 Aug 28. [https://doi.org/10.1080/03007995.2020.1808781 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32780643/ PubMed] | ||
+ | ==Furmonertinib monotherapy {{#subobject:fu9b98|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:60ckl1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/s2213-2600(22)00168-0 Shi et al. 2022 (FURLONG)] | ||
+ | |2019-05-30 to 2019-12-05 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 20.8 vs 11.1 mo<br>(HR 0.44, 95% CI 0.34-0.58) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *FURLONG: EGFR exon 19 deletion or EGFR p.L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Furmonertinib (Ivesa)]] 80 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''FURLONG:''' Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, Liu J, Cao L, Cheng Y, Zhao H, Zhang S, Zang A, Cui J, Feng J, Yang N, Liu F, Jiang Y, Gu C; FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-1028. Epub 2022 Jun 2. [https://doi.org/10.1016/s2213-2600(22)00168-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35662408/ PubMed] [https://clinicaltrials.gov/study/NCT03787992 NCT03787992] | |
− | #''' | ||
==GCP {{#subobject:fb3ac8|Regimen=1}}== | ==GCP {{#subobject:fb3ac8|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
GCP: '''<u>G</u>'''efitinib, '''<u>C</u>'''arboplatin, '''<u>P</u>'''emetrexed | GCP: '''<u>G</u>'''efitinib, '''<u>C</u>'''arboplatin, '''<u>P</u>'''emetrexed | ||
− | ===Regimen variant #1, 4 cycles {{#subobject:ugbe4f|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 4 cycles of carboplatin {{#subobject:ugbe4f|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 985: | Line 1,440: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 16 vs 8 mo<br>(HR 0.51, 95% CI 0.39-0.66)<br><br>Superior OS (secondary endpoint)<br>Median OS: NYR vs 17 mo<br>(HR 0.45, 95% CI 0.31-0.65) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Gefitinib (Iressa)]] 250 mg PO once per day on days 1 to 21 | |
− | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Carboplatin (Paraplatin)]] as follows: | |
− | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | + | **Cycles 1 to 4: AUC 5 IV once on day 1 |
*[[Pemetrexed (Alimta)]] 500 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 cycles''' | |
− | '''21-day | + | </div></div><br> |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2, 6 cycles of carboplatin {{#subobject:5134e4f|Variant=1}}=== | |
− | |||
− | |||
− | ===Regimen variant #2, 6 cycles {{#subobject:5134e4f|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 1,014: | Line 1,465: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 50.9 vs 38.8 mo<br>(HR 0.72, 95% CI 0.55-0.95) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Gefitinib (Iressa)]] 250 mg PO once per day | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Carboplatin (Paraplatin)]] as follows: | |
− | *[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1 | + | **Cycles 1 to 6: AUC 5 IV once on day 1 |
*[[Pemetrexed (Alimta)]] 500 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 up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | #'''NEJ009:''' Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. [https://doi.org/10.1200/JCO.19.01488 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31682542/ PubMed] UMIN000006340 | |
− | #'''NEJ009:''' Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. [https://doi.org/10.1200/JCO.19.01488 link to original article] ''' | + | #Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. [https://doi.org/10.1200/JCO.19.01154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31411950/ PubMed] CTRI/2016/08/007149 |
− | #Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. [https://doi.org/10.1200/JCO.19.01154 link to original article] ''' | ||
− | |||
==Gefitinib monotherapy {{#subobject:fb3998|Regimen=1}}== | ==Gefitinib monotherapy {{#subobject:fb3998|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:604e4f|Variant=1}}=== | ===Regimen {{#subobject:604e4f|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,048: | Line 1,489: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(09)70364-X Mitsudomi et al. 2009 (WJTOG3405)] |
|2006-2009 | |2006-2009 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]] | |[[#Cisplatin_.26_Docetaxel_.28DC.29|Cisplatin & Docetaxel]] | ||
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 9.2 vs 6.3 mo<br>(HR 0.49, 95% CI 0.34-0.71) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa0909530 Maemondo et al. 2010 (NEJ002)] |
|2006-2009 | |2006-2009 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | |[[#Carboplatin_.26_Paclitaxel_.28CP.29|Carboplatin & Paclitaxel]] | ||
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS 10.8 vs 5.4 mo<br>(HR 0.30, 95% CI 0.22-0.41) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.8 vs 5.4 mo<br>(HR 0.30, 95% CI 0.22-0.41) |
|- | |- | ||
|[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)] | |[https://doi.org/10.1200/jco.2015.63.4154 Urata et al. 2016 (WJOG 5108L)] | ||
|2009-2012 | |2009-2012 | ||
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS | | style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS | ||
Line 1,075: | Line 1,516: | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Erlotinib_monotherapy|Erlotinib]] | |[[#Erlotinib_monotherapy|Erlotinib]] | ||
− | | style="background-color:# | + | | style="background-color:#fee08b" |Might have inferior PFS |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ Douillard et al. 2014 (IFUM)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ Douillard et al. 2014 (IFUM)] | ||
|2010-2012 | |2010-2012 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 4 (RT) |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#b3b3b3" |ORR: 70% (95% CI: 60.5–78) | | style="background-color:#b3b3b3" |ORR: 70% (95% CI: 60.5–78) | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30033-X Park et al. 2016 (LUX-Lung 7)] |
|2011-2013 | |2011-2013 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#Afatinib_monotherapy|Afatinib]] | |[[#Afatinib_monotherapy|Afatinib]] | ||
− | | style="background-color:# | + | | style="background-color:#d73027" |Inferior PFS |
|- | |- | ||
|[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | |[https://doi.org/10.1200/JCO.19.01488 Hosomi et al. 2019 (NEJ009)] | ||
Line 1,093: | Line 1,534: | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#GCP|GCP]] | |[[#GCP|GCP]] | ||
− | | style="background-color:# | + | | style="background-color:#d73027" |Inferior OS |
|- | |- | ||
|[https://doi.org/10.1200/jco.2016.66.9218 Cheng et al. 2016 (JMIT)] | |[https://doi.org/10.1200/jco.2016.66.9218 Cheng et al. 2016 (JMIT)] | ||
|2012-2013 | |2012-2013 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#Gefitinib_.26_Pemetrexed|P+G]] | |[[#Gefitinib_.26_Pemetrexed|P+G]] | ||
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
Line 1,104: | Line 1,545: | ||
|2012-2016 | |2012-2016 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |[[#Carboplatin_. | + | |[[#Carboplatin_.26_Pemetrexed_2|Carboplatin & Pemetrexed]] |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.4 vs 5.6 mo<br>(HR 0.66, 95% CI 0.51-0.85) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(17)30608-3 Wu et al. 2017 (ARCHER 1050)] |
|2013-2015 | |2013-2015 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 1,113: | Line 1,554: | ||
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] |
|2014-2016 | |2014-2016 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 1,124: | Line 1,565: | ||
|[[#GCP|GCP]] | |[[#GCP|GCP]] | ||
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.jtho.2021.05.006 Zhao et al. 2021 (CTONG1706)] | ||
+ | |2017-08 to 2018-12 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Apatinib_.26_Gefitinib|Apatinib & Gefitinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509093/ Lu et al. 2022 (AENEAS)] | ||
+ | |2018-11-30 to 2019-09-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Aumolertinib_monotherapy|Aumolertinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/s2213-2600(22)00168-0 Shi et al. 2022 (FURLONG)] | ||
+ | |2019-05-30 to 2019-12-05 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Furmonertinib_monotherapy|Furmonertinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.23.00515 Cho et al. 2023 (LASER301)] | ||
+ | |2020-02 to 2021-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Lazertinib_monotherapy|Lazertinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
Line 1,129: | Line 1,594: | ||
''<sup>2</sup>Reported efficacy for FLAURA is based on the 2019 update.''<br> | ''<sup>2</sup>Reported efficacy for FLAURA is based on the 2019 update.''<br> | ||
''Note: these are all trials restricted to EGFR-mutated lung cancer, with the exception of WJOG 5108L, which nevertheless had 72% EGFR-mutated patients.'' | ''Note: these are all trials restricted to EGFR-mutated lung cancer, with the exception of WJOG 5108L, which nevertheless had 72% EGFR-mutated patients.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *FURLONG: EGFR exon 19 deletion or EGFR p.L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Gefitinib (Iressa)]] 250 mg PO once per day | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''WJTOG3405:''' Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. [https://doi.org/10.1016/S1470-2045(09)70364-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20022809/ PubMed] UMIN000000539 | |
− | #'''WJTOG3405:''' Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. [https:// | + | ##'''Update:''' Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. [https://doi.org/10.1093/annonc/mdz399 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31553438/ PubMed] |
− | ##'''Update:''' Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. [https://doi.org/10.1093/annonc/mdz399 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31553438 PubMed] | + | #'''NEJ002:''' Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. [https://doi.org/10.1056/NEJMoa0909530 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20573926/ PubMed] UMIN000000376 |
− | #'''NEJ002:''' Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. [https:// | + | ##'''HRQoL analysis:''' Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. [https://doi.org/10.1634/theoncologist.2011-0426 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380886/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22581822/ PubMed] |
− | ##'''HRQoL analysis:''' Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. [ | + | ##'''Update:''' Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. [https://doi.org/10.1093/annonc/mds214 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22967997/ PubMed] |
− | ##'''Update:''' Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. [https://doi.org/10.1093/annonc/mds214 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22967997 PubMed] | + | #'''IFUM:''' Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. Epub 2013 Nov 21. [https://doi.org/10.1038/bjc.2013.721 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24263064/ PubMed] [https://clinicaltrials.gov/study/NCT01203917 NCT01203917] |
− | #'''IFUM:''' Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. Epub 2013 Nov 21. [https:// | + | #'''LUX-Lung 7:''' Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [https://doi.org/10.1016/S1470-2045(16)30033-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27083334/ PubMed] [https://clinicaltrials.gov/study/NCT01466660 NCT01466660] |
− | #'''LUX-Lung 7:''' Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [https:// | + | #'''WJOG 5108L:''' Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.63.4154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27022112/ PubMed] UMIN000002014 |
− | #'''WJOG 5108L:''' Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [https://doi.org/10.1200/jco.2015.63.4154 link to original article] ''' | + | #'''JMIT:''' Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [https://doi.org/10.1200/jco.2016.66.9218 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27507876/ PubMed] [https://clinicaltrials.gov/study/NCT01469000 NCT01469000] |
− | #'''JMIT:''' Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [https://doi.org/10.1200/jco.2016.66.9218 link to original article] ''' | + | #'''CTONG 0901:''' Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. [https://doi.org/10.1038/bjc.2016.456 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344291/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28103612/ PubMed] [https://clinicaltrials.gov/study/NCT01024413 NCT01024413] |
− | #'''CTONG 0901:''' Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. [https://doi.org/10.1038/bjc.2016.456 link to original article] ''' | + | #Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. [https://doi.org/10.1136/esmoopen-2017-000168 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519810/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28761735/ PubMed] |
− | #Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. [https:// | + | #'''ARCHER 1050:''' Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. [https://doi.org/10.1016/S1470-2045(17)30608-3 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28958502/ PubMed] [https://clinicaltrials.gov/study/NCT01774721 NCT01774721] |
− | #'''ARCHER 1050:''' Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. [https:// | + | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. [https://doi.org/10.1200/JCO.2018.78.7994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29864379/ PubMed] |
− | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. [https://doi.org/10.1200/JCO.2018.78.7994 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29864379 PubMed] | + | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. [https://doi.org/10.1007/s40265-020-01441-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7932969/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33331989/ PubMed] |
− | ##'''Update:''' Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. [https://doi.org/10.1007/s40265-020-01441-6 link to original article] [ | + | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https://doi.org/10.1056/NEJMoa1713137 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29151359/ PubMed] [https://clinicaltrials.gov/study/NCT02296125 NCT02296125] |
− | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https:// | + | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097/ PubMed] |
− | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097 PubMed] | + | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https://doi.org/10.1056/NEJMoa1913662 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31751012/ PubMed] |
− | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https:// | + | #'''NEJ009:''' Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. [https://doi.org/10.1200/JCO.19.01488 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31682542/ PubMed] UMIN000006340 |
− | #'''NEJ009:''' Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. [https://doi.org/10.1200/JCO.19.01488 link to original article] ''' | + | #Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. [https://doi.org/10.1200/JCO.19.01154 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31411950/ PubMed] CTRI/2016/08/007149 |
− | #Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. [https://doi.org/10.1200/JCO.19.01154 link to original article] ''' | + | #'''CTONG1706:''' Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q, Wu G, Jiang O, Du X, Liu J, Gu W, Hou Z, Wang Q, Zheng R, Zhou X, Zhang L. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. Epub 2021 May 24. [https://doi.org/10.1016/j.jtho.2021.05.006 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/34033974/ PubMed] [https://clinicaltrials.gov/study/NCT02824458 NCT02824458] |
+ | #'''AENEAS:''' Lu S, Dong X, Jian H, Chen J, Chen G, Sun Y, Ji Y, Wang Z, Shi J, Lu J, Chen S, Lv D, Zhang G, Liu C, Li J, Yu X, Lin Z, Yu Z, Wang Z, Cui J, Xu X, Fang J, Feng J, Xu Z, Ma R, Hu J, Yang N, Zhou X, Wu X, Hu C, Zhang Z, Lu Y, Hu Y, Jiang L, Wang Q, Guo R, Zhou J, Li B, Hu C, Tong W, Zhang H, Ma L, Chen Y, Jie Z, Yao Y, Zhang L, Jie W, Li W, Xiong J, Ye X, Duan J, Yang H, Sun M, Sun C, Wei H, Li C, Ali SM, Miller VA, Wu Q. AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations. J Clin Oncol. 2022 Sep 20;40(27):3162-3171. Epub 2022 May 17. [https://doi.org/10.1200/jco.21.02641 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9509093/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35580297/ PubMed] [https://clinicaltrials.gov/study/NCT03849768 NCT03849768] | ||
+ | #'''FURLONG:''' Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, Liu J, Cao L, Cheng Y, Zhao H, Zhang S, Zang A, Cui J, Feng J, Yang N, Liu F, Jiang Y, Gu C; FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-1028. Epub 2022 Jun 2. [https://doi.org/10.1016/s2213-2600(22)00168-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/35662408/ PubMed] [https://clinicaltrials.gov/study/NCT03787992 NCT03787992] | ||
