Non-small cell lung cancer
Page editor | Section editor | ||
---|---|---|---|
Eric K. Singhi, MD MD Anderson Cancer Center Houston, TX, USA |
Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN, USA |
Are you looking for a regimen but can't find it here? It is possible that we've moved it to the historical regimens page or to one of the histology-specific, biomarker-specific, or site-specific pages that are linked below. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
There are several related dedicated pages:
- Histology-specific:
- Biomarker-specific:
- Site-specific:
Last updated on 2024-09-06: 120 regimens on this page
235 variants on this page
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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
- 2024: Daly et al. Management of Stage III Non-Small Cell Lung Cancer: ASCO Rapid Recommendation Update PubMed
- 2023: Jaiyesimi et al. Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO Living Guideline, Version 2022.3 PubMed
- 2020: Schneider et al. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline PubMed
- 2017: Hanna et al. Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2015: Masters et al. Systemic therapy for stage IV non–small-cell lung cancer: American Society of Clinical Oncology clinical practice guideline update PubMed
- 2009: Azzoli et al. American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer PubMed
ASCO/CCO
Current
- 2021: Hanna et al. Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO and OH (CCO) Joint Guideline Update PubMed
- 2020: Hanna et al. Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update PubMed
- 2017: Kris et al. Adjuvant systemic therapy and adjuvant radiation therapy for stage I to IIIA completely resected non–small-cell lung cancers: American Society of Clinical Oncology/Cancer Care Ontario clinical practice guideline update PubMed
ESMO
- 2023: Hendriks et al. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up PubMed
- 2018: Planchard et al. Metastatic Non-Small-Cell Lung Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2016: Novello et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2014: Reck et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Peters et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: D'Addario et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2017: Postmus et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Vansteenkiste et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Crinò et al. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2015: Eberhardt et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer PubMed
- 2014: Vansteenkiste et al. 2nd ESMO Consensus Conference on Lung Cancer: early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up PubMed
- 2014: Besse et al. 2nd ESMO Consensus Conference on Lung Cancer: non-small-cell lung cancer first-line/second and further lines of treatment in advanced disease PubMed
- 2014: Kerr et al. Second ESMO consensus conference on lung cancer: pathology and molecular biomarkers for non-small-cell lung cancer PubMed
- 2009: D'Addario & Felip. Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: D'Addario & Felip. Non-small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Felip et al. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of non-small-cell lung cancer (NSCLC) PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of non-small-cell lung cancer (NSCLC) PubMed
KSMO/ESMO
- 2020: Park et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with locally-advanced unresectable non-small-cell lung cancer: a KSMO-ESMO initiative endorsed by CSCO, ISMPO, JSMO, MOS, SSO and TOS PubMed
- 2019: Wu et al. Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO-ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS PubMed
ISRS
- 2023: Mayinger et al. Stereotactic Body Radiotherapy for Lung Oligo-metastases: Systematic Review and International Stereotactic Radiosurgery Society Practice Guidelines PubMed
- 2023: Yan et al. Stereotactic body radiotherapy for Ultra-Central lung Tumors: A systematic review and Meta-Analysis and International Stereotactic Radiosurgery Society practice guidelines PubMed
NCCN
- NCCN Guidelines - Non-Small Cell Lung Cancer
- 2024: Riely et al. Non–Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2017: Ettinger et al. Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2015: Ettinger et al. Non-Small Cell Lung Cancer, Version 6.2015. PubMed
- 2014: Ettinger et al. Non–Small Cell Lung Cancer, Version 1.2015 PubMed
- 2013: Ettinger et al. Non-small cell lung cancer, version 2.2013. PubMed
- 2012: Ettinger et al. Non-small cell lung cancer. PubMed
- 2008: Ettinger et al. Non-small cell lung cancer. PubMed
- 2006: Ettinger et al. Non-small cell lung cancer clinical practice guidelines in oncology. PubMed
- 2004: Authors not listed. Non-small cell lung cancer. Clinical practice guidelines in oncology. PubMed
SITC
Definitive therapy for early/localized disease
Nivolumab & RT
Nivolumab & RT: Nivolumab & Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chang et al. 2023 (MDACC 2016-0737) | 2017-06-30 to 2022-03-22 | Randomized Phase 2 (E-esc) | RT | Superior EFS48 (primary endpoint) EFS48: 77% vs 53% (HR 0.42, 95% CI 0.22-0.80) |
Immunotherapy
- Nivolumab (Opdivo) as follows:
- Cycle 1: 480 mg IV once on day 1, started on the same day or within 36 hours of the first SABR fraction
- Cycles 2 to 4: 480 mg IV once on day 1
Radiotherapy
- Concurrent stereotactic ablative radiotherapy (SABR)
28-day cycle for 4 cycles
References
- MDACC 2016-0737: Chang JY, Lin SH, Dong W, Liao Z, Gandhi SJ, Gay CM, Zhang J, Chun SG, Elamin YY, Fossella FV, Blumenschein G, Cascone T, Le X, Pozadzides JV, Tsao A, Verma V, Welsh JW, Chen AB, Altan M, Mehran RJ, Vaporciyan AA, Swisher SG, Balter PA, Fujimoto J, Wistuba II, Feng L, Lee JJ, Heymach JV. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet. 2023 Sep 9;402(10405):871-881. Epub 2023 Jul 18. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT03110978
Radiation therapy
RT: Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chang et al. 2023 (MDACC 2016-0737) | 2017-06-30 to 2022-03-22 | Randomized Phase 2 (E-esc) | Nivolumab & RT | Inferior EFS48 |
Awaiting publication (KEYNOTE-867) | 2019-ongoing | Phase 3 (C) | Pembrolizumab & RT | TBD if different co-primary endpoints of EFS/OS |
Awaiting publication (PACIFIC-4) | 2019-ongoing | Phase 3 (C) | Durvalumab & RT | TBD if different primary endpoint of PFS |
Awaiting publication (SWOG S1914) | 2020-ongoing | Phase 3 (C) | Atezolizumab & RT | TBD if different primary endpoint of OS |
References
- MDACC 2016-0737: Chang JY, Lin SH, Dong W, Liao Z, Gandhi SJ, Gay CM, Zhang J, Chun SG, Elamin YY, Fossella FV, Blumenschein G, Cascone T, Le X, Pozadzides JV, Tsao A, Verma V, Welsh JW, Chen AB, Altan M, Mehran RJ, Vaporciyan AA, Swisher SG, Balter PA, Fujimoto J, Wistuba II, Feng L, Lee JJ, Heymach JV. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet. 2023 Sep 9;402(10405):871-881. Epub 2023 Jul 18. link to original article link to PMC article PubMed NCT03110978
- KEYNOTE-867: NCT03924869
- PACIFIC-4: NCT03833154
- SWOG S1914: NCT04214262
Neoadjuvant therapy
Carboplatin & Paclitaxel (CP)
CP: Carboplatin & Paclitaxel
Regimen variant #1, 5/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. 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
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #2, 5/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Provencio et al. 2023 (NADIM II) | 2019-06 to 2021-02 | Randomized Phase 2 (C) | CP & Nivolumab | Seems to have inferior OS (secondary endpoint) |
Note: CheckMate 816 had additional comparator options depending on histology; see the respective histology-specific pages for more details. 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
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #3, 6/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. 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
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #4, 6/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. 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
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02998528
- NADIM II: Provencio M, Nadal E, González-Larriba JL, Martínez-Martí A, Bernabé R, Bosch-Barrera J, Casal-Rubio J, Calvo V, Insa A, Ponce S, Reguart N, de Castro J, Mosquera J, Cobo M, Aguilar A, López Vivanco G, Camps C, López-Castro R, Morán T, Barneto I, Rodríguez-Abreu D, Serna-Blasco R, Benítez R, Aguado de la Rosa C, Palmero R, Hernando-Trancho F, Martín-López J, Cruz-Bermúdez A, Massuti B, Romero A. Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):504-513. Epub 2023 Jun 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03838159
Carboplatin & Paclitaxel (CP) & Nivolumab
CP & Nivolumab: Carboplatin, Paclitaxel, Nivolumab
Regimen variant #1, 5/175/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
Subsequent treatment
Regimen variant #2, 5/200/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Provencio et al. 2023 (NADIM II) | 2019-06 to 2021-02 | Randomized Phase 2 (E-esc) | CP | Seems to have superior OS (secondary endpoint) OS24: 85% vs 63.6% (HR 0.43, 95% CI 0.19-0.98) Seems to have superior pCR rate (primary endpoint) |
Note: CheckMate 816 had additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
Subsequent treatment
- CheckMate 816: Complete resection
- NADIM II: Complete resection, then adjuvant nivolumab if R0 resection
Regimen variant #3, 6/175/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
Subsequent treatment
Regimen variant #4, 6/200/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02998528
- NADIM II: Provencio M, Nadal E, González-Larriba JL, Martínez-Martí A, Bernabé R, Bosch-Barrera J, Casal-Rubio J, Calvo V, Insa A, Ponce S, Reguart N, de Castro J, Mosquera J, Cobo M, Aguilar A, López Vivanco G, Camps C, López-Castro R, Morán T, Barneto I, Rodríguez-Abreu D, Serna-Blasco R, Benítez R, Aguado de la Rosa C, Palmero R, Hernando-Trancho F, Martín-López J, Cruz-Bermúdez A, Massuti B, Romero A. Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):504-513. Epub 2023 Jun 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03838159
Cisplatin & Docetaxel (DC)
DC: Docetaxel & Cisplatin
Regimen variant #1, 60/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #2, 75/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #3, 85/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pless et al. 2015 (SAKK 16/00) | 2001-2012 | Phase 3 (C) | Cisplatin & Docetaxel, then RT | Did not meet primary endpoint of EFS |
Eligibility criteria
- Stage IIIA or N2 NSCLC
Chemotherapy
- Docetaxel (Taxotere) 85 mg/m2 IV once on day 1
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- SAKK 16/00: Pless M, Stupp R, Ris HB, Stahel RA, Weder W, Thierstein S, Gerard MA, Xyrafas A, Früh M, Cathomas R, Zippelius A, Roth A, Bijelovic M, Ochsenbein A, Meier UR, Mamot C, Rauch D, Gautschi O, Betticher DC, Mirimanoff RO, Peters S; SAKK Lung Cancer Project Group. Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial. Lancet. 2015 Sep 12;386(9998):1049-56. Epub 2015 Aug 11. Erratum in: Lancet. 2015 Sep 12;386(9998):1040. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00030771
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT02998528
Cisplatin & Docetaxel (DC) & Durvalumab
DC & Durvalumab: Docetaxel, Cisplatin, Durvalumab
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rothschild et al. 2021 (SAKK 16/14) | 2016-2019 | Phase 2 |
Eligibility criteria
- Stage IIIA(N2) NSCLC
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 3: 100 mg/m2 IV once on day 1
- Docetaxel (Taxotere) as follows:
- Cycles 1 to 3: 85 mg/m2 IV once on day 1
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 4 & 5: 750 mg IV once on day 1
21-day cycle for 3 cycles, then 14-day cycle for 2 cycles
Subsequent treatment
- Complete resection, then adjuvant durvalumab
References
- SAKK 16/14: Rothschild SI, Zippelius A, Eboulet EI, Savic Prince S, Betticher D, Bettini A, Früh M, Joerger M, Lardinois D, Gelpke H, Mauti LA, Britschgi C, Weder W, Peters S, Mark M, Cathomas R, Ochsenbein AF, Janthur WD, Waibel C, Mach N, Froesch P, Buess M, Bohanes P, Godar G, Rusterholz C, Gonzalez M, Pless M; Swiss Group for Clinical Cancer Research (SAKK). SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial. J Clin Oncol. 2021 Sep 10;39(26):2872-2880. Epub 2021 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02572843
Cisplatin & Docetaxel (DC) & Nivolumab
DC & Nivolumab: Docetaxel, Cisplatin, Nivolumab
Regimen variant #1, 60/75/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #2, 75/75/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02998528
Cisplatin & Etoposide (EP)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Thomas et al. 2008 (GLCCG 01/95) | 1995-2003 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cisplatin (Platinol) 55 mg/m2 IV once per day on days 1 & 4
- Etoposide (Vepesid) 100 mg/m2 (route not specified) once per day on days 1 to 4
21-day cycle for 3 cycles
Subsequent treatment
- Complete surgical resection followed by adjuvant RT versus neoadjuvant Carboplatin, Vindesine, RT followed by surgical resection
References
- GLCCG 01/95: Thomas M, Rübe C, Hoffknecht P, Macha HN, Freitag L, Linder A, Willich N, Hamm M, Sybrecht GW, Ukena D, Deppermann KM, Dröge C, Riesenbeck D, Heinecke A, Sauerland C, Junker K, Berdel WE, Semik M; German Lung Cancer Cooperative Group. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol. 2008 Jul;9(7):636-48. Epub 2008 Jun 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00176137
Cisplatin & Gemcitabine (GC)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Scagliotti et al. 2011 (CHEST) | 2000-2004 | Phase 3 (E-esc) | Surgery alone | Seems to have superior PFS (primary endpoint) Median PFS: 4 vs 2.2 y (aHR 0.70, 95% CI 0.50-0.97) Superior OS (secondary endpoint) Median OS: 7.8 vs 4.8 y (aHR 0.63, 95% CI 0.43-0.92) |
Awaiting publication (IMpower030) | 2018-ongoing | Phase 3 (C) | 1a. Carboplatin, nab-Paclitaxel, Atezolizumab 1b. Carboplatin, Pemetrexed, Atezolizumab 1c. GC & Atezolizumab 1d. Pem-Cis & Atezolizumab |
TBD if different primary endpoint of EFS |
Eligibility criteria
- CHEST: Stage IB to IIIA NSCLC
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given at least 4 hours after gemcitabine
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for varying durations: 3 cycles (CHEST); 4 cycles (IMpower030)
Subsequent treatment
- Complete resection, 2 to 6 weeks after last dose of chemotherapy
References
- CHEST: Scagliotti GV, Pastorino U, Vansteenkiste JF, Spaggiari L, Facciolo F, Orlowski TM, Maiorino L, Hetzel M, Leschinger M, Visseren-Grul C, Torri V. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol. 2012 Jan 10;30(2):172-8. Epub 2011 Nov 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00191126
- IMpower030: NCT03456063
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
Regimen variant #1, 75/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- 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 3 cycles
Subsequent treatment
Regimen variant #2, 75/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (C) | 1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab |
Inferior EFS |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02998528
Cisplatin & Vinorelbine (CVb) & Nivolumab
CVb & Nivolumab: Cisplatin, Vinorelbine, Nivolumab
Regimen variant #1, 75/25/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
Regimen variant #2, 75/30/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Forde et al. 2022 (CheckMate 816) | 2017-2019 | Phase 3 (E-RT-esc) | 1a. CP 1b. CVb 1c. DC |
Superior EFS (co-primary endpoint) Median EFS: 31.6 vs 20.8 mo (HR 0.63, 97.38% CI 0.43-0.91) Superior pCR rate (co-primary endpoint) pCR rate: 24% vs 2.2% (OR 13.94, 99% CI 3.49-55.75) |
Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. The timing of vinorelbine was not specified in the supplementary materials; this timing is typical.