+ | #'''LASER301:''' Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. Epub 2023 Jun 28. [https://doi.org/10.1200/jco.23.00515 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37379502/ PubMed] [https://clinicaltrials.gov/study/NCT04248829 NCT04248829] | ||
==Gefitinib & Pemetrexed {{#subobject:bbe840|Regimen=1}}== | ==Gefitinib & Pemetrexed {{#subobject:bbe840|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
P+G: '''<u>P</u>'''emetrexed and '''<u>G</u>'''efitinib | P+G: '''<u>P</u>'''emetrexed and '''<u>G</u>'''efitinib | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5281f8|Variant=1}}=== | ===Regimen {{#subobject:5281f8|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 1,173: | Line 1,641: | ||
|[https://doi.org/10.1200/jco.2016.66.9218 Cheng et al. 2016 (JMIT)] | |[https://doi.org/10.1200/jco.2016.66.9218 Cheng et al. 2016 (JMIT)] | ||
|2012-2013 | |2012-2013 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
|[[#Gefitinib_monotherapy_2|Gefitinib]] | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
− | | style="background-color:#91cf60" |Seems to have superior PFS | + | | style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Gefitinib (Iressa)]] 250 mg PO once per day on days 1 to 21 | |
− | *[[Gefitinib (Iressa)]] 250 mg PO once per day | ||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[Pemetrexed (Alimta)]] 500 mg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''JMIT:''' Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [https://doi.org/10.1200/jco.2016.66.9218 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27507876/ PubMed] [https://clinicaltrials.gov/study/NCT01469000 NCT01469000] | |
− | #'''JMIT:''' Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [https://doi.org/10.1200/jco.2016.66.9218 link to original article] ''' | ||
− | |||
==Icotinib monotherapy {{#subobject:9720a1|Regimen=1}}== | ==Icotinib monotherapy {{#subobject:9720a1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:d7253b|Variant=1}}=== | ===Regimen {{#subobject:d7253b|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 1,206: | Line 1,666: | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | |[https://doi.org/10.1093/annonc/mdx359 Shi et al. 2017 (CONVINCE)] | ||
− | |2013-2014 | + | |2013-01 to 2014-08 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |[[#Cisplatin_. | + | |[[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] x 4, then [[#Pemetrexed_monotherapy_2|Pemetrexed]] maintenance |
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.2 vs 7.9 mo<br>(HR 0.61, 95% CI 0.43-0.87) |
+ | |- | ||
+ | |[https://doi.org/10.1016/s2213-2600(23)00183-2 Lu et al. 2023] | ||
+ | |2019-12-24 to 2020-12-18 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Befotertinib_monotherapy_777|Befotertinib]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.'' | + | ''Note: this drug is only approved in China; eligible patients in CONVINCE had stage IIIB/IV lung adenocarcinoma.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
− | *EGFR exon 19 or 21 mutations | + | *CONVINCE: EGFR exon 19 or 21 mutations |
+ | *Lu et al. 2023: EGFR exon 19 deletions or exon 21 Leu858Arg mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Icotinib (Conmana)]] 125 mg PO three times per day | *[[Icotinib (Conmana)]] 125 mg PO three times per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
+ | #'''CONVINCE:''' Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. [https://doi.org/10.1093/annonc/mdx359 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28945850/ PubMed] [https://clinicaltrials.gov/study/NCT01719536 NCT01719536] | ||
+ | #Lu S, Zhou J, Jian H, Wu L, Cheng Y, Fan Y, Fang J, Chen G, Zhang Z, Lv D, Jiang L, Wu R, Jin X, Zhang X, Zhang J, Xie C, Sun G, Huang D, Cui J, Guo R, Han Z, Chen Z, Liang J, Zhuang W, Hu X, Zang A, Zhang Y, Cang S, Lan Y, Chen X, Liu L, Li X, Chen J, Ma R, Guo Y, Sun P, Tian P, Pan Y, Liu Z, Cao P, Ding L, Wang Y, Yuan X, Wu P. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respir Med. 2023 Oct;11(10):905-915. Epub 2023 May 24. [https://doi.org/10.1016/s2213-2600(23)00183-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37244266/ PubMed] [https://clinicaltrials.gov/study/NCT04206072 NCT04206072] | ||
− | # | + | ==Lazertinib monotherapy {{#subobject:figj98|Regimen=1}}== |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | = | + | ===Regimen {{#subobject:6igicj|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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.23.00515 Cho et al. 2023 (LASER301)] | ||
+ | |2020-02 to 2021-09 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#Gefitinib_monotherapy_2|Gefitinib]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 20.6 vs 9.7 mo<br>(HR 0.45, 95% CI 0.34-0.58) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Lazertinib (Leclaza)]] 240 mg PO once per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''LASER301:''' Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. Epub 2023 Jun 28. [https://doi.org/10.1200/jco.23.00515 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37379502/ PubMed] [https://clinicaltrials.gov/study/NCT04248829 NCT04248829] | ||
+ | ==Osimertinib monotherapy {{#subobject:e73636|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:b7880f|Variant=1}}=== | ===Regimen {{#subobject:b7880f|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,237: | Line 1,726: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1713137 Soria et al. 2017 (FLAURA)] |
|2014-2016 | |2014-2016 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
− | | | + | |1a. [[#Erlotinib_monotherapy|Erlotinib]]<br>1b. [[#Gefitinib_monotherapy|Gefitinib]] |
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 18.9 vs 10.2 mo<br>(HR 0.46, 95% CI 0.37-0.57)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 38.6 vs 31.8 mo<br>(HR 0.80, 95% CI 0.64-1.00) |
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2306434 Planchard et al. 2023 (FLAURA2)] | ||
+ | |2020-06-01 to 2021-12-22 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Osimertinib.2C_Pemetrexed|Carboplatin, Osimertinib, Pemetrexed]]<br>1b. [[#Cisplatin.2C_Osimertinib.2C_Pemetrexed|Cisplatin, Osimertinib, Pemetrexed]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | ''<sup>1</sup>Reported efficacy is based on the 2019 update.''<br> | + | ''<sup>1</sup>Reported efficacy for FLAURA is based on the 2019 update.''<br> |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*EGFR exon 19 deletion or p.L858R mutation | *EGFR exon 19 deletion or p.L858R mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Osimertinib (Tagrisso)]] 80 mg PO once per day | *[[Osimertinib (Tagrisso)]] 80 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https://doi.org/10.1056/NEJMoa1713137 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29151359/ PubMed] [https://clinicaltrials.gov/study/NCT02296125 NCT02296125] | |
− | #'''FLAURA:''' Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. [https:// | + | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097/ PubMed] |
− | ##'''Subgroup analysis:''' Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. [https://doi.org/10.1200/JCO.2018.78.3118 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30153097 PubMed] | + | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https://doi.org/10.1056/NEJMoa1913662 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31751012/ PubMed] |
− | ##'''Update:''' Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. [https:// | + | #'''FLAURA2:''' Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. [https://doi.org/10.1056/nejmoa2306434 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37937763/ PubMed] [https://clinicaltrials.gov/study/NCT04035486 NCT04035486] |
+ | #'''ECOG-ACRIN EA5182:''' [https://clinicaltrials.gov/study/NCT04181060 NCT04181060] | ||
+ | #'''MARIPOSA:''' [https://clinicaltrials.gov/study/NCT04487080 NCT04487080] | ||
=Advanced or metastatic disease, EGFR inhibitor-exposed= | =Advanced or metastatic disease, EGFR inhibitor-exposed= | ||
− | == | + | ==ABCP {{#subobject:ee72af|Regimen=1}}== |
− | {| class="wikitable" style=" | + | ABCP: '''<u>A</u>'''tezolizumab, '''<u>B</u>'''evacizumab, '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, 4 cycles then maintenance {{#subobject:9088c6|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/pmc11095857/ Park et al. 2023 (ATTLAS)] | ||
+ | |2019-08-27 to 2022-03-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]]<br>1b. [[#Cisplatin_.26_Pemetrexed_3|Cisplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.48 vs 5.62 mo<br>(HR 0.62, 95% CI 0.45-0.86) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Immunotherapy==== | ||
+ | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 5 or 5.5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 4: 175 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, 6 cycles then maintenance {{#subobject:99ed77|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/pmc11095857/ Park et al. 2023 (ATTLAS)] | ||
+ | |2019-08-27 to 2022-03-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1a. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]]<br>1b. [[#Cisplatin_.26_Pemetrexed_3|Cisplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.48 vs 5.62 mo<br>(HR 0.62, 95% CI 0.45-0.86) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Immunotherapy==== | ||
+ | *[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1 | ||
+ | ====Targeted therapy==== | ||
+ | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6: AUC 5 or 5.5 IV once on day 1 | ||
+ | *[[Paclitaxel (Taxol)]] as follows: | ||
+ | **Cycles 1 to 6: 175 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''ATTLAS:''' Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. [https://doi.org/10.1200/jco.23.01891 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11095857/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37861993/ PubMed] [https://clinicaltrials.gov/study/NCT03991403 NCT03991403] | ||
+ | |||
+ | ==Afatinib monotherapy {{#subobject:1a2d3b|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:f109f9|Variant=1}}=== | ===Regimen {{#subobject:f109f9|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
!style="width: 25%"|Study | !style="width: 25%"|Study | ||
− | !style="width: 25%"| | + | !style="width: 25%"|Dates of enrollment |
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
Line 1,279: | Line 1,843: | ||
|[https://doi.org/10.1200/jco.2012.45.0981 Katakami et al. 2013 (LUX-Lung 4)] | |[https://doi.org/10.1200/jco.2012.45.0981 Katakami et al. 2013 (LUX-Lung 4)] | ||
|2009-2011 | |2009-2011 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
| style="background-color:#6e016b; color:white " |ORR: 8% (95% CI: 3-18) | | 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 | + | ''Note: In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression while receiving erlotinib and/or gefitinib and had received one or two previous lines of chemotherapy, including at least one platinum-based regimen | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Afatinib (Gilotrif)]] 50 mg PO once per day, taken at least 1 hour before eating food | |
− | *[[Afatinib (Gilotrif)]] 50 mg PO once per day, | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23816963/ PubMed] [https://clinicaltrials.gov/study/NCT00711594 NCT00711594] | |
− | #'''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] ''' | ||
==Afatinib & Bevacizumab {{#subobject:85g7gb|Regimen=1}}== | ==Afatinib & Bevacizumab {{#subobject:85g7gb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:u151f9|Variant=1}}=== | ===Regimen {{#subobject:u151f9|Variant=1}}=== | ||
{| class="wikitable" style="width: 60%; text-align:center;" | {| class="wikitable" style="width: 60%; text-align:center;" | ||
! style="width: 33%" |Study | ! style="width: 33%" |Study | ||
− | ! style="width: 33%" | | + | ! style="width: 33%" |Dates of enrollment |
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.31678 Hata et al. 2018 (ABC Study)] |
|2014-2017 | |2014-2017 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Afatinib (Gilotrif)]] 30 mg PO once per day on days 1 to 21 | |
− | *[[Afatinib (Gilotrif)]] 30 mg PO once per day | ||
*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ABC Study:''' Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, Morita S, Negoro S; Hanshin Oncology Group F. Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study). Cancer. 2018 Oct 1;124(19):3830-3838. Epub 2018 Sep 7. [https://doi.org/10.1002/cncr.31678 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30192383/ PubMed] UMIN000014710 | |
− | #'''ABC Study:''' Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, Morita S, Negoro S; Hanshin Oncology Group F. Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study). Cancer. 2018 Oct 1;124(19):3830-3838. Epub 2018 Sep 7. [https:// | ||
− | |||
==Afatinib & Cetuximab {{#subobject:1a37gb|Regimen=1}}== | ==Afatinib & Cetuximab {{#subobject:1a37gb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:f171f9|Variant=1}}=== | ===Regimen {{#subobject:f171f9|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: | + | {| class="wikitable sortable" style="width: 80%; text-align:center;" |
!style="width: 25%"|Study | !style="width: 25%"|Study | ||
− | !style="width: 25%"| | + | !style="width: 25%"|Dates of enrollment |
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]] | ||
Line 1,334: | Line 1,891: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155006/ Janjigian et al. 2014 (BI 1200.71)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155006/ Janjigian et al. 2014 (BI 1200.71)] | ||
|2010-2013 | |2010-2013 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1b |
|ORR: 29% | |ORR: 29% | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Afatinib (Gilotrif)]] 40 mg PO once per day on days 1 to 14 | |
− | *[[Afatinib (Gilotrif)]] 40 mg PO once per day | ||
*[[Cetuximab (Erbitux)]] 500 mg IV once on day 1 | *[[Cetuximab (Erbitux)]] 500 mg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''BI 1200.71:''' Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. Epub 2014 Jul 29. [https://cancerdiscovery.aacrjournals.org/content/4/9/1036.short link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155006/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25074459/ PubMed] [https://clinicaltrials.gov/study/NCT01090011 NCT01090011] | ||
+ | ==Carboplatin & Pemetrexed {{#subobject:60cb1d|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, AUC 5 x 4 with pemetrexed maintenance {{#subobject:ycj37d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/PMC11095864/ Mok et al. 2024 (CheckMate 722)] | ||
+ | |2017-03 to 2020-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Pemetrexed.2C_Nivolumab_999|Carboplatin, Pemetrexed, Nivolumab]]<br>1b. [[#Cisplatin.2C_Pemetrexed.2C_Nivolumab_999|Cisplatin, Pemetrexed, Nivolumab]] | ||
+ | | style="background-color:#fee08b" |Might have inferior PFS (primary endpoint)<br>Median PFS: 5.4 vs 5.6 mo<br>(HR 1.33, 95% CI 1.00-1.79) | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11095857/ Park et al. 2023 (ATTLAS)] | ||
+ | |2019-08-27 to 2022-03-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ABCP|ABCP]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.annonc.2023.10.117 Passaro et al. 2023 (MARIPOSA-2)] | ||
+ | |2021-12 to 2023-04 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1. [[#Carboplatin.2C_Pemetrexed.2C_Amivantamab_2|Carboplatin, Pemetrexed, Amivantamab]]<br>2. [[#Carboplatin.2C_Lazertinib.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Lazertinib, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |[https://clinicaltrials.gov/study/NCT05338970 Awaiting publication (HERTHENA-Lung02)] | ||
+ | |2022-ongoing | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Patritumab_deruxtecan_monotherapy|Patritumab-DXd]] | ||
+ | | style="background-color:#d3d3d3" |TBD if different primary endpoint of PFS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this was the lower bound of carboplatin dosing in CheckMate 722.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *MARIPOSA-2: Progression after osimertinib | ||
+ | *HERTHENA-Lung02: Progression after first-line EGFR TKI therapy | ||
+ | *ATTLAS: Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <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 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, AUC 5 x 6 with pemetrexed maintenance {{#subobject:yc567d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/pmc11095857/ Park et al. 2023 (ATTLAS)] | ||
+ | |2019-08-27 to 2022-03-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ABCP|ABCP]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 6: AUC 5 IV once on day 1 | ||
+ | *[[Pemetrexed (Alimta)]] 500 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 #3, AUC 6 x 4 with pemetrexed maintenance {{#subobject:ycj36c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/PMC11095864/ Mok et al. 2024 (CheckMate 722)] | ||
+ | |2017-03 to 2020-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Pemetrexed.2C_Nivolumab_999|Carboplatin, Pemetrexed, Nivolumab]]<br>1b. [[#Cisplatin.2C_Pemetrexed.2C_Nivolumab_999|Cisplatin, Pemetrexed, Nivolumab]] | ||
+ | | style="background-color:#fee08b" |Might have inferior PFS (primary endpoint)<br>Median PFS: 5.4 vs 5.6 mo<br>(HR 1.33, 95% CI 1.00-1.79) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: this was the upper bound of carboplatin dosing in CheckMate 722.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Carboplatin (Paraplatin)]] as follows: | ||
+ | **Cycles 1 to 4: AUC 6 IV once on day 1 | ||
+ | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''MARIPOSA-2:''' Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. [https://doi.org/10.1016/j.annonc.2023.10.117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37879444/ PubMed] [https://clinicaltrials.gov/study/NCT04988295 NCT04988295] | ||
+ | #'''CheckMate 722:''' Mok T, Nakagawa K, Park K, Ohe Y, Girard N, Kim HR, Wu YL, Gainor J, Lee SH, Chiu CH, Kim SW, Yang CT, Wu CL, Wu L, Lin MC, Samol J, Ichikado K, Wang M, Zhang X, Sylvester J, Li S, Forslund A, Yang JC. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722. J Clin Oncol. 2024 Apr 10;42(11):1252-1264. Epub 2024 Jan 22. [https://doi.org/10.1200/jco.23.01017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095864/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38252907/ PubMed] [https://clinicaltrials.gov/study/NCT02864251 NCT02864251] | ||
+ | #'''ATTLAS:''' Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. [https://doi.org/10.1200/jco.23.01891 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11095857/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37861993/ PubMed] [https://clinicaltrials.gov/study/NCT03991403 NCT03991403] | ||
+ | #'''HERTHENA-Lung02:''' [https://clinicaltrials.gov/study/NCT05338970 NCT05338970] | ||
+ | ==Carboplatin, Pemetrexed, Amivantamab {{#subobject:7uhr74|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, lower-dose amivantamab {{#subobject:a24chd|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/j.annonc.2023.10.117 Passaro et al. 2023 (MARIPOSA-2)] | ||
+ | |rowspan=2|2021-12 to 2023-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.48, 95% CI 0.36-0.64) | ||
+ | |- | ||
+ | |2. [[#Carboplatin.2C_Lazertinib.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Lazertinib, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d3d3d3" |Not formally compared | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing less than 80 kg.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1400 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 1750 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, higher-dose amivantamab {{#subobject:15c37d|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/j.annonc.2023.10.117 Passaro et al. 2023 (MARIPOSA-2)] | ||
+ | |rowspan=2|2021-12 to 2023-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 6.3 vs 4.2 mo<br>(HR 0.48, 95% CI 0.36-0.64) | ||
+ | |- | ||
+ | |2. [[#Carboplatin.2C_Lazertinib.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Lazertinib, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d3d3d3" |Not formally compared | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing 80 kg or more.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1750 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 2100 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''MARIPOSA-2:''' Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. [https://doi.org/10.1016/j.annonc.2023.10.117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37879444/ PubMed] [https://clinicaltrials.gov/study/NCT04988295 NCT04988295] | ||
+ | ==Carboplatin, Lazertinib, Pemetrexed, Amivantamab {{#subobject:7laz74|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #1, lower-dose amivantamab {{#subobject:alzdcd|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/j.annonc.2023.10.117 Passaro et al. 2023 (MARIPOSA-2)] | ||
+ | |rowspan=2|2021-12 to 2023-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.3 vs 4.2 mo<br>(HR 0.44, 95% CI 0.35-0.56) | ||
+ | |- | ||
+ | |2. [[#Carboplatin.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d3d3d3" |Not formally compared | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing less than 80 kg. Due to excess toxicity in this arm, the lazertinib was not started until cycle 5, after a protocol modification.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1400 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 1750 mg IV once on day 1 | ||
+ | *[[Lazertinib (Leclaza)]] as follows: | ||
+ | **Cycle 5 onwards: 240 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, higher-dose amivantamab {{#subobject:1laozd|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/j.annonc.2023.10.117 Passaro et al. 2023 (MARIPOSA-2)] | ||
+ | |rowspan=2|2021-12 to 2023-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |1. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]] | ||
+ | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 8.3 vs 4.2 mo<br>(HR 0.44, 95% CI 0.35-0.56) | ||
+ | |- | ||
+ | |2. [[#Carboplatin.2C_Pemetrexed.2C_Amivantamab|Carboplatin, Pemetrexed, Amivantamab]] | ||
+ | | style="background-color:#d3d3d3" |Not formally compared | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: This amivantamab dosage was for patients weighing 80 kg or more. Due to excess toxicity in this arm, the lazertinib was not started until cycle 5, after a protocol modification.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR exon 19 deletion or p.L858R | ||
+ | </div> | ||
+ | <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==== | ||
+ | *[[Amivantamab (Rybrevant)]] as follows: | ||
+ | **Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15 | ||
+ | **Cycle 2: 1750 mg IV once on day 1 | ||
+ | **Cycle 3 onwards: 2100 mg IV once on day 1 | ||
+ | *[[Lazertinib (Leclaza)]] as follows: | ||
+ | **Cycle 5 onwards: 240 mg PO once per day on days 1 to 21 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''MARIPOSA-2:''' Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. [https://doi.org/10.1016/j.annonc.2023.10.117 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37879444/ PubMed] [https://clinicaltrials.gov/study/NCT04988295 NCT04988295] | |
− | #''' | ||
==Cisplatin & Pemetrexed {{#subobject:26acke|Regimen=1}}== | ==Cisplatin & Pemetrexed {{#subobject:26acke|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 70/500 x 4 with pemetrexed maintenance {{#subobject:7d7821|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/pmc11095857/ Park et al. 2023 (ATTLAS)] | ||
+ | |2019-08-27 to 2022-03-11 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ABCP|ABCP]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#fdcdac"> |
+ | ====Prior treatment criteria==== | ||
+ | *Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 4: 70 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 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #2, 70/500 x 6 with pemetrexed maintenance {{#subobject:766821|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11095857/ Park et al. 2023 (ATTLAS)] |
− | |2012-2013 | + | |2019-08-27 to 2022-03-11 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ABCP|ABCP]] | ||
+ | | style="background-color:#d73027" |Inferior PFS | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *Progression or intolerance to one or more EGFR TKIs | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 6: 70 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 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #3, 75/500, limited duration {{#subobject:7dcacb1|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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(15)00121-7 Soria et al. 2015 (IMPRESS)] | ||
+ | |2012-03-29 to 2013-12-20 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |Cisplatin, Pemetrexed, Gefitinib | + | |[[Stub#Cisplatin.2C_Pemetrexed.2C_Gefitinib|Cisplatin, Pemetrexed, Gefitinib]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *Progression after first-line gefitinib | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR mutation positive | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*(as described in Scagliotti et al. 2008): | *(as described in Scagliotti et al. 2008): | ||
− | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to | + | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to pemetrexed |
*[[Folic acid (Folate)]] 1 mg PO once per day | *[[Folic acid (Folate)]] 1 mg PO once per day | ||
− | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for | + | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for pemetrexed." |
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #4, 75/500 x 4 with pem maintenance {{#subobject:7dcb21|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates 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/PMC11095864/ Mok et al. 2024 (CheckMate 722)] | ||
+ | |2017-03 to 2020-06 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#Carboplatin.2C_Pemetrexed.2C_Nivolumab_999|Carboplatin, Pemetrexed, Nivolumab]]<br>1b. [[#Cisplatin.2C_Pemetrexed.2C_Nivolumab_999|Cisplatin, Pemetrexed, Nivolumab]] | ||
+ | | style="background-color:#fee08b" |Might have inferior PFS (primary endpoint)<br>Median PFS: 5.4 vs 5.6 mo<br>(HR 1.33, 95% CI 1.00-1.79) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cisplatin (Platinol)]] as follows: | ||
+ | **Cycles 1 to 4: 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 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''IMPRESS:''' Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. Epub 2015 Jul 6. [https://doi.org/10.1016/S1470-2045(15)00121-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26159065/ PubMed] [https://clinicaltrials.gov/study/NCT01544179 NCT01544179] | |
− | #'''IMPRESS:''' Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. Epub 2015 Jul 6. [https:// | + | ##'''Update:''' Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Shi X, Rukazenkov Y, Haddad V, Thress KS, Soria JC. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J Clin Oncol. 2017 Dec 20;35(36):4027-4034. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.73.9250 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28968167/ PubMed] |
− | ##'''Update:''' Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Shi X, Rukazenkov Y, Haddad V, Thress KS, Soria JC. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J Clin Oncol. 2017 Dec 20;35(36):4027-4034. Epub 2017 Oct 2. [https://doi.org/10.1200/JCO.2017.73.9250 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28968167 PubMed] | + | #'''CheckMate 722:''' Mok T, Nakagawa K, Park K, Ohe Y, Girard N, Kim HR, Wu YL, Gainor J, Lee SH, Chiu CH, Kim SW, Yang CT, Wu CL, Wu L, Lin MC, Samol J, Ichikado K, Wang M, Zhang X, Sylvester J, Li S, Forslund A, Yang JC. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722. J Clin Oncol. 2024 Apr 10;42(11):1252-1264. Epub 2024 Jan 22. [https://doi.org/10.1200/jco.23.01017 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095864/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38252907/ PubMed] [https://clinicaltrials.gov/study/NCT02864251 NCT02864251] |
+ | #'''ATTLAS:''' Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. [https://doi.org/10.1200/jco.23.01891 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11095857/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/37861993/ PubMed] [https://clinicaltrials.gov/study/NCT03991403 NCT03991403] | ||
+ | #'''HERTHENA-Lung02:''' [https://clinicaltrials.gov/study/NCT05338970 NCT05338970] | ||
=Advanced or metastatic disease, EGFR p.T790M mutation= | =Advanced or metastatic disease, EGFR p.T790M mutation= | ||
==Carboplatin & Pemetrexed {{#subobject:60fd1d|Regimen=1}}== | ==Carboplatin & Pemetrexed {{#subobject:60fd1d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:95c37d|Variant=1}}=== | ===Regimen {{#subobject:95c37d|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 1,403: | Line 2,293: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
− | |2014-2015 | + | |2014-08 to 2015-09 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Osimertinib_monotherapy_3|Osimertinib]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *Progression after first-line EGFR TKI therapy | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR p.T790M mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second''' | *[[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''' | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*(Ardizzoni et al. 2012 contained more details): | *(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 | + | *[[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 |
− | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of | + | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, 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 | + | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy |
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Optional [[#Pemetrexed_monotherapy_2|pemetrexed]] maintenance | |
− | *Optional [[#Pemetrexed_monotherapy_2|pemetrexed | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https://doi.org/10.1056/NEJMoa1612674 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27959700/ PubMed] [https://clinicaltrials.gov/study/NCT02151981 NCT02151981] | |
− | #'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https:// | + | ##'''PRO analysis:''' Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. [https://doi.org/10.1200/jco.2017.77.2293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29733770/ PubMed] |
− | ##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262 PubMed] | + | ##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262/ PubMed] |
− | ##'''Update:''' Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 | + | ##'''Update:''' Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. [https://doi.org/10.1016/j.annonc.2020.08.2100 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32861806/ PubMed] |
==Cisplatin & Pemetrexed {{#subobject:26b03e|Regimen=1}}== | ==Cisplatin & Pemetrexed {{#subobject:26b03e|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:7dcf71|Variant=1}}=== | ===Regimen {{#subobject:7dcf71|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
Line 1,447: | Line 2,337: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
− | |2014-2015 | + | |2014-08 to 2015-09 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Osimertinib_monotherapy_3|Osimertinib]] |
| style="background-color:#d73027" |Inferior PFS | | style="background-color:#d73027" |Inferior PFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *Progression after first-line EGFR TKI therapy | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR p.T790M mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*(as described in Scagliotti et al. 2008): | *(as described in Scagliotti et al. 2008): | ||
− | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to | + | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to pemetrexed |
*[[Folic acid (Folate)]] 1 mg PO once per day | *[[Folic acid (Folate)]] 1 mg PO once per day | ||
− | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for | + | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for pemetrexed." |
− | |||
'''21-day cycle for 4 to 6 cycles''' | '''21-day cycle for 4 to 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *AURA3, patients without disease progression after 4 cycles: Optional [[#Pemetrexed_monotherapy_2|pemetrexed]] maintenance | |
− | * | + | </div></div> |
===References=== | ===References=== | ||
− | + | #'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https://doi.org/10.1056/NEJMoa1612674 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27959700/ PubMed] [https://clinicaltrials.gov/study/NCT02151981 NCT02151981] | |
− | #'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https:// | + | ##'''PRO analysis:''' Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. [https://doi.org/10.1200/jco.2017.77.2293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29733770/ PubMed] |
− | ##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262 PubMed] | + | ##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262/ PubMed] |
− | ##'''Update:''' Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 | + | ##'''Update:''' Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. [https://doi.org/10.1016/j.annonc.2020.08.2100 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32861806/ PubMed] |
==Docetaxel & Bevacizumab {{#subobject:7bac63|Regimen=1}}== | ==Docetaxel & Bevacizumab {{#subobject:7bac63|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:0ac226|Variant=1}}=== | ===Regimen {{#subobject:0ac226|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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.lungcan.2018.04.012 Nie et al. 2018 (QingdaoCH20161101)] |