Biomarker eligibility criteria
- CheckMate 816: No sensitizing EGFR or ALK mutations
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 3 cycles
Subsequent treatment
References
- CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02998528
Adjuvant therapy
Atezolizumab monotherapy
Regimen variant #1, q2wk
FDA-recommended dose |
Note: This is not the dose/schedule used in the registration trial.
Preceding treatment
- Resection, then adjuvant platinum-based chemotherapy
Regimen variant #2, q3wk
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Felip et al. 2021 (IMpower010) | 2015-2018 | Phase 3 (E-RT-esc) | Best supportive care | Seems to have superior DFS (primary endpoint) Median DFS: NYR vs 37.2 mo (HR 0.81, 95% CI 0.67-0.99) Did not meet secondary endpoint of OS Median OS: NYR vs NYR (sHR 0.995, 95% CI 0.78-1.28) |
Preceding treatment
- IMpower010, nonsquamous: Resection, then adjuvant Cisplatin & Vinorelbine x 4 or DC x 4 or GC x 4 or Cisplatin & Pemetrexed x 4
- IMpower010, squamous: Resection, then adjuvant Cisplatin & Vinorelbine x 4 or DC x 4 or GC x 4
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycle for up to 16 cycles (1 year)
Regimen variant #3, q4wk
FDA-recommended dose |
Note: This is not the dose/schedule used in the registration trial.
Preceding treatment
- Resection, then adjuvant platinum-based chemotherapy
References
- IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02486718
- Update: Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. Epub 2023 Jul 17. link to original article PubMed
Carboplatin & Paclitaxel (CP)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Strauss et al. 2008 (CALGB 9633) | 1996-2003 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS |
Preceding treatment
- Lobectomy or pneumonectomy, within 4 to 8 weeks
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 45 to 60 minutes once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle for 4 cycles
References
- CALGB 9633: Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00002852
- IFCT 0002: Westeel V, Quoix E, Puyraveau M, Lavolé A, Braun D, Laporte S, Bigay-Game L, Pujol JL, Ozenne G, Rivière A, Douillard JY, Lebeau B, Debieuvre D, Poudenx M, David P, Molinier O, Zalcman G, Lemarié E, Morin F, Depierre A, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. A randomised trial comparing preoperative to perioperative chemotherapy in early-stage non-small-cell lung cancer (IFCT 0002 trial). Eur J Cancer. 2013 Aug;49(12):2654-64. Epub 2013 Jun 1. link to original article PubMed NCT00198354
Cisplatin & Docetaxel (DC)
DC: Docetaxel & Cisplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Barlesi et al. 2015 | 2004-2007 | Phase 3 (E-switch-ic) | Cisplatin & Gemcitabine | Did not meet primary endpoint of QoL | |
Wakelee et al. 2017 (ECOG-ACRIN E1505) | 2007-2013 | Phase 3 (C) | 1a. DC & Bevacizumab 1b. GC & Bevacizumab 1c. Cisplatin, Pemetrexed, Bevacizumab 1d. Cisplatin, Vinorelbine, Bevacizumab |
Did not meet primary endpoint of OS Median OS: NYR vs 85.8 mo (HR 1.01, 95% CI 0.84-1.22) |
Preceding treatment
- Barlesi et al. 2015: Complete R0 resection, within 8 weeks
- ECOG-ACRIN E1505: Complete surgical resection, within 6 to 12 weeks
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 varying durations: 3 cycles (Barlesi et al. 2015); 4 cycles (ECOG-ACRIN E1505)
References
- Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00324805
- IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02486718
- Update: Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. Epub 2023 Jul 17. link to original article PubMed
Cisplatin & Etoposide (EP)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arriagada et al. 2004 (IALT) | 1995-2000 | Phase 3 (E-esc) | Observation | Seems to have superior OS (primary endpoint) OS60: 44.5% vs 40.4% (HR 0.86, 95% CI 0.76-0.98) |
Preceding treatment
- Complete surgical resection, within 60 days
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
28-day cycle for 4 cycles
References
- IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article does not contain dosing details in manuscript PubMed NCT00002823
- Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine & Cisplatin
Regimen variant #1, 75/1200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wakelee et al. 2017 (ECOG-ACRIN E1505) | 2007-2013 | Phase 3 (C) | 1a. DC & Bevacizumab 1b. GC & Bevacizumab 1c. Cisplatin, Pemetrexed, Bevacizumab 1d. Cisplatin, Vinorelbine, Bevacizumab |
Did not meet primary endpoint of OS Median OS: NYR vs 85.8 mo (HR 1.01, 95% CI 0.84-1.22) |
Preceding treatment
- Complete surgical resection, within 6 to 12 weeks
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Regimen variant #2, 75/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Barlesi et al. 2015 | 2004-2007 | Phase 3 (E-switch-ic) | Cisplatin & Docetaxel | Did not meet primary endpoint of QoL | |
Felip et al. 2021 (IMpower010) | 2015-2018 | Non-randomized part of phase 3 RCT |
Eligibility criteria
- Stage IB–III NSCLC
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for varying durations: 3 cycles (Barlesi et al. 2015); 4 cycles (IMpower010)
Subsequent treatment
- IMpower010: Atezolizumab maintenance versus best supportive care
References
- Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00324805
- IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02486718
- Update: Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. Epub 2023 Jul 17. link to original article PubMed
- ACCIO: NCT04267848
Cisplatin & Pemetrexed
CPx: Cisplatin & Pemetrexed
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Kreuter et al. 2013 (TREAT) | 2006-2009 | Randomized Phase 2 (E-switch-ic) | Cisplatin & Vinorelbine | Did not meet secondary endpoint of OS1 | Superior clinical feasibility rate |
Wakelee et al. 2017 (ECOG-ACRIN E1505) | 2007-2013 | Phase 3 (C) | 1a. DC & Bevacizumab 1b. GC & Bevacizumab 1c. Cisplatin, Pemetrexed, Bevacizumab 1d. Cisplatin, Vinorelbine, Bevacizumab |
Did not meet primary endpoint of OS Median OS: NYR vs 85.8 mo (HR 1.01, 95% CI 0.84-1.22) |
|
Groen et al. 2019 (NVALT-8) | 2007-2013 | Phase 3 (C) | CPx & Nadroparin | Did not meet primary endpoint of RFS Median RFS: 37.7 vs 65.2 mo (HR 1.30, 95% CI 0.88-1.89) |
1Reported efficacy for TREAT is based on the 2016 update.
Note: In TREAT, this treatment was intended for pathologically confirmed NSCLC stages (according to the TNM staging system version 6) IB, IIA, IIB or T3N1.
Preceding treatment
- TREAT & NVALT-8: Complete surgical resection, within 4 to 6 weeks
- ECOG-ACRIN E1505: Complete surgical resection, within 6 to 12 weeks
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 4 cycles
References
- TREAT: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG Leuven Lung Cancer Group. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349089
- Update: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. link to original article PubMed
- ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00324805
- NVALT-8: Groen HJM, van der Heijden EHFM, Klinkenberg TJ, Biesma B, Aerts J, Verhagen A, Kloosterziel C, Pieterman R, van den Borne B, Smit HJM, Hoekstra O, Schramel FMNH, van der Noort V, van Tinteren H, Smit EF, Dingemans AC; NVALT Study Group. Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study. Br J Cancer. 2019 Aug;121(5):372-377. Epub 2019 Jul 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NTR1250/1217
- IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02486718
- Update: Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. Epub 2023 Jul 17. link to original article PubMed
Cisplatin & Vinblastine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arriagada et al. 2004 (IALT) | 1995-2000 | Phase 3 (E-esc) | Observation | Seems to have superior OS (primary endpoint) OS60: 44.5% vs 40.4% (HR 0.86, 95% CI 0.76-0.98) |
Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vinblastine schedule is extrapolated from regimen information in Table 1 in which vinblastine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.
Preceding treatment
- Complete surgical resection, within 60 days
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once per day on days 1, 22, 43, 64
- Vinblastine (Velban) 4 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 43, 57
12-week course
References
- IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article does not contain dosing details in manuscript PubMed NCT00002823
- Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed
Cisplatin & Vindesine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Arriagada et al. 2004 (IALT) | 1995-2000 | Phase 3 (E-esc) | Observation | Seems to have superior OS (primary endpoint) OS60: 44.5% vs 40.4% (HR 0.86, 95% CI 0.76-0.98) |
Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vindesine schedule is extrapolated from regimen information in Table 1 in which vindesine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.
Preceding treatment
- Complete surgical resection, within 60 days
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once per day on days 1, 22, 43, 64
- Vindesine (Eldisine) 3 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 43, 57
12-week course
References
- IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article does not contain dosing details in manuscript PubMed NCT00002823
- Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
Regimen variant #1, cisplatin 50 mg/m2, 2 weeks out of 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Winton et al. 2005 (JBR.10) | 1994-2001 | Phase 3 (E-esc) | Observation | Superior OS (primary endpoint) Median OS: 94 vs 73 mo (HR 0.69, 95% CI 0.52-0.91) |
|
Kreuter et al. 2013 (TREAT) | 2006-2009 | Randomized Phase 2 (C) | Cisplatin & Pemetrexed | Did not meet secondary endpoint of OS1 | Superior clinical feasibility rate |
1Reported efficacy for TREAT is based on the 2016 update.