− | |2015-2016 | + | |2015-04 to 2016-05 |
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
|[[#Osimertinib_monotherapy_3|Osimertinib]] | |[[#Osimertinib_monotherapy_3|Osimertinib]] | ||
Line 1,497: | Line 2,388: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm. | + | ''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:#fdcdac"> | ||
+ | ====Biomarker eligibility criteria==== | ||
+ | *EGFR p.T790M mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1 | *[[Bevacizumab (Avastin)]] 7.5 mg/kg IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #'''QingdaoCH20161101:''' Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.012 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29858027/ PubMed] [https://clinicaltrials.gov/study/NCT02959749 NCT02959749] | |
− | #'''QingdaoCH20161101:''' Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. [https:// | ||
− | |||
==Osimertinib monotherapy {{#subobject:PYR2|Regimen=1}}== | ==Osimertinib monotherapy {{#subobject:PYR2|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:PYV2|Variant=1}}=== | ===Regimen {{#subobject:PYV2|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 1,523: | Line 2,411: | ||
{| 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 | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1411817 Jänne et al. 2015 (AURA)] |
− | |2013 | + | |2013 to not reported |
− | | style="background-color:#91cf61" |Phase 1 | + | | style="background-color:#91cf61" |Phase 1/2 (RT) |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(16)30508-3 Goss et al. 2016 (AURA2)] |
|2014 | |2014 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 (RT) |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ Mok et al. 2016 (AURA3)] | ||
− | |2014-2015 | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-62-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2014-08 to 2015-09 | ||
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc) | ||
− | | | + | |1a. [[#Carboplatin_.26_Pemetrexed_3|Carboplatin & Pemetrexed]]<br>1b. [[#Cisplatin_.26_Pemetrexed_4|Cisplatin & Pemetrexed]] |
− | | style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.1 vs 4.4 mo<br>(HR 0.30, 95% CI 0.23-0.41) | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.1 vs 4.4 mo<br>(HR 0.30, 95% CI 0.23-0.41)<br><br>Did not meet secondary endpoint of OS<sup>1</sup><br>Median OS: 26.8 vs 22.5 mo<br>(HR 0.87, 95% CI 0.67-1.12) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.lungcan.2018.04.012 Nie et al. 2018 (QingdaoCH20161101)] |
− | |2015-2016 | + | |2015-04 to 2016-05 |
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
|[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] | |[[#Docetaxel_.26_Bevacizumab|Docetaxel & Bevacizumab]] | ||
− | | style="background-color:#1a9850" |Superior PFS | + | | style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.2 vs 3 mo<br>(HR 0.23, 95% CI 0.12-0.38)<br><br>Did not meet secondary endpoint of OS<br>(HR 0.79, 95% CI 0.38-1.60) |
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for OS endpoint in AURA3 is based on the 2020 update.'' |
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
+ | ====Prior treatment criteria==== | ||
+ | *AURA3: Progression after first-line EGFR TKI therapy | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*AURA3: EGFR p.T790M mutation | *AURA3: EGFR p.T790M mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Osimertinib (Tagrisso)]] 80 mg PO once per day | *[[Osimertinib (Tagrisso)]] 80 mg PO once per day | ||
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'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''AURA:''' Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. [https://doi.org/10.1056/NEJMoa1411817 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25923549/ PubMed] [https://clinicaltrials.gov/study/NCT01802632 NCT01802632] | |
− | #''' | + | ##'''Update:''' Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, Blackhall F, Haggstrom D, Yoh K, Novello S, Gold K, Hirashima T, Lin CC, Mann H, Cantarini M, Ghiorghiu S, Jänne PA. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol. 2017 Apr 20;35(12):1288-1296. Epub 2017 Feb 21. [https://doi.org/10.1200/jco.2016.70.3223 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28221867/ PubMed] |
− | ##''' | + | ##'''Pooled update:''' Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. [https://doi.org/10.1093/annonc/mdx820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29293889/ PubMed] [https://clinicaltrials.gov/study/NCT01802632 NCT01802632] |
− | ##'''Pooled update:''' | + | ##'''Pooled update:''' Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Jänne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. Epub 2018 Dec 4. [https://doi.org/10.1002/cncr.31891 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30512189/ PubMed] |
− | ##'''Pooled | + | #'''AURA2:''' Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. Epub 2016 Oct 14. [https://doi.org/10.1016/S1470-2045(16)30508-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27751847/ PubMed] [https://clinicaltrials.gov/study/NCT02094261 NCT02094261] |
− | + | ##'''Pooled subgroup analysis:''' Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. [https://doi.org/10.1093/annonc/mdx820 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29293889/ PubMed] | |
− | #''' | + | ##'''Pooled update:''' Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Jänne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. Epub 2018 Dec 4. [https://doi.org/10.1002/cncr.31891 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30512189/ PubMed] |
− | ##'''Pooled update:''' | + | #'''AURA3:''' Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. [https://doi.org/10.1056/NEJMoa1612674 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762027/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27959700/ PubMed] [https://clinicaltrials.gov/study/NCT02151981 NCT02151981] |
− | + | ##'''PRO analysis:''' Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. [https://doi.org/10.1200/jco.2017.77.2293 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29733770/ PubMed] | |
− | + | ##'''Subgroup analysis:''' Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. [https://doi.org/10.1200/JCO.2018.77.9363 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30059262/ PubMed] | |
− | + | ##'''Update:''' Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. [https://doi.org/10.1016/j.annonc.2020.08.2100 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32861806/ PubMed] | |
− | + | #'''QingdaoCH20161101:''' Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.012 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/29858027/ PubMed] [https://clinicaltrials.gov/study/NCT02959749 NCT02959749] | |
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[[Category:Non-small cell lung cancer regimens]] | [[Category:Non-small cell lung cancer regimens]] | ||
[[Category:Biomarker-specific pages]] | [[Category:Biomarker-specific pages]] | ||
[[Category:Non-small cell lung cancers]] | [[Category:Non-small cell lung cancers]] |
Latest revision as of 23:45, 24 July 2024
Page editor | Section editor | ||
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Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX, USA |
Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA |
Note: these are regimens tested in biomarker-specific populations, please see the main NSCLC page for other regimens.
There are several related dedicated pages:
- Histology-specific:
- Site-specific:
46 regimens on this page
63 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2023: Jaiyesimi et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2022.3 PubMed
ESMO
- 2023: Hendriks et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2022: Passaro et al. ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer PubMed
IASLC
- 2016: Tan et al. The International Association for the Study of Lung Cancer consensus statement on optimizing management of EGFR mutation–positive non–small cell lung cancer: Status in 2016 PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Non-Small Cell Lung Cancer.
Neoadjuvant therapy
Carboplatin & Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (NeoADAURA) | 2020-ongoing | Phase 3 (C) | 1a. Pem-Carbo & Osimertinib 1b. Pem-Cis & Osimertinib 2. Osimertinib |
TBD if different primary endpoint of major pathological response |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- NeoADAURA: NCT04351555
Cisplatin & Pemetrexed
Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (NeoADAURA) | 2020-ongoing | Phase 3 (C) | 1a. Pem-Carbo & Osimertinib 1b. Pem-Cis & Osimertinib 2. Osimertinib |
TBD if different primary endpoint of major pathological response |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- NeoADAURA: NCT04351555
Adjuvant therapy
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
Regimen variant #1, 75/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhong et al. 2017 (ADJUVANT/CTONG1104) | 2011-2014 | Phase 3 (C) | Gefinitib | Inferior DFS |
Biomarker eligibility criteria
- EGFR exon 19 deletion or EGFR p.L858R
Preceding treatment
- Complete surgical resection, within 6 to 12 weeks
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Regimen variant #2, 80/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tada et al. 2021 (IMPACTNSCLC) | 2011-2015 | Phase 3 (C) | Gefinitib | Did not meet primary endpoint of DFS |
Note: this trial should not be confused by those with the same name in prostate cancer and colon cancer.
Biomarker eligibility criteria
- EGFR exon 19 deletion or EGFR p.L858R
Preceding treatment
- Complete surgical resection, within 3 to 8 weeks
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
References
- ADJUVANT/CTONG1104: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01405079
- Update: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. link to original article link to PMC article PubMed
- IMPACTNSCLC: Tada H, Mitsudomi T, Misumi T, Sugio K, Tsuboi M, Okamoto I, Iwamoto Y, Sakakura N, Sugawara S, Atagi S, Takahashi T, Hayashi H, Okada M, Inokawa H, Yoshioka H, Takahashi K, Higashiyama M, Yoshino I, Nakagawa K; West Japan Oncology Group. Randomized Phase III Study of Gefitinib Versus Cisplatin Plus Vinorelbine for Patients With Resected Stage II-IIIA Non-Small-Cell Lung Cancer With EGFR Mutation (IMPACT). J Clin Oncol. 2022 Jan 20;40(3):231-241. Epub 2021 Nov 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000006252
Gefitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhong et al. 2017 (ADJUVANT/CTONG1104) | 2011-2014 | Phase 3 (E-switch-ooc) | Cisplatin & Vinorelbine | Superior DFS (primary endpoint) Median DFS: 28.7 vs 18 mo (HR 0.60, 95% CI 0.42-0.87) |
Biomarker eligibility criteria
- Biomarker: EGFR exon 19 deletion and exon 21 L858R activating mutations
Preceding treatment
References
- ADJUVANT/CTONG1104: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. Epub 2017 Nov 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01405079
- Update: Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Wei YC, Liu YY, Chen C, Cheng Y, Yin R, Yang F, Ren SX, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yang JJ, Yan HH, Yang XN, Liu SY, Zhou Q, Wu YL. Gefitinib Versus Vinorelbine Plus Cisplatin as Adjuvant Treatment for Stage II-IIIA (N1-N2) EGFR-Mutant NSCLC: Final Overall Survival Analysis of CTONG1104 Phase III Trial. J Clin Oncol. 2021 Mar 1;39(7):713-722. Epub 2020 Dec 17. link to original article link to PMC article PubMed
Icotinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
He et al. 2021 (EVIDENCE) | 2015-06-08 to 2019-08-02 | Phase 3 (E-switch-ooc) | 1a. Cisplatin & Pemetrexed 1b. Cisplatin & Vinorelbine |
Superior DFS (primary endpoint) Median DFS: 47 vs 22.1 mo (HR 0.36, 95% CI 0.24-0.55) |
Note: this drug is only approved in China; eligible patients had stage IIIB/IV lung adenocarcinoma.
Biomarker eligibility criteria
- EGFR exon 19 or 21 mutations
Preceding treatment
- Complete resection, within 8 weeks
References
- EVIDENCE: He J, Su C, Liang W, Xu S, Wu L, Fu X, Zhang X, Ge D, Chen Q, Mao W, Xu L, Chen C, Hu B, Shao G, Hu J, Zhao J, Liu X, Liu Z, Wang Z, Xiao Z, Gong T, Lin W, Li X, Ye F, Liu Y, Ma H, Huang Y, Zhou J, Wang Z, Fu J, Ding L, Mao L, Zhou C. Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial. Lancet Respir Med. 2021 Sep;9(9):1021-1029. Epub 2021 Jul 21. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT02448797
Osimertinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2020 (ADAURA) | 2015-11 to 2019-02 | Phase 3 (E-RT-esc) | Placebo | Superior DFS1 (primary endpoint) DFS48: 73% vs 38% (HR 0.27, 95% CI 0.21-0.34) Superior OS2 (secondary endpoint) OS60: 85% vs 73% (HR 0.49, 95.03% CI 0.33-0.73) |
1Reported efficacy is based on the January 2023 update.
2Reported efficacy is based on the June 2023 update.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation, alone or in combination with other EGFR mutations
Preceding treatment
References
- ADAURA: Wu YL, Tsuboi M, He J, John T, Grohe C, Majem M, Goldman JW, Laktionov K, Kim SW, Kato T, Vu HV, Lu S, Lee KY, Akewanlop C, Yu CJ, de Marinis F, Bonanno L, Domine M, Shepherd FA, Zeng L, Hodge R, Atasoy A, Rukazenkov Y, Herbst RS; ADAURA Investigators. Osimertinib in Resected EGFR-Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020 Oct 29;383(18):1711-1723. Epub 2020 Sep 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02511106
- Update: Herbst RS, Wu YL, John T, Grohe C, Majem M, Wang J, Kato T, Goldman JW, Laktionov K, Kim SW, Yu CJ, Vu HV, Lu S, Lee KY, Mukhametshina G, Akewanlop C, de Marinis F, Bonanno L, Domine M, Shepherd FA, Urban D, Huang X, Bolanos A, Stachowiak M, Tsuboi M. Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non-Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial. J Clin Oncol. 2023 Apr 1;41(10):1830-1840. Epub 2023 Jan 31. link to original article link to PMC article PubMed
- Update: Tsuboi M, Herbst RS, John T, Kato T, Majem M, Grohé C, Wang J, Goldman JW, Lu S, Su WC, de Marinis F, Shepherd FA, Lee KH, Le NT, Dechaphunkul A, Kowalski D, Poole L, Bolanos A, Rukazenkov Y, Wu YL; ADAURA Investigators. Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC. N Engl J Med. 2023 Jul 13;389(2):137-147. Epub 2023 Jun 4. link to original article PubMed
Advanced or metastatic disease, platinum-exposed
Amivantamab monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Park et al. 2021 (CHRYSALIS) | 2016-2020 | Phase 1 (RT) |
Note: Dosing details are from the FDA announcement.
Biomarker eligibility criteria
- EGFR exon 20 insertion
Targeted therapy
- Amivantamab (Rybrevant) by the following weight-based criteria:
- Less than 80 kg: 1050 mg IV once on day 1
- 80 kg or more: 1400 mg IV once on day 1
7-day cycle for 4 cycles, then 14-day cycles
References
- CHRYSALIS: Park K, Haura EB, Leighl NB, Mitchell P, Shu CA, Girard N, Viteri S, Han JY, Kim SW, Lee CK, Sabari JK, Spira AI, Yang TY, Kim DW, Lee KH, Sanborn RE, Trigo J, Goto K, Lee JS, Yang JC, Govindan R, Bauml JM, Garrido P, Krebs MG, Reckamp KL, Xie J, Curtin JC, Haddish-Berhane N, Roshak A, Millington D, Lorenzini P, Thayu M, Knoblauch RE, Cho BC. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study. J Clin Oncol. 2021 Oct 20;39(30):3391-3402. Epub 2021 Aug 2. link to original article link to PMC article PubMed NCT02609776
Mobocertinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Riely et al. 2021 (AP32788-15-101) | 2016-2020 | Phase 1/2 (RT) |
Note: this was the dose used in the phase 2 portion.
Biomarker eligibility criteria
- EGFR exon 20 insertion mutations
References
- AP32788-15-101: Riely GJ, Neal JW, Camidge DR, Spira AI, Piotrowska Z, Costa DB, Tsao AS, Patel JD, Gadgeel SM, Bazhenova L, Zhu VW, West HL, Mekhail T, Gentzler RD, Nguyen D, Vincent S, Zhang S, Lin J, Bunn V, Jin S, Li S, Jänne PA. Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations from a Phase I/II Trial. Cancer Discov. 2021 Jul;11(7):1688-1699. Epub 2021 Feb 25. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02716116
- Update: Zhou C, Ramalingam SS, Kim TM, Kim SW, Yang JC, Riely GJ, Mekhail T, Nguyen D, Garcia Campelo MR, Felip E, Vincent S, Jin S, Griffin C, Bunn V, Lin J, Lin HM, Mehta M, Jänne PA. Treatment Outcomes and Safety of Mobocertinib in Platinum-Pretreated Patients With EGFR Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer: A Phase 1/2 Open-label Nonrandomized Clinical Trial. JAMA Oncol. 2021 Dec 1;7(12):e214761. Epub 2021 Dec 16. Erratum in: JAMA Oncol. 2022 Feb 24. link to original article link to PMC article PubMed
Advanced or metastatic disease, EGFR inhibitor-naive
Afatinib monotherapy
Regimen variant #1, 30 mg/day
FDA-recommended dose |
Note: This is the FDA-recommended dose for patients with "severe renal impairment".
Regimen variant #2, 40 mg/day
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yang et al. 2012 (LUX-Lung 2) | 2007-2009 | Phase 2 (RT) | ORR: 61% | |
Sequist et al. 2013 (LUX-Lung 3) | 2009-2011 | Phase 3 (E-RT-switch-ooc) | Cisplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 11.1 vs 6.9 mo (HR 0.58, 95% CI 0.43-0.78) |
Wu et al. 2014 (LUX-Lung 6) | 2010-04-27 to 2011-11-16 | Phase 3 (E-RT-switch-ooc) | Cisplatin & Gemcitabine | Superior PFS (primary endpoint) Median PFS: 11 vs 5.6 mo (HR 0.28, 95% CI 0.20-0.39) |
Park et al. 2016 (LUX-Lung 7) | 2011-2013 | Randomized Phase 2 (E-switch-ic) | Gefitinib | Superior PFS (co-primary endpoint) Median PFS: 11 vs 10.9 mo (HR 0.73, 95% CI 0.57-0.95) |
Biomarker eligibility criteria
- LUX-Lung 2: activating EGFR mutations within exons 18–21
- LUX-Lung 3 & LUX-Lung 6: Activating EGFR mutation with exon 19 deletions, L858R, insertions in exon 20, L861Q, G719S, G719A, G719C, T790M, or S768I
- LUX-Lung 7: Activating EGFR mutation with exon 19 deletion and/or L858R
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day, taken 1 hour before eating food (LUX-Lung 2: "no food intake immediately before or after afatinib")
Continued indefinitely
Dose and schedule modifications
- In LUX-Lung 3 & LUX-Lung 7, patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event.
References
- LUX-Lung 2: Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00525148
- Pooled subgroup analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- LUX-Lung 3: Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00949650
- HRQoL analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. link to original article PubMed
- Pooled subgroup analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. link to original article PubMed
- LUX-Lung 6: Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. Epub 2014 Jan 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01121393
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. link to original article PubMed
- Pooled subgroup analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. link to original article PubMed
- LUX-Lung 7: Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01466660
Apatinib & Gefitinib
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhao et al. 2021 (CTONG1706) | 2017-08 to 2018-12 | Phase 3 (E-esc) | Gefitinib | Superior PFS (primary endpoint) Median PFS: 13.7 vs 10.2 mo (HR 0.71, 95% CI 0.54-0.95) |
Biomarker eligibility criteria
- EGFR exon 19 deletion or exon 21 L858R mutation
Targeted therapy
- Apatinib (Aitan) 500 mg PO once per day
- Gefitinib (Iressa) 250 mg PO once per day
Continued indefinitely
References
- CTONG1706: Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q, Wu G, Jiang O, Du X, Liu J, Gu W, Hou Z, Wang Q, Zheng R, Zhou X, Zhang L. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. Epub 2021 May 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02824458
Aumolertinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lu et al. 2022 (AENEAS) | 2018-11-30 to 2019-09-06 | Phase 3 (E-switch-ic) | Gefitinib | Superior PFS Median PFS: 19.3 vs 9.9 mo (HR 0.46, 95% CI 0.36-0.60) |
Biomarker eligibility criteria
- EGFR exon 19 deletion or L858R
References
- AENEAS: Lu S, Dong X, Jian H, Chen J, Chen G, Sun Y, Ji Y, Wang Z, Shi J, Lu J, Chen S, Lv D, Zhang G, Liu C, Li J, Yu X, Lin Z, Yu Z, Wang Z, Cui J, Xu X, Fang J, Feng J, Xu Z, Ma R, Hu J, Yang N, Zhou X, Wu X, Hu C, Zhang Z, Lu Y, Hu Y, Jiang L, Wang Q, Guo R, Zhou J, Li B, Hu C, Tong W, Zhang H, Ma L, Chen Y, Jie Z, Yao Y, Zhang L, Jie W, Li W, Xiong J, Ye X, Duan J, Yang H, Sun M, Sun C, Wei H, Li C, Ali SM, Miller VA, Wu Q. AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations. J Clin Oncol. 2022 Sep 20;40(27):3162-3171. Epub 2022 May 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03849768
Carboplatin & Docetaxel
DCb: Docetaxel & Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker eligibility criteria
- Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 4 cycles
References
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00446225
Carboplatin & Gemcitabine (GCb)
GC: Gemcitabine & Carboplatin
GCa: Gemcitabine & Carboplatin
GCb: Gemcitabine & Carboplatin
Regimen variant #1, 5/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Zhou et al. 2011 (CTONG-0802) | 2008-08-24 to 2009-07-17 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker eligibility criteria
- Biomarker: EGFR activating mutation with exon 19 deletion or p.L858R mutation in exon 21
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 4 cycles
Regimen variant #2, 5/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-04-29 to 2010-09-09 | Phase 3 (C) | 1a. Carboplatin & Gemcitabine/Erlotinib 1b. GC/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
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
References
- CTONG-0802: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00874419
- Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00446225
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00883779
Carboplatin & Gemcitabine/Erlotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-04-29 to 2010-09-09 | Phase 3 (E-esc) | 1a. Carboplatin & Gemcitabine 1b. Cisplatin & Gemcitabine |
Superior PFS (primary endpoint) Median PFS: 7.6 vs 6 mo (HR 0.57, 95% CI 0.47-0.69) Seems to have superior OS (secondary endpoint) Median OS: 18.3 vs 15.2 mo (HR 0.79, 95% CI 0.64-0.99) |
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
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 15 to 28
28-day cycle for 6 cycles
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00883779
Carboplatin & Paclitaxel (CP)
CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin
TC: Taxol (Paclitaxel) & Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Maemondo et al. 2010 (NEJ002) | 2006-2009 | Phase 3 (C) | Gefitinib | Inferior PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for at least 3 cycles
References
- NEJ002: Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000376
- HRQoL analysis: Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. link to original article link to PMC article PubMed
- Update: Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. link to original article PubMed
Carboplatin & Pemetrexed
Regimen variant #1, 4 cycles of carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhou et al. 2023 (PAPILLON) | 2020-12 to 2022-11 | Phase 3 (C) | Carboplatin, Pemetrexed, Amivantamab | Inferior PFS |
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Biomarker eligibility criteria
- EGFR exon 20 insertions
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, 6 cycles of carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Patil et al. 2017 | 2012-2016 | Phase 3 (C) | Gefitinib | Inferior PFS |
Note: To our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Biomarker eligibility criteria
- Activating EGFR mutation in exons 18, 19, or 21
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV over 30 minutes once on day 1, given second
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
21-day cycles
References
- Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- PAPILLON: Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourão Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med. 2023 Nov 30;389(22):2039-2051. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04538664
Carboplatin, Pemetrexed, Amivantamab
Regimen variant #1, lower-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhou et al. 2023 (PAPILLON) | 2020-12 to 2022-11 | Phase 3 (E-RT-esc) | Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 11.4 vs 6.7 mo (HR 0.40, 95% CI 0.30-0.53) |
Note: This amivantamab dosage was for patients weighing less than 80 kg.
Biomarker eligibility criteria
- EGFR exon 20 insertions
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15
- Cycle 2: 1400 mg IV once on day 1
- Cycle 3 onwards: 1750 mg IV once on day 1
21-day cycles
Regimen variant #2, higher-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhou et al. 2023 (PAPILLON) | 2020-12 to 2022-11 | Phase 3 (E-RT-esc) | Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 11.4 vs 6.7 mo (HR 0.40, 95% CI 0.30-0.53) |
Note: This amivantamab dosage was for patients weighing 80 kg or more.
Biomarker eligibility criteria
- EGFR exon 20 insertions
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15
- Cycle 2: 1750 mg IV once on day 1
- Cycle 3 onwards: 2100 mg IV once on day 1
21-day cycles
References
- PAPILLON: Zhou C, Tang KJ, Cho BC, Liu B, Paz-Ares L, Cheng S, Kitazono S, Thiagarajan M, Goldman JW, Sabari JK, Sanborn RE, Mansfield AS, Hung JY, Boyer M, Popat S, Mourão Dias J, Felip E, Majem M, Gumus M, Kim SW, Ono A, Xie J, Bhattacharya A, Agrawal T, Shreeve SM, Knoblauch RE, Park K, Girard N; PAPILLON Investigators. Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions. N Engl J Med. 2023 Nov 30;389(22):2039-2051. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04538664
Carboplatin, Osimertinib, Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Planchard et al. 2023 (FLAURA2) | 2020-06-01 to 2021-12-22 | Phase 3 (E-RT-esc) | Osimertinib | Superior PFS (primary endpoint) PFS24: 57% vs 41% (HR 0.62, 95% CI 0.49-0.79) |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day on days 1 to 21
21-day cycles
References
- FLAURA2: Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04035486
- Subgroup analysis: Jänne PA, Planchard D, Kobayashi K, Cheng Y, Lee CK, Valdiviezo N, Laktionov K, Yang TY, Yu Y, Kato T, Jiang L, Chewaskulyong B, Lucien Geater S, Maurel JM, Rojas C, Takahashi T, Havel L, Shepherd FA, Tanaka K, Ghiorghiu D, Amin NP, Armenteros-Monterroso E, Huang X, Chaudhry AA, Yang JC. CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2024 Mar 1;42(7):808-820. Epub 2023 Dec 2. link to original article link to PMC article PubMed
Cisplatin & Docetaxel (DC)
DC: Docetaxel & Cisplatin
DP: Docetaxel & Platinol (Cisplatin)
Doc-Cis: Docetaxel & Cisplatin
Regimen variant #1, 75/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for up to 4 cycles
Regimen variant #2, 80/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitsudomi et al. 2009 (WJTOG3405) | 2006-2009 | Phase 3 (C) | Gefitinib | Inferior PFS |
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 90 minutes once on day 1, given second
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycle for 3 to 6 cycles
References
- WJTOG3405: Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000539
- Update: Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. link to original article PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00446225
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)
Regimen variant #1, 75/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2014 (LUX-Lung 6) | 2010-04-27 to 2011-11-16 | Phase 3 (C) | Afatinib | Inferior PFS |
Biomarker eligibility criteria
- EGFR mutation-positive
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #2, 75/1250 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (C) | Erlotinib | Inferior PFS |
Wu et al. 2015 (ENSURE) | 2011-03 to 2012-06 | Phase 3 (C) | Erlotinib | Inferior PFS |
Biomarker eligibility criteria
- EURTAC: EGFR exon 19 deletion or p.L858R mutation in exon 21
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 2 hours once per day on days 1 & 8
21-day cycle for up to 4 cycles
Regimen variant #3, 75/1250 q4wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-04-29 to 2010-09-09 | Phase 3 (C) | 1a. Carboplatin & Gemcitabine/Erlotinib 1b. GC/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
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
28-day cycle for 6 cycles
References
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00446225
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00883779
- LUX-Lung 6: Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. Epub 2014 Jan 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01121393
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. link to original article PubMed
- Pooled subgroup analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. link to original article PubMed
- ENSURE: Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01342965
Cisplatin & Gemcitabine/Erlotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wu et al. 2013 (FASTACT-2) | 2009-04-29 to 2010-09-09 | Phase 3 (E-esc) | 1a. Carboplatin & Gemcitabine 1b. Cisplatin & Gemcitabine |
Superior PFS (primary endpoint) Median PFS: 7.6 vs 6 mo (HR 0.57, 95% CI 0.47-0.69) Seems to have superior OS (secondary endpoint) Median OS: 18.3 vs 15.2 mo (HR 0.79, 95% CI 0.64-0.99) |
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
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 15 to 28
28-day cycle for 6 cycles
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00883779
Cisplatin & Pemetrexed
Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed
Regimen variant #1, limited duration
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sequist et al. 2013 (LUX-Lung 3) | 2009-2011 | Phase 3 (C) | Afatinib | Inferior PFS |
Biomarker eligibility criteria
- Activating mutations in EGFR
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given second
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- (as described in JMDB):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to pemetrexed
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for pemetrexed."
21-day cycle for 4 to 6 cycles
Regimen variant #2, with maintenance
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shi et al. 2017 (CONVINCE) | 2013-01 to 2014-08 | Phase 3 (C) | Icotinib | Inferior PFS |
Biomarker eligibility criteria
- EGFR exon 19/21 mutations
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive therapy
- (as described in JMDB):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to pemetrexed
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for pemetrexed."
21-day cycles
References
- LUX-Lung 3: Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00949650
- HRQoL analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pooled update: Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. Epub 2015 Jan 12. link to original article PubMed
- Pooled subgroup analysis: Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. Epub 2015 Jun 4. link to original article PubMed
- Subgroup analysis: Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. Epub 2016 Jan 25. link to original article PubMed
- CONVINCE: Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01719536
Cisplatin, Osimertinib, Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Planchard et al. 2023 (FLAURA2) | 2020-06-01 to 2021-12-22 | Phase 3 (E-RT-esc) | Osimertinib | Superior PFS (primary endpoint) PFS24: 57% vs 41% (HR 0.62, 95% CI 0.49-0.79) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Osimertinib (Tagrisso) 80 mg PO once per day on days 1 to 21
21-day cycles
References
- FLAURA2: Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04035486
Dacomitinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ramalingam et al. 2012 (A7471028) | 2008-2009 | Randomized Phase 2 (E-switch-ic) | Erlotinib | Seems to have superior PFS (primary endpoint) Median PFS: 2.9 vs 1.9 mo (HR 0.66, 95% CI 0.47-0.91) |
Ramalingam et al. 2014 (ARCHER 1009) | 2011-2013 | Phase 3 (E-switch-ic) | Erlotinib | Did not meet primary endpoint of PFS Median PFS: 2.6 vs 2.6 mo (HR 0.94, 95% CI 0.80-1.10) |
Wu et al. 2017 (ARCHER 1050) | 2013-2015 | Phase 3 (E-RT-switch-ic) | Gefitinib | Superior PFS (primary endpoint) Median PFS: 14.7 vs 9.2 mo (HR 0.59, 95% CI 0.47-0.74) Seems to have superior OS1 (secondary endpoint) Median OS: 34.1 vs 27 mo (HR 0.75, 95% CI 0.59-0.95) |
1Reported efficacy for OS in ARCHER 1050 is based on the 2021 update.