Preceding treatment
- JBR.10: Complete surgical resection, within 6 weeks
- TREAT: Complete surgical resection, within 4 to 6 weeks
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
Regimen variant #2, cisplatin 75 mg/m2, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wakelee et al. 2017 (ECOG-ACRIN E1505) | 2007-2013 | Phase 3 (C) | 1a. DC & Bevacizumab 1b. GC & Bevacizumab 1c. Cisplatin, Pemetrexed, Bevacizumab 1d. Cisplatin, Vinorelbine, Bevacizumab |
Did not meet primary endpoint of OS Median OS: NYR vs 85.8 mo (HR 1.01, 95% CI 0.84-1.22) |
Preceding treatment
- Complete surgical resection, within 6 to 12 weeks
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Regimen variant #3, cisplatin 100 mg/m2, q4wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Douillard et al. 2006 (ANITA) | 1994-2000 | Phase 3 (E-esc) | Observation | Seems to have superior OS (primary endpoint) Median OS: 65.7 vs 43.7 mo (aHR 0.80, 95% CI 0.66-0.96) |
Arriagada et al. 2004 (IALT) | 1995-2000 | Phase 3 (E-esc) | Observation | Seems to have superior OS (primary endpoint) OS60: 44.5% vs 40.4% (HR 0.86, 95% CI 0.76-0.98) |
Preceding treatment
- IALT: Complete surgical resection, within 60 days
- ANITA: Complete surgical resection
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15, 22
28-day cycle for 4 cycles
References
- IALT: Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article does not contain dosing details in manuscript PubMed NCT00002823
- Update: Arriagada R, Dunant A, Pignon JP, Bergman B, Chabowski M, Grunenwald D, Kozlowski M, Le Péchoux C, Pirker R, Pinel MI, Tarayre M, Le Chevalier T. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol. 2010 Jan 1;28(1):35-42. Epub 2009 Nov 23. link to original article PubMed
- JBR.10: Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. link to original article PubMed NCT00002583
- Update: Butts CA, Ding K, Seymour L, Twumasi-Ankrah P, Graham B, Gandara D, Johnson DH, Kesler KA, Green M, Vincent M, Cormier Y, Goss G, Findlay B, Johnston M, Tsao MS, Shepherd FA. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol. 2010 Jan 1;28(1):29-34. Epub 2009 Nov 23. link to original article link to PMC article PubMed
- ANITA: Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Rodrigues Pereira J, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. link to original article PubMed NCT00576914
- TREAT: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators; AIO Lung Cancer Study Group; LLCG. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349089
- Update: Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt WE, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Griesinger F, Thomas M; TREAT investigators. Three-year follow-up of a randomized phase II trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine (the TREAT study). J Thorac Oncol. 2016 Jan;11(1):85-93. link to original article PubMed
- ECOG-ACRIN E1505: Wakelee HA, Dahlberg SE, Keller SM, Tester WJ, Gandara DR, Graziano SL, Adjei AA, Leighl NB, Aisner SC, Rothman JM, Patel JD, Sborov MD, McDermott SR, Perez-Soler R, Traynor AM, Butts C, Evans T, Shafqat A, Chapman AE, Kasbari SS, Horn L, Ramalingam SS, Schiller JH; ECOG-ACRIN. Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1610-1623. Epub 2017 Nov 9. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00324805
- IMpower010: Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, Luft A, Akopov A, Martinez-Marti A, Kenmotsu H, Chen YM, Chella A, Sugawara S, Voong D, Wu F, Yi J, Deng Y, McCleland M, Bennett E, Gitlitz B, Wakelee H; IMpower010 Investigators. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021 Oct 9;398(10308):1344-1357. Epub 2021 Sep 20. Erratum in: Lancet. 2021 Sep 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02486718
- Update: Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, Belleli R, McNally V, Srivastava MK, Bennett E, Gitlitz BJ, Wakelee HA. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023 Oct;34(10):907-919. Epub 2023 Jul 17. link to original article PubMed
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Provencio et al. 2023 (NADIM II) | 2019-06 to 2021-02 | Non-randomized part of randomized phase 2 RCT |
Preceding treatment
- Neoadjuvant CP & Nivolumab x 3, then R0 surgical resection
References
- NADIM II: Provencio M, Nadal E, González-Larriba JL, Martínez-Martí A, Bernabé R, Bosch-Barrera J, Casal-Rubio J, Calvo V, Insa A, Ponce S, Reguart N, de Castro J, Mosquera J, Cobo M, Aguilar A, López Vivanco G, Camps C, López-Castro R, Morán T, Barneto I, Rodríguez-Abreu D, Serna-Blasco R, Benítez R, Aguado de la Rosa C, Palmero R, Hernando-Trancho F, Martín-López J, Cruz-Bermúdez A, Massuti B, Romero A. Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):504-513. Epub 2023 Jun 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03838159
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Brien et al. 2022 (PEARLS) | 2016-2020 | Phase 3 (E-RT-esc) | Placebo | Superior DFS (primary endpoint) Median DFS: 53.6 vs 42 mo (HR 0.76, 95% CI 0.63-0.91) |
Preceding treatment
- Complete surgical resection
References
- PEARLS: O'Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, Esteban E, Isla D, Martinez-Marti A, Faehling M, Tsuboi M, Lee JS, Nakagawa K, Yang J, Samkari A, Keller SM, Mauer M, Jha N, Stahel R, Besse B, Peters S; EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 Investigators. Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1274-1286. Epub 2022 Sep 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02504372
UFT monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamaguchi et al. 2021 (WJTOG0101) | 2001-2005 | Phase 3 (C) | Gemcitabine | Did not meet primary endpoint of OS OS60: 68.8% vs 70% (HR 1.05, 95% CI 0.81-1.37) |
Eligibility criteria
- Stage IB-IIIA NSCLC, with complete resection
Preceding treatment
Chemotherapy
- Tegafur and uracil (UFT) 250 mg/m2/day PO (rounded up or down to the nearest 100 mg)
28-day cycle for 13 cycles (1 year)
References
- WJTOG0101: Yamaguchi M, Tada H, Mitsudomi T, Seto T, Yokoi K, Katakami N, Nakagawa K, Oda M, Ohta M, Sawa T, Yamashita M, Ikeda N, Saka H, Higashiyama M, Nomori H, Semba H, Negoro S, Chiba Y, Shimokawa M, Fukuoka M, Nakanishi Y; West Japan Thoracic Oncology Group (WJTOG). Phase III study of adjuvant gemcitabine compared with adjuvant uracil-tegafur in patients with completely resected pathological stage IB-IIIA non-small cell lung cancer (WJTOG0101). Int J Clin Oncol. 2021 Dec;26(12):2216-2223. Epub 2021 Aug 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00139971
Induction chemotherapy for locally advanced disease
Carboplatin & Paclitaxel (CP)
PC: Paclitaxel & Carboplatin
Regimen variant #1, 6/200 without cap
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Belani et al. 2005 (LAMP) | 1998-02 to 2001-06 | Phase 2 | ||
Vokes et al. 2007 (CALGB 39801) | 1998-2002 | Phase 3 (E-esc) | No induction | Did not meet primary endpoint of OS50% |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 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 2 cycles
Regimen variant #2, 6/200 with cap
Study | Dates of enrollment | Evidence |
---|---|---|
Huber et al. 2006 (CTRT99/97) | 1997-2002 | Non-randomized part of phase 3 RCT |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 60 minutes once on day 1, given second
- Paclitaxel (Taxol) 200 mg/m2 (maximum dose of 440 mg) IV over 3 hours once on day 1, given first
21-day cycle for 2 cycles
Subsequent treatment
- Definitive Paclitaxel & RT versus RT
Regimen variant #3, 6/225
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hoang et al. 2012 (ECOG 3598) | 2000-2006 | Phase 3 (C) | See link | See link |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 225 mg/m2 IV once on day 1
21-day cycle for 2 cycles
Subsequent treatment
- Definitive CP & RT
References
- LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. Epub 2005 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CTRT99/97: Huber RM, Flentje M, Schmidt M, Pöllinger B, Gosse H, Willner J, Ulm K; Bronchial Carcinoma Therapy Group. Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group. J Clin Oncol. 2006 Sep 20;24(27):4397-404. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CALGB 39801: Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; CALGB. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003387
- ECOG 3598: Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00004859
Cisplatin & Vinblastine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Dillman et al. 1990 (CALGB 8433) | 1984-1987 | Phase 3 (E-esc) | No induction | Seems to have superior OS1 (primary endpoint) |
Sause et al. 1995 (RTOG 88-08) | 1989-1992 | Phase 3 (E-esc) | No induction | Seems to have superior OS (primary endpoint) |
Curran et al. 2011 (RTOG 9410) | 1994-1998 | Phase 3 (C) | See link | See link |
1Reported efficacy for CALGB 8433 is based on the 1996 update.
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 29
- Vinblastine (Velban) 5 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29
7-week course
Subsequent treatment
- Definitive RT x 6000 to 6300 cGy
References
- CALGB 8433: Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC, Carey RW, Frei EF 3rd, Green MR. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med. 1990 Oct 4;323(14):940-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III non-small-cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst. 1996 Sep 4;88(17):1210-5. link to original article PubMed
- RTOG 88-08: Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, Emami B, Curran WJ, Byhardt RW, Turrisi AT, Dar AR, Cox JD. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern Cooperative Oncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst. 1995 Feb 1;87(3):198-205. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, Emami B, Curran W Jr, Byhardt R, Dar AR, Turrisi A 3rd. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest. 2000 Feb;117(2):358-64. link to original article PubMed
- RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01134861
Definitive therapy for locally advanced disease
Carboplatin & Paclitaxel (CP) & RT
CP & RT: Carboplatin, Paclitaxel, Radiation Therapy
PC & RT: Paclitaxel, Carboplatin, Radiation Therapy
Regimen variant #1, 2/40/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yamamoto et al. 2010 (WJTOG0105) | 2001-2005 | Phase 3 (E-switch-ic) | 1. MVP & RT | Inconclusive whether non-inferior OS (primary endpoint) |
2. Carboplatin, Irinotecan, RT | Not compared |
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29, 36
- Paclitaxel (Taxol) 40 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- Concurrent radiation therapy, 6000 cGy
6-week course
Subsequent treatment
- CP consolidation x 2
Regimen variant #2, 2/45/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lu et al. 2010 (ID99-303) | 2000-2006 | Phase 3 (C) | PC, AE-941, RT | Did not meet primary endpoint of OS Median OS: 15.6 vs 14.4 mo |
Hoang et al. 2012 (ECOG 3598) | 2000-2006 | Phase 3 (C) | See link | See link |
Bradley et al. 2015 (RTOG 0617) | 2007-2011 | Phase 3 (C) | 1. CP, Cetuximab, concurrent RT | Did not meet primary endpoint of OS |
2. CP & RT; high-dose RT 3. CP, Cetuximab, RT; high-dose RT |
Superior OS (primary endpoint) | |||
Liang et al. 2017 | 2007-2011 | Phase 3 (E-switch-ic) | EP & RT | Might have inferior OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Preceding treatment
- ECOG 3598 & ID99-303: PC induction x 2
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36 given second
- Paclitaxel (Taxol) 45 mg/m2 IV over 1 to 3 hours once per day on days 1, 8, 15, 22, 29, 36 given first
Radiotherapy
- Concurrent radiation therapy: 200 cGy fractions x 30 fractions (total of 6000 cGy)
6-week course
Subsequent treatment
- RTOG 0617: PC consolidation x 2
Regimen variant #3, 2/45/63
Study | Dates of enrollment | Evidence |
---|---|---|
Belani et al. 2005 (LAMP) | 1998-02 to 2001-06 | Phase 2 |
Preceding treatment
- PC induction
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, given second
- Paclitaxel (Taxol) 45 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, given first
Radiotherapy
- Concurrent radiation therapy: 180 cGy fractions x 25 fractions, then 200 cGy fractions x 9 fractions