Biomarker eligibility criteria
- A7471028 & ARCHER 1009: None
- ARCHER 1050: Activating mutations in EGFR
References
- A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00769067
- ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01360554
- ARCHER 1050: Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01774721
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. link to original article PubMed
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. link to original article link to PMC article PubMed
Erlotinib monotherapy
Regimen variant #1, 150 mg/d
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rossell et al. 2012 (EURTAC) | 2007-2011 | Phase 3 (E-RT-switch-ooc) | 1a. Carboplatin & Docetaxel 1b. Carboplatin & Gemcitabine 1c. Cisplatin & Docetaxel 1d. Cisplatin & Gemcitabine |
Superior PFS (primary endpoint) Median PFS: 9.7 vs 5.2 mo (HR 0.37, 95% CI 0.25-0.54) |
Zhou et al. 2011 (CTONG-0802) | 2008-08-24 to 2009-07-17 | Phase 3 (E-switch-ooc) | Carboplatin & Gemcitabine | Superior PFS (primary endpoint) Median PFS: 13.1 vs 4.6 mo (HR 0.16, 95% CI 0.10-0.26) |
Ramalingam et al. 2012 (A7471028) | 2008-2009 | Randomized Phase 2 (C) | Dacomitinib | Seems to have inferior PFS |
Yang et al. 2017 (CTONG 0901) | 2009-2014 | Phase 3 (E-switch-ic) | Gefitinib | Might have superior PFS (primary endpoint) Median PFS: 13 vs 10.4 mo (HR 0.81, 95% CI 0.62-1.05) |
Seto et al. 2014 (JO25567) | 2011-2012 | Randomized Phase 2 (C) | Erlotinib & Bevacizumab | Inferior PFS |
Wu et al. 2015 (ENSURE) | 2011-03 to 2012-06 | Phase 3 (E-switch-ooc) | Cisplatin & Gemcitabine | Superior PFS (primary endpoint) Median PFS: 11.0 vs 5.5 mo (HR 0.34, 95% CI 0.22-0.51) Did not meet secondary endpoint of OS Median OS: 26.3 vs 25.5 mo (HR 0.91, 95% CI 0.63-1.31) |
Ramalingam et al. 2014 (ARCHER 1009) | 2011-2013 | Phase 3 (C) | Dacomitinib | Did not meet primary endpoint of PFS |
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (C) | Osimertinib | Seems to have inferior OS1 |
Saito et al. 2019 (NEJ026) | 2015-06-03 to 2016-08-31 | Phase 3 (C) | Erlotinib & Bevacizumab | Seems to have inferior PFS |
Nakagawa et al. 2019 (RELAY) | 2016-01-28 to 2018-02-01 | Phase 3 (C) | Erlotinib & Ramucirumab | Inferior PFS |
Kelly et al. 2019 (SOLARNSCLC) | 2016-02-11 to 2017-12-21 | Phase 3 (C) | Naquotinib | Did not meet primary endpoint of PFS Median PFS: 9.6 vs 9.3 mo (HR 0.62) |
Zhou et al. 2021 (ARTEMIS-CTONG1509) | 2016-05 to 2017-07 | Phase 3 (C) | Erlotinib & Bevacizumab | Inferior PFS |
Piccirillo et al. 2022 (BEVERLY) | 2016-2019 | Phase 3 (C) | Erlotinib & Bevacizumab | Inferior PFS |
1Reported efficacy for FLAURA is based on the 2019 update.
Note: these are all trials restricted to patients with EGFR-mutated lung cancer. Some trials of erlotinib in unselected populations nevertheless had high rates of EGFR-mutated lung cancers, due to the nature of the populations studied. See the main NSCLC page for these trials. SOLAR should not be confused with the trial by the same name in gastric cancer.
Regimen variant #2, low-dose
Study | Dates of enrollment | Evidence |
---|---|---|
Yeo et al. 2010 | 2004-2010 | Retrospective |
References
- Retrospective: Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. link to PMC article PubMed
- CTONG-0802: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00874419
- Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article PubMed
- EURTAC: Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Muñoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group; Groupe Français de Pneumo-Cancérologie; Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. Epub 2012 Jan 26. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00446225
- A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. Epub 2012 Jul 2. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00769067
- JO25567: Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. link to original article dosing details in manuscript have been reviewed by our editors PubMed JapicCTI-111390
- ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01360554
- ENSURE: Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, Lu S, Cheng Y, Han B, Chen L, Huang C, Qin S, Zhu Y, Pan H, Liang H, Li E, Jiang G, How SH, Fernando MC, Zhang Y, Xia F, Zuo Y. First-line erlotinib versus gemcitabine/cisplatin in patients with advanced EGFR mutation-positive non-small-cell lung cancer: analyses from the phase III, randomized, open-label, ENSURE study. Ann Oncol. 2015 Sep;26(9):1883-9. Epub 2015 Jun 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01342965
- CTONG 0901: Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01024413
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
- NEJ026: Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000017069
- Update: Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Seike M, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. Epub 2021 Aug 26. link to original article PubMed
- SOLAR: Kelly RJ, Shepherd FA, Krivoshik A, Jie F, Horn L. A phase 3, randomized, open-label study of ASP8273 versus erlotinib or gefitinib in patients with advanced stage IIIB/IV non-small cell lung cancer. Ann Oncol. 2019 Jul 1;30(7):1127-1133. Epub 2019 May 9. link to original article link to PMC article PubMed NCT02588261
- RELAY: Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02411448
- PRO analysis: Yoh K, Atagi S, Reck M, Garon EB, Ponce Aix S, Moro-Sibilot D, Winfree KB, Frimodt-Moller B, Zimmermann A, Visseren-Grul C, Nakagawa K; RELAY investigators. Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer. Curr Med Res Opin. 2020 Oct;36(10):1667-1675. Epub 2020 Aug 28. link to original article PubMed
- ARTEMIS-CTONG1509: Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. Epub 2021 Aug 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02759614
- BEVERLY: Piccirillo MC, Bonanno L, Garassino MC, Esposito G, Dazzi C, Cavanna L, Burgio MA, Rosetti F, Rizzato S, Morgillo F, Cinieri S, Veccia A, Papi M, Tonini G, Gebbia V, Ricciardi S, Pozzessere D, Ferro A, Proto C, Costanzo R, D'Arcangelo M, Proietto M, Gargiulo P, Di Liello R, Arenare L, De Marinis F, Crinò L, Ciardiello F, Normanno N, Gallo C, Perrone F, Gridelli C, Morabito A. Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial. J Thorac Oncol. 2022 Sep;17(9):1086-1097. Epub 2022 Jun 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02633189
Erlotinib & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Seto et al. 2014 (JO25567) | 2011-2012 | Randomized Phase 2 (E-esc) | Erlotinib | Superior PFS1 (primary endpoint) Median PFS: 16.4 vs 9.8 mo (HR 0.52, 95% CI 0.35-0.76) Did not meet secondary endpoint of OS1 Median OS: 47.4 vs 47 mo (HR 0.81, 95% CI 0.53-1.23) |
Saito et al. 2019 (NEJ026) | 2015-06-03 to 2016-08-31 | Phase 3 (E-esc) | Erlotinib | Seems to have superior PFS (primary endpoint) Median PFS: 16.9 vs 13.3 mo (HR 0.61, 95% CI 0.42-0.88) Did not meet secondary endpoint of OS2 Median OS: 50.7 vs 46.2 mo (HR 1.01, 95% CI 0.68-1.49) |
Zhou et al. 2021 (ARTEMIS-CTONG1509) | 2016-05 to 2017-07 | Phase 3 (E-esc) | Erlotinib | Superior PFS (primary endpoint) Median PFS: 17.9 vs 11.2 mo (HR 0.55, 95% CI 0.41-0.73) |
Piccirillo et al. 2022 (BEVERLY) | 2016-2019 | Phase 3 (E-esc) | Erlotinib | Superior PFS (primary endpoint) Median PFS: 15.4 vs 9.6 mo (HR 0.66, 95% CI 0.47-0.92) |
1Reported efficacy for JO25567 is based on the 2020 update.
2Reported efficacy for OS for NEJ026 is based on the 2021 update.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 21
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- JO25567: Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. Epub 2014 Aug 27. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. link to original article dosing details in manuscript have been reviewed by our editors PubMed JapicCTI-111390
- Update: Yamamoto N, Seto T, Nishio M, Goto K, Yamamoto N, Okamoto I, Yamanaka T, Tanaka M, Takahashi K, Fukuoka M. Erlotinib plus bevacizumab vs erlotinib monotherapy as first-line treatment for advanced EGFR mutation-positive non-squamous non-small-cell lung cancer: Survival follow-up results of the randomized JO25567 study. Lung Cancer. 2021 Jan;151:20-24. Epub 2020 Nov 20. link to original article PubMed
- NEJ026: Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. Epub 2019 Apr 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000017069
- Update: Kawashima Y, Fukuhara T, Saito H, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Seike M, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Bevacizumab plus erlotinib versus erlotinib alone in Japanese patients with advanced, metastatic, EGFR-mutant non-small-cell lung cancer (NEJ026): overall survival analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Respir Med. 2022 Jan;10(1):72-82. Epub 2021 Aug 26. link to original article PubMed
- ARTEMIS-CTONG1509: Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. Epub 2021 Aug 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02759614
- BEVERLY: Piccirillo MC, Bonanno L, Garassino MC, Esposito G, Dazzi C, Cavanna L, Burgio MA, Rosetti F, Rizzato S, Morgillo F, Cinieri S, Veccia A, Papi M, Tonini G, Gebbia V, Ricciardi S, Pozzessere D, Ferro A, Proto C, Costanzo R, D'Arcangelo M, Proietto M, Gargiulo P, Di Liello R, Arenare L, De Marinis F, Crinò L, Ciardiello F, Normanno N, Gallo C, Perrone F, Gridelli C, Morabito A. Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial. J Thorac Oncol. 2022 Sep;17(9):1086-1097. Epub 2022 Jun 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02633189
Erlotinib & Ramucirumab
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nakagawa et al. 2019 (RELAY) | 2016-01-28 to 2018-02-01 | Phase 3 (E-RT-esc) | Erlotinib | Superior PFS (primary endpoint) Median PFS: 19.4 vs 12.4 mo (HR 0.59, 95% CI 0.46-0.76) |
Note: the FDA-recommended dose is only provided for ramucirumab.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 14
- Ramucirumab (Cyramza) 10 mg/kg IV once on day 1
14-day cycles
References
- RELAY: Nakagawa K, Garon EB, Seto T, Nishio M, Ponce Aix S, Paz-Ares L, Chiu CH, Park K, Novello S, Nadal E, Imamura F, Yoh K, Shih JY, Au KH, Moro-Sibilot D, Enatsu S, Zimmermann A, Frimodt-Moller B, Visseren-Grul C, Reck M; RELAY Study Investigators. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Dec;20(12):1655-1669. Epub 2019 Oct 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02411448
- PRO analysis: Yoh K, Atagi S, Reck M, Garon EB, Ponce Aix S, Moro-Sibilot D, Winfree KB, Frimodt-Moller B, Zimmermann A, Visseren-Grul C, Nakagawa K; RELAY investigators. Patient-reported outcomes in RELAY, a phase 3 trial of ramucirumab plus erlotinib versus placebo plus erlotinib in untreated EGFR-mutated metastatic non-small-cell lung cancer. Curr Med Res Opin. 2020 Oct;36(10):1667-1675. Epub 2020 Aug 28. link to original article PubMed
Furmonertinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shi et al. 2022 (FURLONG) | 2019-05-30 to 2019-12-05 | Phase 3 (E-switch-ic) | Gefitinib | Superior PFS (primary endpoint) Median PFS: 20.8 vs 11.1 mo (HR 0.44, 95% CI 0.34-0.58) |
Biomarker eligibility criteria
- FURLONG: EGFR exon 19 deletion or EGFR p.L858R mutation
References
- FURLONG: Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, Liu J, Cao L, Cheng Y, Zhao H, Zhang S, Zang A, Cui J, Feng J, Yang N, Liu F, Jiang Y, Gu C; FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-1028. Epub 2022 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03787992
GCP
GCP: Gefitinib, Carboplatin, Pemetrexed
Regimen variant #1, 4 cycles of carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Noronha et al. 2019 | 2016-2018 | Phase 3 (E-esc) | Gefitinib | Superior PFS (primary endpoint) Median PFS: 16 vs 8 mo (HR 0.51, 95% CI 0.39-0.66) Superior OS (secondary endpoint) Median OS: NYR vs 17 mo (HR 0.45, 95% CI 0.31-0.65) |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day on days 1 to 21
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, 6 cycles of carboplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hosomi et al. 2019 (NEJ009) | 2011-2015 | Phase 3 (E-esc) | Gefitinib | Superior OS (co-primary endpoint) Median OS: 50.9 vs 38.8 mo (HR 0.72, 95% CI 0.55-0.95) |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycle for up to 6 cycles
References
- NEJ009: Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000006340
- Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed CTRI/2016/08/007149
Gefitinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mitsudomi et al. 2009 (WJTOG3405) | 2006-2009 | Phase 3 (E-switch-ooc) | Cisplatin & Docetaxel | Superior PFS (primary endpoint) Median PFS: 9.2 vs 6.3 mo (HR 0.49, 95% CI 0.34-0.71) |
Maemondo et al. 2010 (NEJ002) | 2006-2009 | Phase 3 (E-switch-ooc) | Carboplatin & Paclitaxel | Superior PFS (primary endpoint) Median PFS: 10.8 vs 5.4 mo (HR 0.30, 95% CI 0.22-0.41) |
Urata et al. 2016 (WJOG 5108L) | 2009-2012 | Phase 3 (E-switch-ic) | Erlotinib | Inconclusive whether non-inferior PFS |
Yang et al. 2017 (CTONG 0901) | 2009-2014 | Phase 3 (C) | Erlotinib | Might have inferior PFS |
Douillard et al. 2014 (IFUM) | 2010-2012 | Phase 4 (RT) | ORR: 70% (95% CI: 60.5–78) | |
Park et al. 2016 (LUX-Lung 7) | 2011-2013 | Randomized Phase 2 (C) | Afatinib | Inferior PFS |
Hosomi et al. 2019 (NEJ009) | 2011-2015 | Phase 3 (C) | GCP | Inferior OS |
Cheng et al. 2016 (JMIT) | 2012-2013 | Randomized Phase 2 (C) | P+G | Seems to have inferior PFS |
Patil et al. 2017 | 2012-2016 | Phase 3 (E-switch-ooc) | Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 8.4 vs 5.6 mo (HR 0.66, 95% CI 0.51-0.85) |
Wu et al. 2017 (ARCHER 1050) | 2013-2015 | Phase 3 (C) | Dacomitinib | Seems to have inferior OS1 |
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (C) | Osimertinib | Seems to have inferior OS2 |
Noronha et al. 2019 | 2016-2018 | Phase 3 (C) | GCP | Inferior OS |
Zhao et al. 2021 (CTONG1706) | 2017-08 to 2018-12 | Phase 3 (C) | Apatinib & Gefitinib | Inferior PFS |
Lu et al. 2022 (AENEAS) | 2018-11-30 to 2019-09-06 | Phase 3 (C) | Aumolertinib | Inferior PFS |
Shi et al. 2022 (FURLONG) | 2019-05-30 to 2019-12-05 | Phase 3 (C) | Furmonertinib | Inferior PFS |
Cho et al. 2023 (LASER301) | 2020-02 to 2021-09 | Phase 3 (C) | Lazertinib | Inferior PFS |
1Reported efficacy for ARCHER 1050 is based on the 2021 update.
2Reported efficacy for FLAURA is based on the 2019 update.