7-week course
Subsequent treatment
- PC consolidation x 2
Regimen variant #4, 2/50/66
Study | Dates of enrollment | Evidence |
---|---|---|
Vokes et al. 2007 (CALGB 39801) | 1998-2002 | Non-randomized part of phase 3 RCT |
Preceding treatment
- PC induction x 2 versus no induction
Chemotherapy
- Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, given second
- Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36, 43, given first
Radiotherapy
- Concurrent radiation therapy, 6600 cGy
7-week course
References
- LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. Epub 2005 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CALGB 39801: Vokes EE, Herndon JE 2nd, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, Atkins JN, Watson DM, Akerley W, Green MR; CALGB. Induction chemotherapy followed by chemoradiotherapy compared with chemoradiotherapy alone for regionally advanced unresectable stage III non-small-cell lung cancer: Cancer and Leukemia Group B. J Clin Oncol. 2007 May 1;25(13):1698-704. Epub 2007 Apr 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003387
- ID99-303: Lu C, Lee JJ, Komaki R, Herbst RS, Feng L, Evans WK, Choy H, Desjardins P, Esparaz BT, Truong MT, Saxman S, Kelaghan J, Bleyer A, Fisch MJ. Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst. 2010 Jun 16;102(12):859-65. Epub 2010 May 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00005838
- WJTOG0105: Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144053
- Update: Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Yamamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. link to original article link to PMC article PubMed
- ECOG 3598: Hoang T, Dahlberg SE, Schiller JH, Mehta MP, Fitzgerald TJ, Belinsky SA, Johnson DH. Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study. J Clin Oncol. 2012 Feb 20;30(6):616-22. Epub 2012 Jan 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00004859
- RTOG 0617: Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00533949
- Update: Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. link to original article link to PMC article PubMed
- Dataset: Project Data Sphere
- Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01494558
- ECOG-ACRIN EA5181: NCT04092283
- MS200647_0005: NCT03840902
- PACIFIC 2: NCT03519971
Carboplatin, Vinorelbine, RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Strøm et al. 2013 (Conrad) | 2006-2011 | Phase 3 (E-esc) | Carboplatin & Vinorelbine | Superior OS (primary endpoint) Median OS: 12.6 vs 9.7 mo |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 60 minutes once on day 1
- Vinorelbine (Navelbine) 60 mg/m2 PO once per day on days 1 & 8
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 2: 280 cGy per day on days 1 to 5, 8 to 12, 15 to 19 (4200 cGy in 15 fractions)
21-day cycle for 4 cycles
References
- Conrad: Strøm HH, Bremnes RM, Sundstrøm SH, Helbekkmo N, Fløtten O, Aasebø U; Norwegian Lung Cancer Study Group. Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2013 Sep 17;109(6):1467-75. Epub 2013 Aug 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN63778716
Carboplatin & RT
Carboplatin & RT: Carboplatin & Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Atagi et al. 2012 (JCOG0301) | 2003-2010 | Phase 3 (E-esc) | RT | Seems to have superior OS (primary endpoint) Median OS: 22.4 vs 16.9 mo (HR 0.68, 95.4% CI 0.47-0.98) |
Chemotherapy
- Carboplatin (Paraplatin) 30 mg/m2 IV over 30 minutes once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26
Radiotherapy
- Concurrent radiation therapy: 6000 cGy in 30 fractions
6-week course
References
- JCOG0301: Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; JCOG Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00132665
Cisplatin & RT
Cisplatin & RT: Cisplatin & Radiation Therapy
Regimen variant #1, weekly cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schaake-Koning et al. 1992 | 1984-1989 | Phase 3 (E-esc) | 1. Cisplatin & RT; weekly cisplatin | Did not meet primary endpoint of OS |
2. RT | Superior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 6 mg/m2 IV once per day on days 1 to 5, 8 to 12, 36 to 40, 43 to 47
Radiotherapy
- Concurrent radiation therapy 300 cGy per day on days 1 to 5, 8 to 12, then 250 cGy per day on days 36 to 40, 43 to 47
7-week course
Regimen variant #2, q3wk cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Blanke et al. 1995 | 1986-1992 | Phase 3 (E-esc) | RT | Might have superior PFS (co-primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once per day on days 1, 22, 43
Radiotherapy
- Concurrent radiation therapy 6000 to 6500 cGy total tumor dose in daily fractions of 180 to 200 cGy
6.5-week course
References
- Schaake-Koning C, van den Bogaert W, Dalesio O, Festen J, Hoogenhout J, van Houtte P, Kirkpatrick A, Koolen M, Maat B, Nijs A, Renaud A, Rodrigus P, Schuster-Uitterhoeve L, Sculier JP, van Zandwijk N, Bartelink H. Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med. 1992 Feb 20;326(8):524-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Blanke C, Ansari R, Mantravadi R, Gonin R, Tokars R, Fisher W, Pennington K, O'Connor T, Rynard S, Miller M, Einhorn L. Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small-cell lung cancer: a Hoosier Oncology Group protocol. J Clin Oncol. 1995 Jun;13(6):1425-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
Cisplatin, Docetaxel, RT
DC & RT: Docetaxel, Cisplatin, Radiation Therapy
DP & RT: Docetaxel, Platinol (Cisplatin), Radiation Therapy
Regimen variant #1, 20/20
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oh et al. 2013 (KASLC 0401) | 2005-2007 | Phase 3 (C) | 1. TP & RT 2. GC & RT |
Did not meet primary endpoint of ORR |
Ahn et al. 2015 (KCSG-LU05-04) | 2005-2011 | Non-randomized part of phase 3 RCT |
Note: In KCSG-LU05-04, no benefit was observed to giving post-definitive consolidation.
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
- Docetaxel (Taxotere) 20 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- Concurrent radiation therapy, 200 cGy fractions x 33 fractions (total dose: 6600 cGy)
6-week course
Subsequent treatment
- KCSG-LU05-04: Cisplatin & Docetaxel consolidation versus no further treatment
Regimen variant #2, 40/40
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Segawa et al. 2010 (OLCSG 0007) | 2000-2005 | Phase 3 (E-switch-ic) | MVP & RT | Might have superior OS24 (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 1, 8, 29, 36
- Docetaxel (Taxotere) 40 mg/m2 IV once per day on days 1, 8, 29, 36
Radiotherapy
- Concurrent radiation therapy, 200 cGy fractions x 30 fractions (total dose: 6000 cGy)
6-week course
References
- OLCSG 0007: Segawa Y, Kiura K, Takigawa N, Kamei H, Harita S, Hiraki S, Watanabe Y, Sugimoto K, Shibayama T, Yonei T, Ueoka H, Takemoto M, Kanazawa S, Takata I, Nogami N, Hotta K, Hiraki A, Tabata M, Matsuo K, Tanimoto M. Phase III trial comparing docetaxel and cisplatin combination chemotherapy with mitomycin, vindesine, and cisplatin combination chemotherapy with concurrent thoracic radiotherapy in locally advanced non-small-cell lung cancer: OLCSG 0007. J Clin Oncol. 2010 Jul 10;28(20):3299-306. Epub 2010 Jun 7. link to original article dosing details in abstract have been reviewed by our editors PubMed UMIN000000085
- KASLC 0401: Oh IJ, Kim KS, Kim YC, Ban HJ, Kwon YS, Kim YI, Lim SC, Chung WK, Nam TK, Song JY, Yoon MS, Ahn SJ. A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401. Cancer Chemother Pharmacol. 2013 Dec;72(6):1247-54. Epub 2013 Oct 5. link to original article dosing details in abstract have been reviewed by our editors PubMed
- KCSG-LU05-04: Ahn JS, Ahn YC, Kim JH, Lee CG, Cho EK, Lee KC, Chen M, Kim DW, Kim HK, Min YJ, Kang JH, Choi JH, Kim SW, Zhu G, Wu YL, Kim SR, Lee KH, Song HS, Choi YL, Sun JM, Jung SH, Ahn MJ, Park K. Multinational randomized phase III trial with or without consolidation chemotherapy using docetaxel and cisplatin after concurrent chemoradiation in inoperable stage III non-small-cell lung cancer: KCSG-LU05-04. J Clin Oncol. 2015 Aug 20;33(24):2660-6. Epub 2015 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00326378
Cisplatin, Etoposide, RT
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
Regimen variant #1, 4500 cGy with response-adapted treatment
Study | Dates of enrollment | Evidence |
---|---|---|
Albain et al. 2002 (SWOG 9019) | 1992-1995 | Phase 2 |
Albain et al. 2009 (RTOG 93-09) | 1994-2001 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1, 8, 29, 36
- Etoposide (Vepesid) 50 mg/m2 IV once per day on days 1 to 5, 29 to 33
Radiotherapy
- Concurrent radiation therapy, 180 cGy fractions x 25 fractions (total dose: 4500 cGy), to start within 24 hours of cycle 1 day 1
8-week course
Subsequent treatment
- SWOG 9019: Patients were re-imaged with CT scan (bone scan and head imaging were only done if patients had new symptoms), and those without progression or new metastatic disease received an additional 200 cGy per day x 8 fractions for a total of 6100 cGy administered overall
- RTOG 93-09: Additional radiation to 6100 cGy followed by EP consolidation versus surgery followed by EP consolidation
Regimen variant #2, 6000 to 6600 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kelly et al. 2008 (SWOG S0023) | 2001-2005 | Non-randomized part of phase 3 RCT | ||
Hanna et al. 2008 (HOG Lun 01-24) | 2002-2006 | Non-randomized part of phase 3 RCT | ||
Liang et al. 2017 | 2007-2011 | Phase 3 (C) | PC & RT | Might have superior OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 1, 8, 29, 33
- Etoposide (Vepesid) 50 mg/m2 IV once per day on days 1 to 5, 29 to 33
Radiotherapy
- Concurrent radiation therapy, 180 to 200 cGy fractions x 30 to 33 fractions (total dose: 6000 to 6600 cGy)
6- to 6.5-week course
Subsequent treatment
- SWOG S0023: Docetaxel consolidation x 3, then gefitinib maintenance versus placebo
- HOG Lun 01-24: Docetaxel consolidation versus observation
- Liang et al. 2017: Optional consolidation chemotherapy
- MS200647_0005: Durvalumab consolidation
Regimen variant #3, 6600 cGy, split cisplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fournel et al. 2005 (NPC 95-01) | 1996-2000 | Phase 3 (E-switch-ic) | Cisplatin & Vinorelbine, then RT | Did not meet primary endpoint of OS |
Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 to 5, 29 to 33
- Etoposide (Vepesid) 50 mg/m2 IV once per day on days 1 to 5, 29 to 33
Radiotherapy
- Concurrent radiation therapy, 200 cGy fractions x 33 fractions (total dose: 6600 cGy)
6.5-week course
Subsequent treatment
- Cisplatin & Vinorelbine consolidation
Regimen variant #4, 6960 cGy (hyperfractionated)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Curran et al. 2011 (RTOG 9410) | 1994-1998 | Phase 3 (E-switch-ic) | 1. Cisplatin, Vinblastine, RT | Did not meet primary endpoint of OS |
2. Cisplatin & Vinblastine, then RT | Might have superior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 29, 36
- Etoposide (Vepesid) by the following BSA-based criteria:
- 1.7 m2 or more: 50 mg PO twice per day on days 1 to 5, 8 to 12, 29 to 33, 36 to 40
- Less than 1.7 m2: 75 mg PO once per day on days 1 to 5, 8 to 12, 29 to 33, 36 to 40
Radiotherapy
- Concurrent radiation therapy, 120 cGy fractions (total dose: 6960 cGy), twice per day for 5 days per week, starting on cycle 1 day 1
6-week course
References
- SWOG 9019: Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Schild SE, Stella PJ, Geyer SM, Bonner JA, Marks RS, McGinnis WL, Goetz SP, Kuross SA, Mailliard JA, Kugler JW, Schaefer PL, Jett JR. Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002 Oct 1;54(2):370-8. link to original article PubMed
- NPC 95-01: Fournel P, Robinet G, Thomas P, Souquet PJ, Léna H, Vergnenégre A, Delhoume JY, Le Treut J, Silvani JA, Dansin E, Bozonnat MC, Daurés JP, Mornex F, Pérol M; Groupe Lyon-Saint-Etienne d'Oncologie Thoracique; Groupe Français de Pneumo-Cancérologie. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie NPC 95-01 Study. J Clin Oncol. 2005 Sep 1;23(25):5910-7. Epub 2005 Aug 8. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SWOG S0023: Kelly K, Chansky K, Gaspar LE, Albain KS, Jett J, Ung YC, Lau DH, Crowley JJ, Gandara DR. Phase III trial of maintenance gefitinib or placebo after concurrent chemoradiotherapy and docetaxel consolidation in inoperable stage III non-small-cell lung cancer: SWOG S0023. J Clin Oncol. 2008 May 20;26(15):2450-6. Epub 2008 Mar 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00020709
- HOG Lun 01-24: Hanna N, Neubauer M, Yiannoutsos C, McGarry R, Arseneau J, Ansari R, Reynolds C, Govindan R, Melnyk A, Fisher W, Richards D, Bruetman D, Anderson T, Chowhan N, Nattam S, Mantravadi P, Johnson C, Breen T, White A, Einhorn L; Hoosier Oncology Group; US Oncology. Phase III study of cisplatin, etoposide, and concurrent chest radiation with or without consolidation docetaxel in patients with inoperable stage III non-small-cell lung cancer: the Hoosier Oncology Group and US Oncology. J Clin Oncol. 2008 Dec 10;26(35):5755-60. Epub 2008 Nov 10. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00216125
- RTOG 93-09: Albain KS, Swann RS, Rusch VW, Turrisi AT 3rd, Shepherd FA, Smith C, Chen Y, Livingston RB, Feins RH, Gandara DR, Fry WA, Darling G, Johnson DH, Green MR, Miller RC, Ley J, Sause WT, Cox JD. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009 Aug 1;374(9687):379-86. Epub 2009 Jul 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00002550
- RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01134861
- Liang J, Bi N, Wu S, Chen M, Lv C, Zhao L, Shi A, Jiang W, Xu Y, Zhou Z, Wang W, Chen D, Hui Z, Lv J, Zhang H, Feng Q, Xiao Z, Wang X, Liu L, Zhang T, Du L, Chen W, Shyr Y, Yin W, Li J, He J, Wang L. Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial. Ann Oncol. 2017 Apr 1;28(4):777-783. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01494558
- MS200647_0005: NCT03840902
- PACIFIC 2: NCT03519971
Cisplatin, Pemetrexed, RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (MS200647_0005) | 2019-ongoing | Phase 3 (C) | 1a. CP, Bintrafusp alfa, RT 1b. Cisplatin, Pemetrexed, Bintrafusp alfa, RT 1c. EP, Bintrafusp alfa, RT |
TBD if different primary endpoint of PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once per day on days 1, 22, 43
- Pemetrexed (Alimta) 500 mg/m2 IV once per day on days 1, 22, 43
Radiotherapy
- Concurrent IMRT, 200 cGy fractions x 30 (total dose: 6000 cGy)
9-week course
Subsequent treatment
- Durvalumab consolidation
References
- MS200647_0005: dosing details on CT.gov have been reviewed by our editors NCT03840902
Cisplatin, Vinblastine, RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Curran et al. 2011 (RTOG 9410) | 1994-1998 | Phase 3 (E-switch-ic) | 1. Cisplatin, Etoposide, RT | Did not meet primary endpoint of OS |
2. Cisplatin & Vinblastine, then RT | Seems to have superior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 29
- Vinblastine (Velban) 5 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy
5-week course
References
- RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01134861
Cisplatin, Vinorelbine, RT
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Eberhardt et al. 2015 (ESPATUE) | 2004-2013 | Phase 3 (E-switch-ooc) | Surgery | Did not meet primary endpoint of OS |
Preceding treatment
- Cisplatin & Paclitaxel induction
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once per day on days 2 & 9
- Vinorelbine (Navelbine) 20 mg/m2 IV once per day on days 2 & 9
Radiotherapy
- Concurrent radiation therapy 150 cGy twice per day for 30 fractions (4500 cGy total)
21-day course
References
- ESPATUE: Eberhardt WE, Pöttgen C, Gauler TC, Friedel G, Veit S, Heinrich V, Welter S, Budach W, Spengler W, Kimmich M, Fischer B, Schmidberger H, De Ruysscher D, Belka C, Cordes S, Hepp R, Lütke-Brintrup D, Lehmann N, Schuler M, Jöckel KH, Stamatis G, Stuschke M. Phase III Study of Surgery Versus Definitive Concurrent Chemoradiotherapy Boost in Patients With Resectable Stage IIIA(N2) and Selected IIIB Non-Small-Cell Lung Cancer After Induction Chemotherapy and Concurrent Chemoradiotherapy (ESPATUE). J Clin Oncol. 2015 Dec 10;33(35):4194-201. Epub 2015 Nov 2. link to original article dosing details in abstract have been reviewed by our editors PubMed
Radiation therapy
RT: Radiation Therapy
Regimen variant #1, 2000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ball et al. 1997 | 1988-1993 | Phase 3 (C) | 5-FU & RT | Seems to have inferior OS |
Regimen variant #2, 4500 cGy + 1800 cGy boost (6300 cGy total)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Curran et al. 2011 (RTOG 9410) | 1994-1998 | Phase 3 (C) | See link | See link |
Belani et al. 2005 (LAMP) | 1998-02 to 2001-06 | Phase 2 |
Preceding treatment
- LAMP: Induction Carboplatin & Paclitaxel x 2
- RTOG 9410: Induction Cisplatin & Vinblastine x 5 wk
Radiotherapy
- External beam radiotherapy 4500 cGy in 180 cGy fractions x 25 fractions, then 1800 cGy boost in 200 cGy fractions x 9 fractions
7-week course
Regimen variant #3, 6000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Perez et al. 1988 | Not reported | Phase 3 (C) | Levamisole & RT | Did not meet endpoint of OS |
Morton et al. 1991 | 1983-1987 | Phase 3 (C) | MACC & RT | Did not meet primary endpoint of OS |
Clamon et al. 1999 (CALGB 9130) | 1991 to not reported | Phase 3 (C) | Carboplatin & RT | Did not meet primary endpoint of OS |
Bradley et al. 2002 (RTOG 93-04) | 1994-1998 | Phase 3 (C) | Beta-interferon & RT | Did not meet primary endpoint of OS |
Groen et al. 2004 | 1995-1998 | Phase 3 (C) | Carboplatin & RT | Did not meet primary endpoint of OS24 |
Atagi et al. 2012 (JCOG0301) | 2003-2010 | Phase 3 (C) | Carboplatin & RT | Seems to have inferior OS |
Preceding treatment
- CALGB 9130: Induction Cisplatin & Vinblastine x 5 wk
References
- Perez CA, Bauer M, Emami BN, Byhardt R, Brady LW, Doggett RL, Gardner P, Zinninger M. Thoracic irradiation with or without levamisole (NSC #177023) in unresectable non-small cell carcinoma of the lung: a phase III randomized trial of the RTOG. Int J Radiat Oncol Biol Phys. 1988 Dec;15(6):1337-46. link to original article PubMed
- Morton RF, Jett JR, McGinnis WL, Earle JD, Therneau TM, Krook JE, Elliott TE, Mailliard JA, Nelimark RA, Maksymiuk AW, Drummond RG, Laurie JA, Kugler JW, Anderson RT. Thoracic radiation therapy alone compared with combined chemoradiotherapy for locally unresectable non-small cell lung cancer: a randomized, phase III trial. Ann Intern Med. 1991 Nov 1;115(9):681-6. link to original article PubMed
- Ball D, Smith J, Bishop J, Olver I, Davis S, O'Brien P, Bernshaw D, Ryan G, Millward M. A phase III study of radiotherapy with and without continuous-infusion fluorouracil as palliation for non-small-cell lung cancer. Br J Cancer. 1997;75(5):690-7. link to original article link to PMC article PubMed
- CALGB 9130: Clamon G, Herndon J, Cooper R, Chang AY, Rosenman J, Green MR; CALGB; ECOG. Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol. 1999 Jan;17(1):4-11. link to original article PubMed
- RTOG 93-04: Bradley JD, Scott CB, Paris KJ, Demas WF, Machtay M, Komaki R, Movsas B, Rubin P, Sause WT. A phase III comparison of radiation therapy with or without recombinant beta-interferon for poor-risk patients with locally advanced non-small-cell lung cancer (RTOG 93-04). Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1173-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Groen HJ, van der Leest AH, Fokkema E, Timmer PR, Nossent GD, Smit WJ, Nabers J, Hoekstra HJ, Hermans J, Otter R, van Putten JW, de Vries EG, Mulder NH. Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study. Ann Oncol. 2004 Mar;15(3):427-32. link to original article PubMed
- LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. Epub 2005 Aug 8. link to original article dosing details in abstract have been reviewed by our editors PubMed
- RTOG 9410: Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. Erratum in: J Natl Cancer Inst. 2012;104(1):79. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01134861
- JCOG0301: Atagi S, Kawahara M, Yokoyama A, Okamoto H, Yamamoto N, Ohe Y, Sawa T, Ishikura S, Shibata T, Fukuda H, Saijo N, Tamura T; JCOG Lung Cancer Study Group. Thoracic radiotherapy with or without daily low-dose carboplatin in elderly patients with non-small-cell lung cancer: a randomised, controlled, phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol. 2012 Jul;13(7):671-8. Epub 2012 May 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00132665
- SWOG S1914: NCT04214262
Consolidation after definitive therapy for inoperable disease
Carboplatin & Paclitaxel (CP)
Regimen variant #1, 5/200
Study | Dates of enrollment | Evidence |
---|---|---|
Yamamoto et al. 2010 (WJTOG0105) | 2001-2005 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Definitive CP & RT
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 2 cycles
Regimen variant #2, 6/200
Study | Dates of enrollment | Evidence |
---|---|---|
Belani et al. 2005 (LAMP) | 1998-02 to 2001-06 | Phase 2 |
Bradley et al. 2015 (RTOG 0617) | 2007-2011 | Non-randomized part of phase 3 RCT |
Preceding treatment
- Definitive CP & RT
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 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 2 cycles
References
- LAMP: Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. Epub 2005 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- WJTOG0105: Yamamoto N, Nakagawa K, Nishimura Y, Tsujino K, Satouchi M, Kudo S, Hida T, Kawahara M, Takeda K, Katakami N, Sawa T, Yokota S, Seto T, Imamura F, Saka H, Iwamoto Y, Semba H, Chiba Y, Uejima H, Fukuoka M. Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer: West Japan Thoracic Oncology Group WJTOG0105. J Clin Oncol. 2010 Aug 10;28(23):3739-45. Epub 2010 Jul 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144053
- Update: Zenke Y, Tsuboi M, Chiba Y, Tsujino K, Satouchi M, Sawa K, Shimizu J, Daga H, Fujimoto D, Mori M, Aoki T, Sawa T, Omori S, Saka H, Iwamoto Y, Okuno M, Hirashima T, Kashiwabara K, Tachihara M, Yamamoto N, Nakagawa K. Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):904-909. link to original article link to PMC article PubMed
- RTOG 0617: Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol. 2015 Feb;16(2):187-99. Epub 2015 Jan 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00533949
- Update: Bradley JD, Hu C, Komaki RR, Masters GA, Blumenschein GR, Schild SE, Bogart JA, Forster KM, Magliocco AM, Kavadi VS, Narayan S, Iyengar P, Robinson CG, Wynn RB, Koprowski CD, Olson MR, Meng J, Paulus R, Curran WJ Jr, Choy H. Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Mar 1;38(7):706-714. Epub 2019 Dec 16. link to original article link to PMC article PubMed
- Dataset: Project Data Sphere
Maintenance after definitive therapy for inoperable disease
Durvalumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Antonia et al. 2017 (PACIFIC) | 2014-2016 | Phase 3 (E-RT-esc) | Placebo | Superior OS1 (co-primary endpoint) Median OS: 47.5 vs 29.1 mo (HR 0.72, 95% CI 0.59-0.89) |
Awaiting publication (CheckMate 73L) | 2019-2025 | Phase 3 (C) | 1. Ipilimumab & Nivolumab 2. Nivolumab |
TBD if different primary endpoint of PFS |
Awaiting publication (SKYSCRAPER-03) | 2020-2024 | Phase 3 (C) | Atezolizumab & Tiragolumab | TBD if different primary endpoint of PFS |
Awaiting publication (KEYLYNK-012) | 2020-2026 | Phase 3 (C) | 1. Olaparib & Pembrolizumab 2. Pembrolizumab |
TBD if different co-primary endpoints of PFS/OS |
Awaiting publication (BGB-A317-A1217-301) | 2021-2025 | Phase 3 (C) | 1. Ociperlimab & Tislelizumab 2. Tislelizumab |
TBD if different primary endpoint of PFS |
Awaiting publication (PACIFIC-9) | 2022-2026 | Phase 3 (C) | 1. Durvalumab & Monalizumab 2. Durvalumab & Oleclumab |
TBD if different primary endpoint of PFS |
Awaiting publication (PACIFIC-8) | 2022-2027 | Phase 3 (C) | Domvanalimab & Durvalumab | TBD if different primary endpoint of PFS |
1Reported efficacy is based on the 2022 update.
Preceding treatment
- PACIFIC: "Two or more cycles (defined according to local practice) of platinum-based chemoradiotherapy (containing etoposide, vinblastine, vinorelbine, a taxane [paclitaxel or docetaxel], or pemetrexed) concurrently with definitive radiation therapy (5400 to 6600 cGy), in which the mean dose to the lung was less than 2000 cGy, the V20 (the volume of lung parenchyma that received 2000 cGy or more) was less than 35%, or both."