Note: these are all trials restricted to EGFR-mutated lung cancer, with the exception of WJOG 5108L, which nevertheless had 72% EGFR-mutated patients.
Biomarker eligibility criteria
- FURLONG: EGFR exon 19 deletion or EGFR p.L858R mutation
References
- WJTOG3405: Mitsudomi T, Morita S, Yatabe Y, Negoro S, Okamoto I, Tsurutani J, Seto T, Satouchi M, Tada H, Hirashima T, Asami K, Katakami N, Takada M, Yoshioka H, Shibata K, Kudoh S, Shimizu E, Saito H, Toyooka S, Nakagawa K, Fukuoka M; West Japan Thoracic Oncology Group. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol. 2010 Feb;11(2):121-8. Epub 2009 Dec 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000539
- Update: Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I, Tsurutani J, Satouchi M, Hirashima T, Atagi S, Shibata K, Saito H, Toyooka S, Yamamoto N, Nakagawa K, Mitsudomi T. Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. Ann Oncol. 2019 Dec 1;30(12):1978-1984. link to original article PubMed
- NEJ002: Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010 Jun 24;362(25):2380-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000376
- HRQoL analysis: Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T. Quality of life with gefitinib in patients with EGFR-mutated non-small cell lung cancer: quality of life analysis of North East Japan Study Group 002 Trial. Oncologist. 2012;17(6):863-70. Epub 2012 May 11. link to original article link to PMC article PubMed
- Update: Inoue A, Kobayashi K, Maemondo M, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Saijo Y, Hagiwara K, Morita S, Nukiwa T; North-East Japan Study Group. Updated overall survival results from a randomized phase III trial comparing gefitinib with carboplatin-paclitaxel for chemo-naïve non-small cell lung cancer with sensitive EGFR gene mutations (NEJ002). Ann Oncol. 2013 Jan;24(1):54-9. Epub 2012 Sep 11. link to original article PubMed
- IFUM: Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. Epub 2013 Nov 21. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01203917
- LUX-Lung 7: Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01466660
- WJOG 5108L: Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized phase III study comparing gefitinib with erlotinib in patients with previously treated advanced lung adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000002014
- JMIT: Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01469000
- CTONG 0901: Yang JJ, Zhou Q, Yan HH, Zhang XC, Chen HJ, Tu HY, Wang Z, Xu CR, Su J, Wang BC, Jiang BY, Bai XY, Zhong WZ, Yang XN, Wu YL. A phase III randomised controlled trial of erlotinib vs gefitinib in advanced non-small cell lung cancer with EGFR mutations. Br J Cancer. 2017 Feb 28;116(5):568-574. Epub 2017 Jan 19. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01024413
- Patil VM, Noronha V, Joshi A, Choughule AB, Bhattacharjee A, Kumar R, Goud S, More S, Ramaswamy A, Karpe A, Pande N, Chandrasekharan A, Goel A, Talreja V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III study of gefitinib or pemetrexed with carboplatin in EGFR-mutated advanced lung adenocarcinoma. ESMO Open. 2017 Apr 27;2(1):e000168. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- ARCHER 1050: Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. Epub 2017 Sep 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01774721
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in overall survival in a randomized study that compared dacomitinib with gefitinib in patients with advanced non-small-cell lung cancer and EGFR-activating mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. Epub 2018 Jun 4. link to original article PubMed
- Update: Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Chawla A, Rosell R, Corral J, Migliorino MR, Pluzanski A, Noonan K, Tang Y, Pastel M, Wilner KD, Wu YL. Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. Drugs. 2021 Feb;81(2):257-266. link to original article link to PMC article PubMed
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
- NEJ009: Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, Takamura K, Hagiwara K, Kobayashi K, Nukiwa T, Inoue A; North-East Japan Study Group. Gefitinib Alone Versus Gefitinib Plus Chemotherapy for Non-Small-Cell Lung Cancer With Mutated Epidermal Growth Factor Receptor: NEJ009 Study. J Clin Oncol. 2020 Jan 10;38(2):115-123. Epub 2019 Nov 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000006340
- Noronha V, Patil VM, Joshi A, Menon N, Chougule A, Mahajan A, Janu A, Purandare N, Kumar R, More S, Goud S, Kadam N, Daware N, Bhattacharjee A, Shah S, Yadav A, Trivedi V, Behel V, Dutt A, Banavali SD, Prabhash K. Gefitinib Versus Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Mutated Lung Cancer. J Clin Oncol. 2020 Jan 10;38(2):124-136. Epub 2019 Aug 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed CTRI/2016/08/007149
- CTONG1706: Zhao H, Yao W, Min X, Gu K, Yu G, Zhang Z, Cui J, Miao L, Zhang L, Yuan X, Fang Y, Fu X, Hu C, Zhu X, Fan Y, Yu Q, Wu G, Jiang O, Du X, Liu J, Gu W, Hou Z, Wang Q, Zheng R, Zhou X, Zhang L. Apatinib Plus Gefitinib as First-Line Treatment in Advanced EGFR-Mutant NSCLC: The Phase III ACTIVE Study (CTONG1706). J Thorac Oncol. 2021 Sep;16(9):1533-1546. Epub 2021 May 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02824458
- AENEAS: Lu S, Dong X, Jian H, Chen J, Chen G, Sun Y, Ji Y, Wang Z, Shi J, Lu J, Chen S, Lv D, Zhang G, Liu C, Li J, Yu X, Lin Z, Yu Z, Wang Z, Cui J, Xu X, Fang J, Feng J, Xu Z, Ma R, Hu J, Yang N, Zhou X, Wu X, Hu C, Zhang Z, Lu Y, Hu Y, Jiang L, Wang Q, Guo R, Zhou J, Li B, Hu C, Tong W, Zhang H, Ma L, Chen Y, Jie Z, Yao Y, Zhang L, Jie W, Li W, Xiong J, Ye X, Duan J, Yang H, Sun M, Sun C, Wei H, Li C, Ali SM, Miller VA, Wu Q. AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations. J Clin Oncol. 2022 Sep 20;40(27):3162-3171. Epub 2022 May 17. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03849768
- FURLONG: Shi Y, Chen G, Wang X, Liu Y, Wu L, Hao Y, Liu C, Zhu S, Zhang X, Li Y, Liu J, Cao L, Cheng Y, Zhao H, Zhang S, Zang A, Cui J, Feng J, Yang N, Liu F, Jiang Y, Gu C; FURLONG investigators. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study. Lancet Respir Med. 2022 Nov;10(11):1019-1028. Epub 2022 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03787992
- LASER301: Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. Epub 2023 Jun 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04248829
Gefitinib & Pemetrexed
P+G: Pemetrexed and Gefitinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cheng et al. 2016 (JMIT) | 2012-2013 | Randomized Phase 2 (E-esc) | Gefitinib | Seems to have superior PFS (primary endpoint) |
Targeted therapy
- Gefitinib (Iressa) 250 mg PO once per day on days 1 to 21
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
References
- JMIT: Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized phase II trial of gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01469000
Icotinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shi et al. 2017 (CONVINCE) | 2013-01 to 2014-08 | Phase 3 (E-switch-ooc) | Cisplatin & Pemetrexed x 4, then Pemetrexed maintenance | Superior PFS (primary endpoint) Median PFS: 11.2 vs 7.9 mo (HR 0.61, 95% CI 0.43-0.87) |
Lu et al. 2023 | 2019-12-24 to 2020-12-18 | Phase 3 (C) | Befotertinib | Inferior PFS |
Note: this drug is only approved in China; eligible patients in CONVINCE had stage IIIB/IV lung adenocarcinoma.
Biomarker eligibility criteria
- CONVINCE: EGFR exon 19 or 21 mutations
- Lu et al. 2023: EGFR exon 19 deletions or exon 21 Leu858Arg mutation
References
- CONVINCE: Shi YK, Wang L, Han BH, Li W, Yu P, Liu YP, Ding CM, Song X, Ma ZY, Ren XL, Feng JF, Zhang HL, Chen GY, Han XH, Wu N, Yao C, Song Y, Zhang SC, Song W, Liu XQ, Zhao SJ, Lin YC, Ye XQ, Li K, Shu YQ, Ding LM, Tan FL, Sun Y. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study. Ann Oncol. 2017 Oct 1;28(10):2443-2450. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01719536
- Lu S, Zhou J, Jian H, Wu L, Cheng Y, Fan Y, Fang J, Chen G, Zhang Z, Lv D, Jiang L, Wu R, Jin X, Zhang X, Zhang J, Xie C, Sun G, Huang D, Cui J, Guo R, Han Z, Chen Z, Liang J, Zhuang W, Hu X, Zang A, Zhang Y, Cang S, Lan Y, Chen X, Liu L, Li X, Chen J, Ma R, Guo Y, Sun P, Tian P, Pan Y, Liu Z, Cao P, Ding L, Wang Y, Yuan X, Wu P. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study. Lancet Respir Med. 2023 Oct;11(10):905-915. Epub 2023 May 24. link to original article PubMed NCT04206072
Lazertinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cho et al. 2023 (LASER301) | 2020-02 to 2021-09 | Phase 3 (E-switch-ic) | Gefitinib | Superior PFS (primary endpoint) Median PFS: 20.6 vs 9.7 mo (HR 0.45, 95% CI 0.34-0.58) |
References
- LASER301: Cho BC, Ahn MJ, Kang JH, Soo RA, Reungwetwattana T, Yang JC, Cicin I, Kim DW, Wu YL, Lu S, Lee KH, Pang YK, Zimina A, Fong CH, Poddubskaya E, Sezer A, How SH, Danchaivijitr P, Kim Y, Lim Y, An T, Lee H, Byun HM, Zaric B. Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301. J Clin Oncol. 2023 Sep 10;41(26):4208-4217. Epub 2023 Jun 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04248829
Osimertinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soria et al. 2017 (FLAURA) | 2014-2016 | Phase 3 (E-RT-switch-ic) | 1a. Erlotinib 1b. Gefitinib |
Superior PFS (primary endpoint) Median PFS: 18.9 vs 10.2 mo (HR 0.46, 95% CI 0.37-0.57) Seems to have superior OS1 (secondary endpoint) Median OS: 38.6 vs 31.8 mo (HR 0.80, 95% CI 0.64-1.00) |
Planchard et al. 2023 (FLAURA2) | 2020-06-01 to 2021-12-22 | Phase 3 (C) | 1a. Carboplatin, Osimertinib, Pemetrexed 1b. Cisplatin, Osimertinib, Pemetrexed |
Inferior PFS |
1Reported efficacy for FLAURA is based on the 2019 update.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R mutation
References
- FLAURA: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. Epub 2017 Nov 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02296125
- Subgroup analysis: Reungwetwattana T, Nakagawa K, Cho BC, Cobo M, Cho EK, Bertolini A, Bohnet S, Zhou C, Lee KH, Nogami N, Okamoto I, Leighl N, Hodge R, McKeown A, Brown AP, Rukazenkov Y, Ramalingam SS, Vansteenkiste J. CNS response to osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer. J Clin Oncol. 2018 Nov 20;36(33):3290-7. Epub 2018 Aug 28. link to original article PubMed
- Update: Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, Zhou C, Reungwetwattana T, Cheng Y, Chewaskulyong B, Shah R, Cobo M, Lee KH, Cheema P, Tiseo M, John T, Lin MC, Imamura F, Kurata T, Todd A, Hodge R, Saggese M, Rukazenkov Y, Soria JC; FLAURA Investigators. Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. 2020 Jan 2;382(1):41-50. Epub 2019 Nov 21. link to original article PubMed
- FLAURA2: Planchard D, Jänne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. Epub 2023 Nov 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04035486
- ECOG-ACRIN EA5182: NCT04181060
- MARIPOSA: NCT04487080
Advanced or metastatic disease, EGFR inhibitor-exposed
ABCP
ABCP: Atezolizumab, Bevacizumab, Carboplatin, Paclitaxel
Regimen variant #1, 4 cycles then maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (E-esc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Superior PFS (primary endpoint) Median PFS: 8.48 vs 5.62 mo (HR 0.62, 95% CI 0.45-0.86) |
Prior treatment criteria
- Progression or intolerance to one or more EGFR TKIs
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 or 5.5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 175 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, 6 cycles then maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (E-esc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Superior PFS (primary endpoint) Median PFS: 8.48 vs 5.62 mo (HR 0.62, 95% CI 0.45-0.86) |
Prior treatment criteria
- Progression or intolerance to one or more EGFR TKIs
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 or 5.5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 6: 175 mg/m2 IV once on day 1
21-day cycles
References
- ATTLAS: Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03991403
Afatinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Katakami et al. 2013 (LUX-Lung 4) | 2009-2011 | Phase 2 | ORR: 8% (95% CI: 3-18) |
Note: In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants.
Prior treatment criteria
- Progression 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, taken at least 1 hour before eating food
Continued indefinitely
References
- 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00711594
Afatinib & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hata et al. 2018 (ABC Study) | 2014-2017 | Phase 2 |
Targeted therapy
- Afatinib (Gilotrif) 30 mg PO once per day on days 1 to 21
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
21-day cycles
References
- ABC Study: Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, Morita S, Negoro S; Hanshin Oncology Group F. Afatinib plus bevacizumab combination after acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: Multicenter, single-arm, phase 2 trial (ABC Study). Cancer. 2018 Oct 1;124(19):3830-3838. Epub 2018 Sep 7. link to original article PubMed UMIN000014710
Afatinib & Cetuximab
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Janjigian et al. 2014 (BI 1200.71) | 2010-2013 | Phase 1b | ORR: 29% |
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day on days 1 to 14
- Cetuximab (Erbitux) 500 mg IV once on day 1
14-day cycles
References
- BI 1200.71: Janjigian YY, Smit EF, Groen HJ, Horn L, Gettinger S, Camidge DR, Riely GJ, Wang B, Fu Y, Chand VK, Miller VA, Pao W. Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations. Cancer Discov. 2014 Sep;4(9):1036-45. Epub 2014 Jul 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01090011
Carboplatin & Pemetrexed
Regimen variant #1, AUC 5 x 4 with pemetrexed maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2024 (CheckMate 722) | 2017-03 to 2020-06 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Nivolumab 1b. Cisplatin, Pemetrexed, Nivolumab |
Might have inferior PFS (primary endpoint) Median PFS: 5.4 vs 5.6 mo (HR 1.33, 95% CI 1.00-1.79) |
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (C) | ABCP | Inferior PFS |
Passaro et al. 2023 (MARIPOSA-2) | 2021-12 to 2023-04 | Phase 3 (C) | 1. Carboplatin, Pemetrexed, Amivantamab 2. Carboplatin, Lazertinib, Pemetrexed, Amivantamab |
Inferior PFS |
Awaiting publication (HERTHENA-Lung02) | 2022-ongoing | Phase 3 (C) | Patritumab-DXd | TBD if different primary endpoint of PFS |
Note: this was the lower bound of carboplatin dosing in CheckMate 722.