Immunotherapy
- Durvalumab (Imfinzi) 10 mg/kg IV once on day 1
14-day cycle for up to 26 cycles (1 year)
References
- PACIFIC: Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Wadsworth C, Melillo G, Jiang H, Huang Y, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. Epub 2017 Sep 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02125461
- Update: Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, de Wit M, Cho BC, Bourhaba M, Quantin X, Tokito T, Mekhail T, Planchard D, Kim YC, Karapetis CS, Hiret S, Ostoros G, Kubota K, Gray JE, Paz-Ares L, de Castro Carpeño J, Faivre-Finn C, Reck M, Vansteenkiste J, Spigel DR, Wadsworth C, Melillo G, Taboada M, Dennis PA, Özgüroğlu M; PACIFIC Investigators. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018 Dec 13;379(24):2342-2350. Epub 2018 Sep 25. link to original article PubMed
- PRO analysis: Hui R, Özgüroğlu M, Villegas A, Daniel D, Vicente D, Murakami S, Yokoi T, Chiappori A, Lee KH, de Wit M, Cho BC, Gray JE, Rydén A, Viviers L, Poole L, Zhang Y, Dennis PA, Antonia SJ. Patient-reported outcomes with durvalumab after chemoradiotherapy in stage III, unresectable non-small-cell lung cancer (PACIFIC): a randomised, controlled, phase 3 study. Lancet Oncol. 2019 Dec;20(12):1670-1680. Epub 2019 Oct 7. link to original article PubMed
- Update: Gray JE, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Kurata T, Chiappori A, Lee KH, Cho BC, Planchard D, Paz-Ares L, Faivre-Finn C, Vansteenkiste JF, Spigel DR, Wadsworth C, Taboada M, Dennis PA, Özgüroğlu M, Antonia SJ. Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC. J Thorac Oncol. 2020 Feb;15(2):288-293. Epub 2019 Oct 14. link to original article link to PMC article PubMed
- Update: Faivre-Finn C, Vicente D, Kurata T, Planchard D, Paz-Ares L, Vansteenkiste JF, Spigel DR, Garassino MC, Reck M, Senan S, Naidoo J, Rimner A, Wu YL, Gray JE, Özgüroğlu M, Lee KH, Cho BC, Kato T, de Wit M, Newton M, Wang L, Thiyagarajah P, Antonia SJ. Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC-an Update From the PACIFIC Trial. J Thorac Oncol. 2021 May;16(5):860-867. Epub 2021 Jan 19. link to original article PubMed
- Update: Spigel DR, Faivre-Finn C, Gray JE, Vicente D, Planchard D, Paz-Ares L, Vansteenkiste JF, Garassino MC, Hui R, Quantin X, Rimner A, Wu YL, Özgüroğlu M, Lee KH, Kato T, de Wit M, Kurata T, Reck M, Cho BC, Senan S, Naidoo J, Mann H, Newton M, Thiyagarajah P, Antonia SJ. Five-Year Survival Outcomes From the PACIFIC Trial: Durvalumab After Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. J Clin Oncol. 2022 Apr 20;40(12):1301-1311. Epub 2022 Feb 2. link to original article link to PMC article PubMed
- BGB-A317-A1217-301: NCT04866017
- CheckMate 73L: NCT04026412
- KEYLYNK-012: NCT04380636
- PACIFIC-8: NCT05211895
- PACIFIC-9: NCT05221840
- SKYSCRAPER-03: NCT04513925
Sugemalimab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhou et al. 2022 (GEMSTONE-301) | 2018-2020 | Phase 3 (E-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 9 vs 5.8 mo (HR 0.64, 95% CI 0.48-0.85) |
Preceding treatment
- Concurrent or sequential definitive chemoradiotherapy
Immunotherapy
- Sugemalimab (Cejemly) 1200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- GEMSTONE-301: Zhou Q, Chen M, Jiang O, Pan Y, Hu D, Lin Q, Wu G, Cui J, Chang J, Cheng Y, Huang C, Liu A, Yang N, Gong Y, Zhu C, Ma Z, Fang J, Chen G, Zhao J, Shi A, Lin Y, Li G, Liu Y, Wang D, Wu R, Xu X, Shi J, Liu Z, Cui N, Wang J, Wang Q, Zhang R, Yang J, Wu YL. Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):209-219. Epub 2022 Jan 14. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT03728556
Advanced or metastatic disease, first-line
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (SKYSCRAPER-01) | 2020-ongoing | Phase 3 (C) | Atezolizumab & Tiragolumab | TBD if different co-primary endpoints of PFS/OS |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm, in this context.
References
- SKYSCRAPER-01: NCT04294810
Carboplatin & Docetaxel
DCb: Docetaxel & Carboplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fossella et al. 2003 (TAX 326) | 1998-2000 | Phase 3 (E-RT-switch-ic) | 1. Cisplatin & Docetaxel | Not reported |
2. Cisplatin & Vinorelbine | Did not meet primary endpoint of OS | |||
Booton et al. 2006 (BTOG1) | 2001-06 to 2002-11 | Phase 3 (E-switch-ic) | 1a. MIC 1b. MVP |
Did not meet primary endpoint of OS12 OS12: 39% vs 35% |
Groen et al. 2011 (NVALT-4) | 2003-2007 | Phase 3 (C) | DCb & Celecoxib | Did not meet primary endpoint of OS Median OS: 8.2 vs 8.2 mo (HR 1.11, 95% CI 0.83-1.67) |
Lynch et al. 2010 (BMS099) | 2005-01 to 2006-11 | Phase 3 (C) | 1a. CP & Cetuximab 1b. DCb & Cetuximab |
Did not meet primary endpoint of PFS Median PFS: 4.24 vs 4.4 mo (HR 1.11, 95% CI 0.94-1.31) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given second
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycle for varying durations: 4 cycles (BTOG1); 5 cycles (NVALT-4); 6 cycles (BMS099, TAX 326)
References
- TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BMS099: Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00112294
- NVALT-4: Groen HJ, Sietsma H, Vincent A, Hochstenbag MM, van Putten JW, van den Berg A, Dalesio O, Biesma B, Smit HJ, Termeer A, Hiltermann TJ, van den Borne BE, Schramel FM. Randomized, placebo-controlled phase III study of docetaxel plus carboplatin with celecoxib and cyclooxygenase-2 expression as a biomarker for patients with advanced non-small-cell lung cancer: the NVALT-4 study. J Clin Oncol. 2011 Nov 10;29(32):4320-6. Epub 2011 Oct 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NTR1703
Carboplatin & Etoposide (CE)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klastersky et al. 1990 (EORTC 07861) | 1987-1989 | Phase 3 (E-switch-ic) | Cisplatin & Etoposide | Might have inferior ORR |
Chemotherapy
- Carboplatin (Paraplatin) 325 mg/m2 IV over 60 minutes once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 1 to 3
3- to 4-week cycles
References
- EORTC 07861: Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Gemcitabine (GCb)
GC: Gemcitabine & Carboplatin
GCa: Gemcitabine & Carboplatin
GCb: Gemcitabine & Carboplatin
Regimen variant #1, 4/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Helbekkmo et al. 2007 | 2003-10 to 2004-12 | Phase 3 (E-switch-ic) | VCb | Did not meet primary endpoint of OS Median OS: 7.3 vs 6.4 mo |
Note: AUC was calculated using the Chatelut formula.
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for 3 cycles
Regimen variant #2, 5/1000 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Grønberg et al. 2009 | 2005-04 to 2006-07 | Phase 3 (C) | Carboplatin & Pemetrexed | Did not meet primary endpoint of HRQoL |
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 #3, 5/1000 q4wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Danson et al. 2003 | 1997-2001 | Phase 3 (E-switch-ic) | 1a. MIC 1b. MVP |
Did not meet primary endpoint of OS |
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1, 8, 15
28-day cycle for 4 cycles
Regimen variant #4, 5/1200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Zatloukal et al. 2003 | 1999-2001 | Phase 3 (E-switch-ic) | Cisplatin & Gemcitabine | Did not meet primary endpoint of grade 3/4 toxicity | |
Rudd et al. 2005 | 1999-2001 | Phase 3 (E-switch-ic) | MIC | Superior OS (primary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1, given second
- Gemcitabine (Gemzar) 1200 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
21-day cycle for varying durations: 6 cycles (Zatloukal et al. 2003); indefinitely (Rudd et al. 2005)
Regimen variant #5, 5/1250 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Sederholm et al. 2005 | 1998-2001 | Phase 3 (C) | Gemcitabine | Seems to have superior OS | |
Bepler et al. 2013 (MCC-15005) | 2007-2010 | Phase 3 (C) | ERCC1 and RRM1 expression-based chemotherapy | Did not meet primary endpoint of PFS6 PFS6: 56.5% vs 52% |
|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 to 60 minutes once on day 1, given second, at least 4 hours after gemcitabine
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8, given first
21-day cycle for varying durations: 4 to 6 cycles (KEYNOTE-024); 6 cycles (MCC-15005, Sederholm et al. 2005)
Regimen variant #6, 5.5/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Treat et al. 2009 (ALPHA A1-99002L) | 2000-2005 | Phase 3 (E-switch-ic) | CP]] | Did not meet primary endpoint of OS |
Note: this is an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority in this setting.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5.5 IV over 15 to 30 minutes once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for 6 cycles
Regimen variant #7, 6/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kosmidis et al. 2007 | 2000-2004 | Phase 3 (C) | Gemcitabine & Paclitaxel | Did not meet primary endpoint of OS Median OS: 9.97 vs 10.49 mo |
Note: Treatment was continued until maximum response plus 2 cycles, or up to 6 cycles in the case of stable disease.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 60 minutes once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles (see note)
Regimen variant #8, 6/1250 ("GCb6")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ferry et al. 2017 (BTOG2) | 2005-2009 | Phase 3 (E-switch-ic) | 1. GC; GC50 | Seems to have superior OS (primary endpoint) | |
2. GC; GC80 | Non-inferior OS (primary endpoint) | ||||
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for varying durations: 4 cycles (BTOG2); 4 to 6 cycles (KEYNOTE-024)
Regimen variant #9, 300/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Grigorescu et al. 2002 | 1997-2000 | Phase 3 (E-switch-ic) | Cisplatin & Vinblastine | Superior OS |
Chemotherapy
- Carboplatin (Paraplatin) 300 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Grigorescu AC, Draghici IN, Nitipir C, Gutulescu N, Corlan E. Gemcitabine (GEM) and carboplatin (CBDCA) versus cisplatin (CDDP) and vinblastine (VLB) in advanced non-small-cell lung cancer (NSCLC) stages III and IV: a phase III randomised trial. Lung Cancer. 2002 Jul;37(1):9-14. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, Hatton M, Johnson PW, Martin WM, Rankin EM, James LE, Gregory WM, Qian W, Lee SM; London Lung Cancer Group. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol. 2005 Jan 1;23(1):142-53. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR; Swedish Lung Cancer Study Group. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Helbekkmo N, Sundstrøm SH, Aasebø U, Brunsvig PF, von Plessen C, Hjelde HH, Garpestad OK, Bailey A, Bremnes RM; Norwegian Lung Cancer Study Group. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer. 2007 Aug 6;97(3):283-9. Epub 2007 Jun 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ALPHA A1-99002L: Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00054392
- MCC-15005: Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. Epub 2013 May 20. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00499109
- NITRO: Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. link to original article PubMed ACTRN12608000588392
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- BTOG2: Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K; British Thoracic Oncology Group. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00112710
Carboplatin & Gemcitabine (GCb) & Paclitaxel
PCG: Paclitaxel, Carboplatin, Gemcitabine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paccagnella et al. 2006 | 1998-2004 | Phase 2/3 (E-esc) | CP | Seems to have superior OS (co-primary endpoint) Median OS: 10.8 vs 8.3 mo (HR 0.76, 95% CI 0.60-0.97) |
Chemotherapy
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
- Carboplatin (Paraplatin) AUC 6 IV once on day 1, given second
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1 & 8, given third
Supportive therapy
- Dexamethasone (Decadron) 16 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
- Ranitidine (Zantac) (or equivalent) 50 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
21-day cycle for at least 6 cycles
References
- Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Carboplatin & Paclitaxel (CP)
CP: Carboplatin & Paclitaxel
PC: Paclitaxel & Carboplatin
TC: Taxol (Paclitaxel) & Carboplatin
Regimen variant #1, 5/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS | |
Rizvi et al. 2020 (MYSTIC) | 2015-07-21 to 2016-06-08 | Phase 3 (C) | 1. Durvalumab | Might have inferior OS | |
2. Durvalumab & Tremelimumab | Did not meet co-primary endpoints of PFS/OS | ||||
Wu et al. 2020 (KEYNOTE-042 China Extension) | 2016-08-26 to 2018-01-04 | Phase 3 (C) | Pembrolizumab | Inferior OS | |
Sezer et al. 2021 (EMPOWER-Lung 1) | 2017-06-27 to 2020-02-27 | Phase 3 (C) | Cemiplimab | Inferior OS | |
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (C) | Investigator's choice of: 1a. CP & Cemiplimab 1b. TP & Cemiplimab |
Inferior OS |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Biomarker eligibility criteria
- EMPOWER-Lung 1: PD-L1 expressed in at least 50% of tumor cells
- KEYNOTE-042 & KEYNOTE-042 China Extension: PD-L1 tumor proportion score (TPS) of at least 1%
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 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 varying durations: 4 cycles (EMPOWER-Lung 3 part 2); 4 to 6 cycles (all others)
Subsequent treatment
- KEYNOTE-024: Patients with nonsquamous histology could optionally proceed to pemetrexed switch maintenance
Regimen variant #2, 6/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stathopoulos et al. 2004 | 2000-2003 | Phase 3 (C) | Paclitaxel & Vinorelbine | Did not meet co-primary endpoint of ORR ORR: 42.7% vs 37.85% Did not meet co-primary endpoint of OS Median OS: 11 vs 10 mo |
Lynch et al. 2012 (CA184-041NSCLC) | 2008-2009 | Randomized Phase 2 (C) | 1. CP & Ipilimumab; phased ipilimumab | Seems to have inferior irPFS |
2. CP & Ipilimumab; concurrent ipilimumab | Did not meet primary endpoint of irPFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
Supportive therapy
- Corticosteroids could be used as premedication for paclitaxel infusion.
21-day cycle for up to 6 cycles
Regimen variant #3, 6/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Rosell et al. 2002 | 1996-04 to 1997-07 | Phase 3 (E-switch-ic) | Cisplatin & Paclitaxel | Seems to have inferior OS | |
Socinski et al. 2002 | 1998-2000 | Phase 3 (E-de-esc) | CP; indefinite | Did not meet primary endpoint of OS | Did not meet primary endpoint of QoL |
Kosmidis et al. 2002 | 1998-2000 | Phase 3 (E-switch-ic) | Gemcitabine & Paclitaxel | Did not meet primary endpoint of OS | |
Johnson et al. 2004 | Not reported | Randomized Phase 2 (C) | PacCBev | Seems to have inferior TTP | |
Paccagnella et al. 2006 | 1998-2004 | Phase 2/3 (C) | PCG | Seems to have inferior OS | |
Leighl et al. 2005 (NCIC-CTG BR.18) | 2000-2002 | Phase 3 (C) | CP & Rebimastat | Did not meet primary endpoint of OS Median OS: 9.2 vs 8.6 mo (HR 0.92, 95% CI 0.78-1.08) |
Less toxic |
Ohe et al. 2006 (FACS) | 2000-2002 | Phase 3 (E-switch-ic) | 1. Cisplatin & Gemcitabine | Inconclusive whether non-inferior OS (primary endpoint) | |
2. Cisplatin & Irinotecan | Inconclusive whether non-inferior OS (primary endpoint) | ||||
3. Cisplatin & Vinorelbine | Inconclusive whether non-inferior OS (primary endpoint) | ||||
Herbst et al. 2005 (TRIBUTE) | 2001-07-18 to 2002-08-19 | Phase 3 (C) | CP & Erlotinib | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.6 mo (HR 1.01, 95% CI 0.86-1.16) |
|
Schuette et al. 2006 | Not reported | Phase 3 (C) | CP; weekly | Seems to have non-inferior ORR (primary endpoint) | Mixed toxicity |
Blumenschein et al. 2008 (SPIRIT II) | 2002 to not reported | Phase 3 (C) | CP & Bexarotene | Did not meet primary endpoint of OS Median OS: 9.2 vs 8.5 mo |
|
Hirsh et al. 2011 (A8501001) | 2005-2007 | Phase 3 (C) | CP & Agatolimod | Did not meet primary endpoint of OS Median OS: 9.8 vs 10 mo (HR 1.05, 95% CI 0.89-1.23) |
|
Scagliotti et al. 2010 (ESCAPE) | 2006-02 to 2007-05 | Phase 3 (C) | CP & Sorafenib | Did not meet primary endpoint of OS Median OS: 10.6 vs 10.7 mo (HR 0.87, 95% CI 0.71-1.06) |
|
Okamoto et al. 2010 (LETS) | 2006-2008 | Phase 3 (C) | Carboplatin & S-1 | Non-inferior OS (primary endpoint) | |
Socinski et al. 2012 (CA031) | 2007-2009 | Phase 3 (C) | Carboplatin & nab-Paclitaxel | Inferior ORR | |
Langer et al. 2014 (A4021016) | 2008-04 to 2009-09 | Phase 3 (C) | CP & Figitumumab | Might have superior OS (primary endpoint) Median OS: 9.8 vs 8.6 mo (HR 0.85, 95% CI 0.71-1.01) |
|
Lara et al. 2011 (ATTRACT-1) | 2008-04 to 2009-10 | Phase 3 (C) | CP & Vadimezan | Did not meet primary endpoint of OS Median OS: 12.7 vs 13.4 mo (HR 0.99, 95% CI 0.84-1.18) |
|
Laurie et al. 2013 (NCIC-CTG BR.29) | 2008-2011 | Phase 3 (C) | CP & Cediranib | Did not meet primary endpoint of OS Median OS: 12.1 vs 12.2 mo (HR 1.06, 95% CI 0.77-1.45) |
Less toxic |
Herbst et al. 2017 (SWOG S0819) | 2009-2014 | Phase 3 (C) | 1a. CP & Cetuximab 1b. CP, Bevacizumab, Cetuximab |
Might have inferior OS (co-primary endpoint) Median OS: 10.9 vs 9.2 mo (HR 1.08, 95% CI 0.96-1.19) |
|
Ramalingam et al. 2016 (M10-898) | 2012-2013 | Randomized Phase 2 (C) | CP & Veliparib | Did not meet primary endpoint of PFS Median PFS: 4.2 vs 5.8 mo (HR 1.39, 95% CI 0.87-2.22) |
|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Phase 3 (C) | Pembrolizumab | Inferior OS | |
Rizvi et al. 2020 (MYSTIC) | 2015-07-21 to 2016-06-08 | Phase 3 (C) | 1. Durvalumab | Might have inferior OS | |
2. Durvalumab & Tremelimumab | Did not meet co-primary endpoints of PFS/OS | ||||
Wu et al. 2020 (KEYNOTE-042 China Extension) | 2016-08-26 to 2018-01-04 | Phase 3 (C) | Pembrolizumab | Inferior OS | |
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (C) | Investigator's choice of: 1a. CP & Cemiplimab 1b. TP & Cemiplimab |
Inferior OS |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Biomarker eligibility criteria
- KEYNOTE-042 & KEYNOTE-042 China Extension: PD-L1 tumor proportion score (TPS) of at least 1%
- SWOG S0819: EGFR FISH positive
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 30 minutes once on day 1, given second, 60 minutes after completion of paclitaxel
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron) (varies per trial):
- 20 mg IV once on day 1, given 30 minutes prior to paclitaxel
- 20 mg PO once on day -1, given 12 hours prior to paclitaxel, then 20 mg IV once on day 1, given 30 minutes prior to paclitaxel
- Diphenhydramine (Benadryl) 50 mg IV once on day 1, given 30 minutes prior to paclitaxel
- Ondansetron (Zofran) 16 mg IV once on day 1, given 15 minutes prior to chemotherapy, then 8 mg PO twice per day on days 1 to 3
- One of the following H2 blockers:
- Ranitidine (Zantac) 50 mg IV once on day 1, given 30 minutes prior to paclitaxel
- Cimetidine (Tagamet) 300 mg IV once on day 1, given 30 minutes prior to paclitaxel
21-day cycle for varying durations: 3 or more cycles (FACS); 4 cycles (EMPOWER-Lung 3 part 2, Socinski et al. 2002); 4 or more cycles (SPIRIT II); 4 to 6 cycles (KEYNOTE-024, KEYNOTE-042, KEYNOTE-042 China Extension, MYSTIC, NCIC-CTG BR.29); 6 cycles (A4021016, A8501001, ATTRACT-1, ESCAPE, Johnson et al. 2004, LETS, M10-898, Schuette et al. 2006, SWOG S0819, TRIBUTE); 6 or more cycles (CA031, Kosmidis et al. 2002, Paccagnella et al. 2006); 8 cycles (NCIC-CTG BR.18); 10 cycles (Rosell et al. 2002)
Subsequent treatment
- Socinski et al. 2002, upon progression: Second-line Paclitaxel
- KEYNOTE-024, patients with nonsquamous histology: optional pemetrexed switch maintenance
Regimen variant #4, 6/225
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kelly et al. 2001 (SWOG 9509) | 1996-1998 | Phase 3 (E-switch-ic) | Cisplatin & Vinorelbine | Did not meet primary endpoint of OS |
Schiller et al. 2002 (ECOG E1594) | 1996-1999 | Phase 3 (E-switch-ic) | 1. Cisplatin & Docetaxel | Did not meet primary endpoint of OS |
2. Cisplatin & Gemcitabine | Did not meet primary endpoint of OS | |||
3. Cisplatin & Paclitaxel | Did not meet primary endpoint of OS | |||
Lilenbaum et al. 2005 (CALGB 9730) | 1997-2000 | Phase 3 (E-esc) | Paclitaxel | Did not meet primary endpoint of OS Median OS: 8.8 vs 6.7 mo (HR 0.91, 95% CI 0.77-1.17) |
Herbst et al. 2004 (INTACT 2) | 2000-05 to 2001-04 | Phase 3 (C) | 1. CP & Gefitinib; 250 mg/d 2. CP & Gefitinib; 500 mg/d |
Did not meet primary endpoint of OS |
Williamson et al. 2005 (SWOG S0003) | 2000-2002 | Phase 3 (C) | CP & Tirapazamine | Did not meet primary endpoint of OS Median OS: 9 vs 9 mo |
Belani et al. 2008 (BMS TAX/MEN.12) | 2000-2004 | Phase 3 (C) | CP; weekly paclitaxel | Did not meet primary endpoint of OS Median OS: 42.9 vs 38.6 wk |
Treat et al. 2009 (ALPHA A1-99002L) | 2000-2005 | Phase 3 (C) | 1. Carboplatin & Gemcitabine 2. Gemcitabine & Paclitaxel |
Did not meet primary endpoint of OS |
Kubota et al. 2008 (JMTO LC00-03) | 2001-2005 | Phase 3 (C) | GVb-D | Did not meet primary endpoint of OS Median OS: 14.1 vs 13.6 mo |
Weissman et al. 2011 (SR96669) | 2004-03-04 to 2005-04-15 | Phase 3 (C) | GemOx | Did not meet primary endpoint of PFS Median PFS: 4.7 vs 4.4 mo |
Lynch et al. 2010 (BMS099) | 2005-01 to 2006-11 | Phase 3 (C) | 1a. CP & Cetuximab 1b. DCb & Cetuximab |
Did not meet primary endpoint of PFS Median PFS: 4.24 vs 4.4 mo (HR 1.11, 95% CI 0.94-1.31) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 30 minutes once on day 1, given second
- Paclitaxel (Taxol) 225 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for varying durations: 4 cycles (BMS TAX/MEN.12); 6 cycles (ALPHA A1-99002L, BMS099, CALGB 9730, INTACT 2, JMTO LC00-03, SR96669, SWOG S0003); 10 cycles (SWOG 9509); indefinitely (ECOG E1594)
Subsequent treatment
- BMS TAX/MEN.12: Paclitaxel maintenance
References
- SWOG 9509: Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Socinski MA, Schell MJ, Peterman A, Bakri K, Yates S, Gitten R, Unger P, Lee J, Lee JH, Tynan M, Moore M, Kies MS. Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol. 2002 Mar 1;20(5):1335-43. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Kosmidis P, Mylonakis N, Nicolaides C, Kalophonos C, Samantas E, Boukovinas J, Fountzilas G, Skarlos D, Economopoulos T, Tsavdaridis D, Papakostas P, Bacoyiannis C, Dimopoulos M. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2002 Sep 1;20(17):3578-85. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- INTACT 2: Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, Wolf MK, Krebs AD, Averbuch SD, Ochs JS, Grous J, Fandi A, Johnson DH. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. J Clin Oncol. 2004 Mar 1;22(5):785-94. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Stathopoulos GP, Veslemes M, Georgatou N, Antoniou D, Giamboudakis P, Katis K, Tsavdaridis D, Rigatos SK, Dimitroulis I, Bastani S, Loukides S, Vergos K, Marossis K, Grigoratou T, Kalatzi E, Charalambatou M, Paspalli A, Michalopoulou P, Stoka M, Gerogianni A. Front-line paclitaxel-vinorelbine versus paclitaxel-carboplatin in patients with advanced non-small-cell lung cancer: a randomized phase III trial. Ann Oncol. 2004 Jul;15(7):1048-55. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- CALGB 9730: Lilenbaum RC, Herndon JE 2nd, List MA, Desch C, Watson DM, Miller AA, Graziano SL, Perry MC, Saville W, Chahinian P, Weeks JC, Holland JC, Green MR. Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the Cancer and Leukemia Group B (study 9730). J Clin Oncol. 2005 Jan 1;23(1):190-6. link to original articledosing details in manuscript have been reviewed by our editors PubMed NCT00003117
- NCIC-CTG BR.18: Leighl NB, Paz-Ares L, Douillard JY, Peschel C, Arnold A, Depierre A, Santoro A, Betticher DC, Gatzemeier U, Jassem J, Crawford J, Tu D, Bezjak A, Humphrey JS, Voi M, Galbraith S, Hann K, Seymour L, Shepherd FA. Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00006229
- TRIBUTE: Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA; TRIBUTE Investigator Group. TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5892-9. Epub 2005 Jul 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00047736
- SWOG S0003: Williamson SK, Crowley JJ, Lara PN Jr, McCoy J, Lau DH, Tucker RW, Mills GM, Gandara DR; SWOG. Phase III trial of paclitaxel plus carboplatin with or without tirapazamine in advanced non-small-cell lung cancer: Southwest Oncology Group Trial S0003. J Clin Oncol. 2005 Dec 20;23(36):9097-104. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00006484
- Schuette W, Blankenburg T, Guschall W, Dittrich I, Schroeder M, Schweisfurth H, Chemaissani A, Schumann C, Dickgreber N, Appel T, Ukena D. Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Clin Lung Cancer. 2006 Mar;7(5):338-43. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Paccagnella A, Oniga F, Bearz A, Favaretto A, Clerici M, Barbieri F, Riccardi A, Chella A, Tirelli U, Ceresoli G, Tumolo S, Ridolfi R, Biason R, Nicoletto MO, Belloni P, Veglia F, Ghi MG. Adding gemcitabine to paclitaxel/carboplatin combination increases survival in advanced non-small-cell lung cancer: results of a phase II-III study. J Clin Oncol. 2006 Feb 1;24(4):681-7. Erratum in: J Clin Oncol. 2006 May 10;24(14):2220. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- BMS TAX/MEN.12: Belani CP, Ramalingam S, Perry MC, LaRocca RV, Rinaldi D, Gable PS, Tester WJ. Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer. J Clin Oncol. 2008 Jan 20;26(3):468-73. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00035152