Prior treatment criteria
- MARIPOSA-2: Progression after osimertinib
- HERTHENA-Lung02: Progression after first-line EGFR TKI therapy
- ATTLAS: Progression or intolerance to one or more EGFR TKIs
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, AUC 5 x 6 with pemetrexed maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (C) | ABCP | Inferior PFS |
Prior treatment criteria
- Progression or intolerance to one or more EGFR TKIs
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #3, AUC 6 x 4 with pemetrexed maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2024 (CheckMate 722) | 2017-03 to 2020-06 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Nivolumab 1b. Cisplatin, Pemetrexed, Nivolumab |
Might have inferior PFS (primary endpoint) Median PFS: 5.4 vs 5.6 mo (HR 1.33, 95% CI 1.00-1.79) |
Note: this was the upper bound of carboplatin dosing in CheckMate 722.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 6 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
References
- MARIPOSA-2: Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04988295
- CheckMate 722: Mok T, Nakagawa K, Park K, Ohe Y, Girard N, Kim HR, Wu YL, Gainor J, Lee SH, Chiu CH, Kim SW, Yang CT, Wu CL, Wu L, Lin MC, Samol J, Ichikado K, Wang M, Zhang X, Sylvester J, Li S, Forslund A, Yang JC. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722. J Clin Oncol. 2024 Apr 10;42(11):1252-1264. Epub 2024 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02864251
- ATTLAS: Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03991403
- HERTHENA-Lung02: NCT05338970
Carboplatin, Pemetrexed, Amivantamab
Regimen variant #1, lower-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Passaro et al. 2023 (MARIPOSA-2) | 2021-12 to 2023-04 | Phase 3 (E-esc) | 1. Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 6.3 vs 4.2 mo (HR 0.48, 95% CI 0.36-0.64) |
2. Carboplatin, Lazertinib, Pemetrexed, Amivantamab | Not formally compared |
Note: This amivantamab dosage was for patients weighing less than 80 kg.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15
- Cycle 2: 1400 mg IV once on day 1
- Cycle 3 onwards: 1750 mg IV once on day 1
21-day cycles
Regimen variant #2, higher-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Passaro et al. 2023 (MARIPOSA-2) | 2021-12 to 2023-04 | Phase 3 (E-esc) | 1. Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 6.3 vs 4.2 mo (HR 0.48, 95% CI 0.36-0.64) |
2. Carboplatin, Lazertinib, Pemetrexed, Amivantamab | Not formally compared |
Note: This amivantamab dosage was for patients weighing 80 kg or more.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15
- Cycle 2: 1750 mg IV once on day 1
- Cycle 3 onwards: 2100 mg IV once on day 1
21-day cycles
References
- MARIPOSA-2: Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04988295
Carboplatin, Lazertinib, Pemetrexed, Amivantamab
Regimen variant #1, lower-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Passaro et al. 2023 (MARIPOSA-2) | 2021-12 to 2023-04 | Phase 3 (E-esc) | 1. Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 8.3 vs 4.2 mo (HR 0.44, 95% CI 0.35-0.56) |
2. Carboplatin, Pemetrexed, Amivantamab | Not formally compared |
Note: This amivantamab dosage was for patients weighing less than 80 kg. Due to excess toxicity in this arm, the lazertinib was not started until cycle 5, after a protocol modification.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1050 mg IV once on day 2, then 1400 mg IV once per day on days 8 & 15
- Cycle 2: 1400 mg IV once on day 1
- Cycle 3 onwards: 1750 mg IV once on day 1
- Lazertinib (Leclaza) as follows:
- Cycle 5 onwards: 240 mg PO once per day on days 1 to 21
21-day cycles
Regimen variant #2, higher-dose amivantamab
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Passaro et al. 2023 (MARIPOSA-2) | 2021-12 to 2023-04 | Phase 3 (E-esc) | 1. Carboplatin & Pemetrexed | Superior PFS (primary endpoint) Median PFS: 8.3 vs 4.2 mo (HR 0.44, 95% CI 0.35-0.56) |
2. Carboplatin, Pemetrexed, Amivantamab | Not formally compared |
Note: This amivantamab dosage was for patients weighing 80 kg or more. Due to excess toxicity in this arm, the lazertinib was not started until cycle 5, after a protocol modification.
Biomarker eligibility criteria
- EGFR exon 19 deletion or p.L858R
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Amivantamab (Rybrevant) as follows:
- Cycle 1: 350 mg IV once on day 1, then 1400 mg IV once on day 2, then 1750 mg IV once per day on days 8 & 15
- Cycle 2: 1750 mg IV once on day 1
- Cycle 3 onwards: 2100 mg IV once on day 1
- Lazertinib (Leclaza) as follows:
- Cycle 5 onwards: 240 mg PO once per day on days 1 to 21
21-day cycles
References
- MARIPOSA-2: Passaro A, Wang J, Wang Y, Lee SH, Melosky B, Shih JY, Wang J, Azuma K, Juan-Vidal O, Cobo M, Felip E, Girard N, Cortot AB, Califano R, Cappuzzo F, Owen S, Popat S, Tan JL, Salinas J, Tomasini P, Gentzler RD, William WN Jr, Reckamp KL, Takahashi T, Ganguly S, Kowalski DM, Bearz A, MacKean M, Barala P, Bourla AB, Girvin A, Greger J, Millington D, Withelder M, Xie J, Sun T, Shah S, Diorio B, Knoblauch RE, Bauml JM, Campelo RG, Cho BC; MARIPOSA-2 Investigators. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024 Jan;35(1):77-90. Epub 2023 Oct 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT04988295
Cisplatin & Pemetrexed
Regimen variant #1, 70/500 x 4 with pemetrexed maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (C) | ABCP | Inferior PFS |
Prior treatment criteria
- Progression or intolerance to one or more EGFR TKIs
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 70 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, 70/500 x 6 with pemetrexed maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2023 (ATTLAS) | 2019-08-27 to 2022-03-11 | Phase 3 (C) | ABCP | Inferior PFS |
Prior treatment criteria
- Progression or intolerance to one or more EGFR TKIs
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 6: 70 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
Regimen variant #3, 75/500, limited duration
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soria et al. 2015 (IMPRESS) | 2012-03-29 to 2013-12-20 | Phase 3 (C) | Cisplatin, Pemetrexed, Gefitinib | Did not meet primary endpoint of PFS |
Prior treatment criteria
- Progression after first-line gefitinib
Biomarker eligibility criteria
- EGFR mutation positive
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive therapy
- (as described in Scagliotti et al. 2008):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to pemetrexed
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for pemetrexed."
21-day cycle for 4 to 6 cycles
Regimen variant #4, 75/500 x 4 with pem maintenance
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2024 (CheckMate 722) | 2017-03 to 2020-06 | Phase 3 (C) | 1a. Carboplatin, Pemetrexed, Nivolumab 1b. Cisplatin, Pemetrexed, Nivolumab |
Might have inferior PFS (primary endpoint) Median PFS: 5.4 vs 5.6 mo (HR 1.33, 95% CI 1.00-1.79) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
21-day cycles
References
- IMPRESS: Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. Epub 2015 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01544179
- Update: Mok TSK, Kim SW, Wu YL, Nakagawa K, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Shi X, Rukazenkov Y, Haddad V, Thress KS, Soria JC. Gefitinib plus chemotherapy versus chemotherapy in epidermal growth factor receptor mutation-positive non-small-cell lung cancer resistant to first-line gefitinib (IMPRESS): overall survival and biomarker analyses. J Clin Oncol. 2017 Dec 20;35(36):4027-4034. Epub 2017 Oct 2. link to original article PubMed
- CheckMate 722: Mok T, Nakagawa K, Park K, Ohe Y, Girard N, Kim HR, Wu YL, Gainor J, Lee SH, Chiu CH, Kim SW, Yang CT, Wu CL, Wu L, Lin MC, Samol J, Ichikado K, Wang M, Zhang X, Sylvester J, Li S, Forslund A, Yang JC. Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor-Mutated Metastatic Non-Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722. J Clin Oncol. 2024 Apr 10;42(11):1252-1264. Epub 2024 Jan 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02864251
- ATTLAS: Park S, Kim TM, Han JY, Lee GW, Shim BY, Lee YG, Kim SW, Kim IH, Lee S, Kim YJ, Park JH, Park SG, Lee KH, Kang EJ, Kim JW, Shin SH, Ock CY, Nam BH, Lee J, Jung HA, Sun JM, Lee SH, Ahn JS, Ahn MJ. Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04). J Clin Oncol. 2024 Apr 10;42(11):1241-1251. Epub 2023 Oct 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03991403
- HERTHENA-Lung02: NCT05338970
Advanced or metastatic disease, EGFR p.T790M mutation
Carboplatin & Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2016 (AURA3) | 2014-08 to 2015-09 | Phase 3 (C) | Osimertinib | Inferior PFS |
Prior treatment criteria
- Progression after first-line EGFR TKI therapy
Biomarker eligibility criteria
- EGFR p.T790M mutation
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 15 to 60 minutes once on day 1, given second
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1, given first
Supportive therapy
- (Ardizzoni et al. 2012 contained more details):
- Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO twice per day on the day before, the day of, and day after each dose of pemetrexed
- Folic acid (Folate) 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, 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, to be given throughout pemetrexed therapy
21-day cycle for 4 to 6 cycles
Subsequent treatment
- Optional pemetrexed maintenance
References
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02151981
- PRO analysis: Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. link to original article PubMed
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. link to original article PubMed
Cisplatin & Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2016 (AURA3) | 2014-08 to 2015-09 | Phase 3 (C) | Osimertinib | Inferior PFS |
Prior treatment criteria
- Progression after first-line EGFR TKI therapy
Biomarker eligibility criteria
- EGFR p.T790M mutation
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive therapy
- (as described in Scagliotti et al. 2008):
- Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to pemetrexed
- Folic acid (Folate) 1 mg PO once per day
- In Sequist et al. 2013: Patients "received Folic acid (Folate), vitamin B12, and dexamethasone, as per package recommendations for pemetrexed."
21-day cycle for 4 to 6 cycles
Subsequent treatment
- AURA3, patients without disease progression after 4 cycles: Optional pemetrexed maintenance
References
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02151981
- PRO analysis: Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. link to original article PubMed
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. link to original article PubMed
Docetaxel & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Nie et al. 2018 (QingdaoCH20161101) | 2015-04 to 2016-05 | Phase 3 (C) | Osimertinib | Inferior PFS |
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.
Biomarker eligibility criteria
- EGFR p.T790M mutation
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
21-day cycles
References
- QingdaoCH20161101: Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02959749
Osimertinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jänne et al. 2015 (AURA) | 2013 to not reported | Phase 1/2 (RT) | ||
Goss et al. 2016 (AURA2) | 2014 | Phase 2 (RT) | ||
Mok et al. 2016 (AURA3) | 2014-08 to 2015-09 | Phase 3 (E-RT-switch-ooc) | 1a. Carboplatin & Pemetrexed 1b. Cisplatin & Pemetrexed |
Superior PFS (primary endpoint) Median PFS: 10.1 vs 4.4 mo (HR 0.30, 95% CI 0.23-0.41) Did not meet secondary endpoint of OS1 Median OS: 26.8 vs 22.5 mo (HR 0.87, 95% CI 0.67-1.12) |
Nie et al. 2018 (QingdaoCH20161101) | 2015-04 to 2016-05 | Phase 3 (E-switch-ooc) | Docetaxel & Bevacizumab | Superior PFS (primary endpoint) Median PFS: 10.2 vs 3 mo (HR 0.23, 95% CI 0.12-0.38) Did not meet secondary endpoint of OS (HR 0.79, 95% CI 0.38-1.60) |
1Reported efficacy for OS endpoint in AURA3 is based on the 2020 update.
Prior treatment criteria
- AURA3: Progression after first-line EGFR TKI therapy
Biomarker eligibility criteria
- AURA3: EGFR p.T790M mutation
References
- AURA: Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01802632
- Update: Yang JC, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, Blackhall F, Haggstrom D, Yoh K, Novello S, Gold K, Hirashima T, Lin CC, Mann H, Cantarini M, Ghiorghiu S, Jänne PA. Osimertinib in Pretreated T790M-Positive Advanced Non-Small-Cell Lung Cancer: AURA Study Phase II Extension Component. J Clin Oncol. 2017 Apr 20;35(12):1288-1296. Epub 2017 Feb 21. link to original article PubMed
- Pooled update: Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. link to original article PubMed NCT01802632
- Pooled update: Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Jänne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. Epub 2018 Dec 4. link to original article PubMed
- AURA2: Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. Epub 2016 Oct 14. link to original article PubMed NCT02094261
- Pooled subgroup analysis: Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crinò L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Jänne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. link to original article PubMed
- Pooled update: Ahn MJ, Tsai CM, Shepherd FA, Bazhenova L, Sequist LV, Hida T, Yang JCH, Ramalingam SS, Mitsudomi T, Jänne PA, Mann H, Cantarini M, Goss G. Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-term follow-up from a pooled analysis of 2 phase 2 studies. Cancer. 2019 Mar 15;125(6):892-901. Epub 2018 Dec 4. link to original article PubMed
- AURA3: Mok TS, Wu YL, Ahn MJ, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. Epub 2016 Dec 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02151981
- PRO analysis: Lee CK, Novello S, Rydén A, Mann H, Mok T. Patient-Reported Symptoms and Impact of Treatment With Osimertinib Versus Chemotherapy in Advanced Non-Small-Cell Lung Cancer: The AURA3 Trial. J Clin Oncol. 2018 Jun 20;36(18):1853-1860. Epub 2018 May 7. link to original article PubMed
- Subgroup analysis: Wu YL, Ahn MJ, Garassino MC, Han JY, Katakami N, Kim HR, Hodge R, Kaur P, Brown AP, Ghiorghiu D, Papadimitrakopoulou VA, Mok TSK. CNS efficacy of osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase III trial (AURA3). J Clin Oncol. 2018 Sep 10;36(26):2702-2709. Epub 2018 Jul 30. link to original article PubMed
- Update: Papadimitrakopoulou VA, Mok TS, Han JY, Ahn MJ, Delmonte A, Ramalingam SS, Kim SW, Shepherd FA, Laskin J, He Y, Akamatsu H, Theelen WSME, Su WC, John T, Sebastian M, Mann H, Miranda M, Laus G, Rukazenkov Y, Wu YL. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020 Nov;31(11):1536-1544. Epub 2020 Aug 27. link to original article PubMed
- QingdaoCH20161101: Nie K, Zhang Z, Zhang C, Geng C, Zhang L, Xu X, Liu S, Wang S, Zhuang X, Lan K, Ji Y. Osimertinib compared docetaxel-bevacizumab as third-line treatment in EGFR T790M mutated non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:5-11. Epub 2018 Apr 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02959749