- SPIRIT II: Blumenschein GR Jr, Khuri FR, von Pawel J, Gatzemeier U, Miller WH Jr, Jotte RM, Le Treut J, Sun SL, Zhang JK, Dziewanowska ZE, Negro-Vilar A. Phase III trial comparing carboplatin, paclitaxel, and bexarotene with carboplatin and paclitaxel in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT II. J Clin Oncol. 2008 Apr 10;26(11):1879-85. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00050960
- JMTO LC00-03: Kubota K, Kawahara M, Ogawara M, Nishiwaki Y, Komuta K, Minato K, Fujita Y, Teramukai S, Fukushima M, Furuse K; Japan Multi-National Trial Organisation. Vinorelbine plus gemcitabine followed by docetaxel versus carboplatin plus paclitaxel in patients with advanced non-small-cell lung cancer: a randomised, open-label, phase III study. Lancet Oncol. 2008 Dec;9(12):1135-42. Epub 2008 Nov 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00079287
- ALPHA A1-99002L: Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00054392
- BMS099: Lynch TJ, Patel T, Dreisbach L, McCleod M, Heim WJ, Hermann RC, Paschold E, Iannotti NO, Dakhil S, Gorton S, Pautret V, Weber MR, Woytowitz D. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non-small-cell lung cancer: results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010 Feb 20;28(6):911-7. Epub 2010 Jan 25. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00112294
- ESCAPE: Scagliotti G, Novello S, von Pawel J, Reck M, Rodrigues Pereira J, Thomas M, Abrão Miziara JE, Balint B, De Marinis F, Keller A, Arén O, Csollak M, Albert I, Barrios CH, Grossi F, Krzakowski M, Cupit L, Cihon F, Dimatteo S, Hanna N. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010 Apr 10;28(11):1835-42. Epub 2010 Mar 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00300885
- Dataset: Project Data Sphere
- LETS: Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K; West Japan Oncology Group. Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a West Japan Oncology Group study. J Clin Oncol. 2010 Dec 20;28(36):5240-6. Epub 2010 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000503
- SR96669: Weissman CH, Reynolds CH, Neubauer MA, Pritchard S, Kobina S, Asmar L. A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2011 Feb;6(2):358-64. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00087802
- A8501001: Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE, Szczesna A, Reiterer P, Saleh M, Arrieta O, Bajetta E, Webb RT, Raats J, Benner RJ, Fowst C, Meech SJ, Readett D, Schiller JH. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2011 Jul 1;29(19):2667-74. Epub 2011 May 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00254891
- ATTRACT-1: Lara PN Jr, Douillard JY, Nakagawa K, von Pawel J, McKeage MJ, Albert I, Losonczy G, Reck M, Heo DS, Fan X, Fandi A, Scagliotti G. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol. 2011 Aug 1;29(22):2965-71. Epub 2011 Jun 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00662597
- CA184-041NSCLC: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00527735
- CA031: Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00540514
- Dataset: Project Data Sphere
- NCIC-CTG BR.29: Laurie SA, Solomon BJ, Seymour L, Ellis PM, Goss GD, Shepherd FA, Boyer MJ, Arnold AM, Clingan P, Laberge F, Fenton D, Hirsh V, Zukin M, Stockler MR, Lee CW, Chen EX, Montenegro A, Ding K, Bradbury PA. Randomised, double-blind trial of carboplatin and paclitaxel with daily oral cediranib or placebo in patients with advanced non-small cell lung cancer: NCIC Clinical Trials Group study BR29. Eur J Cancer. 2014 Mar;50(4):706-12. Epub 2013 Dec 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00795340
- A4021016: Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2. link to original article link to PMC article PubMed NCT00596830
- NITRO: Davidson A, Veillard AS, Tognela A, Chan MM, Hughes BG, Boyer M, Briscoe K, Begbie S, Abdi E, Crombie C, Long J, Boyce A, Lewis CR, Varma S, Broad A, Muljadi N, Chinchen S, Espinoza D, Coskinas X, Pavlakis N, Millward M, Stockler MR; Australasian Lung cancer Trials Group (ALTG); Australasian Lung cancer Trials Group ALTG. A phase III randomized trial of adding topical nitroglycerin to first-line chemotherapy for advanced nonsmall-cell lung cancer: the Australasian lung cancer trials group NITRO trial. Ann Oncol. 2015 Nov;26(11):2280-6. Epub 2015 Sep 7. link to original article PubMed ACTRN12608000588392
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- M10-898: Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E, Urban L, Orlov S, Barlesi F, Kio E, Keiholz U, Qin Q, Qian J, Nickner C, Dziubinski J, Xiong H, Ansell P, McKee M, Giranda V, Gorbunova V. Randomized, placebo-controlled, phase II study of veliparib in combination with carboplatin and paclitaxel for advanced/metastatic non-small cell lung cancer. Clin Cancer Res. 2017 Apr 15;23(8):1937-1944. Epub 2016 Oct 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01560104
- SWOG S0819: Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00946712
- MYSTIC: Rizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):661-674. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT02453282
- KEYNOTE-042 China Extension: Wu YL, Zhang L, Fan Y, Zhou J, Zhang L, Zhou Q, Li W, Hu C, Chen G, Zhang X, Zhou C, Dang T, Sadowski S, Kush DA, Zhou Y, Li B, Mok T. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021 May 1;148(9):2313-2320. Epub 2020 Dec 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03850444
- EMPOWER-Lung 1: Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03088540
- Update: Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Sep;24(9):989-1001. Epub 2023 Aug 14. link to original article PubMed
- EMPOWER-Lung 3 part 2: Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Li S, McGuire K, Kaul M, Paccaly A, Quek RGW, Gao B, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Gullo G, Rietschel P. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022 Nov;28(11):2374-2380. Epub 2022 Aug 25. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03409614
- PRO analysis: Makharadze T, Quek RGW, Melkadze T, Gogishvili M, Ivanescu C, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Konidaris G, Rietschel P, Gullo G. Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3. Cancer. 2023 Jul 15;129(14):2256-2265. Epub 2023 May 8. link to original article PubMed
- ARC-10: NCT04736173
Carboplatin & nab-Paclitaxel
Regimen variant #1, AUC 5
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (C) | 1. CnP & Durvalumab | Might have inferior OS |
2. CnP, Durvalumab, Tremelimumab | Inferior OS |
Note: POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 to 6 cycles
Regimen variant #2, AUC 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Socinski et al. 2012 (CA031) | 2007-2009 | Phase 3 (E-RT-switch-ic) | Carboplatin & Paclitaxel | Superior ORR (primary endpoint) ORR: 33% vs 25% (RR ratio 1.31, 95% CI 1.08-1.59) |
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (C) | 1. CnP & Durvalumab | Might have inferior OS |
2. CnP, Durvalumab, Tremelimumab | Inferior OS |
Note: In CA031, treatment could continue past 6 cycles at physician's discretion if there was no progressive disease or unacceptable toxicity. POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 (Calvert formula) IV once on day 1, given second
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, given first
21-day cycle for varying durations: 4 to 6 cycles (POSEIDON); 6 or more cycles (CA031)
References
- CA031: Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00540514
- Dataset: Project Data Sphere
- POSEIDON: Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. Epub 2022 Nov 3. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03164616
Carboplatin, nab-Paclitaxel, Durvalumab
Regimen variant #1, AUC 5
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (E-esc) | 1. CnP | Might have superior OS (co-primary endpoint) Median OS: 13.3 vs 11.7 mo (HR 0.86, 95% CI 0.72-1.02) Superior PFS (co-primary endpoint) Median PFS: 5.5 vs 4.8 mo (HR 0.74, 95% CI 0.62-0.89) |
2. CnP, Durvalumab, Tremelimumab | Not reported |
Note: POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV over 60 minutes once on day 1
- Cycle 5 onwards: 1500 mg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 28-day cycles
Regimen variant #2, AUC 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (E-esc) | 1. CnP | Might have superior OS (co-primary endpoint) Median OS: 13.3 vs 11.7 mo (HR 0.86, 95% CI 0.72-1.02) Superior PFS (co-primary endpoint) Median PFS: 5.5 vs 4.8 mo (HR 0.74, 95% CI 0.62-0.89) |
2. CnP, Durvalumab, Tremelimumab | Not reported |
Note: POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 6 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV over 60 minutes once on day 1
- Cycle 5 onwards: 1500 mg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- POSEIDON: Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. Epub 2022 Nov 3. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03164616
Carboplatin, nab-Paclitaxel, Durvalumab, Tremelimumab
Regimen variant #1, AUC 5
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (E-RT-esc) | 1. CnP | Superior OS (co-primary endpoint) Median OS: 14 vs 11.7 mo (HR 0.77, 95% CI 0.65-0.92) Superior PFS (co-primary endpoint) Median PFS: 6.2 vs 4.8 mo (HR 0.72, 95% CI 0.60-0.86) |
2. CnP & Durvalumab | Not reported |
Note: POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV over 60 minutes once on day 1
- Cycle 5 onwards: 1500 mg IV over 60 minutes once on day 1
- Tremelimumab (Imjudo) as follows:
- Cycles 1 to 4, 6: 75 mg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 28-day cycles
Regimen variant #2, AUC 6
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2022 (POSEIDON) | 2017-06-27 to 2018-09-19 | Phase 3 (E-RT-esc) | 1. CnP | Superior OS (co-primary endpoint) Median OS: 14 vs 11.7 mo (HR 0.77, 95% CI 0.65-0.92) Superior PFS (co-primary endpoint) Median PFS: 6.2 vs 4.8 mo (HR 0.72, 95% CI 0.60-0.86) |
2. CnP & Durvalumab | Not reported |
Note: POSEIDON had additional treatment options for histology-specific subgroups; please see the respective pages for more details.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 6 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
- Cycles 1 to 4: 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Durvalumab (Imfinzi) as follows:
- Cycles 1 to 4: 1500 mg IV over 60 minutes once on day 1
- Cycle 5 onwards: 1500 mg IV over 60 minutes once on day 1
- Tremelimumab (Imjudo) as follows:
- Cycles 1 to 4, 6: 75 mg IV over 60 minutes once on day 1
21-day cycle for 4 cycles, then 28-day cycles
References
- POSEIDON: Johnson ML, Cho BC, Luft A, Alatorre-Alexander J, Geater SL, Laktionov K, Kim SW, Ursol G, Hussein M, Lim FL, Yang CT, Araujo LH, Saito H, Reinmuth N, Shi X, Poole L, Peters S, Garon EB, Mok T; POSEIDON investigators. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. Epub 2022 Nov 3. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03164616
Carboplatin & Paclitaxel (CP) & Bevacizumab
PacCBev: Paclitaxel, Carboplatin, Bevacizumab
B+CP: Bevacizumab, Carboplatin, Paclitaxel
BCP: Bevacizumab, Carboplatin, Paclitaxel
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Johnson et al. 2004 | Not reported | Randomized Phase 2 (E-esc) | Carboplatin & Paclitaxel | Seems to have superior TTP (co-primary endpoint) |
Herbst et al. 2017 (SWOG S0819) | 2009-2014 | Phase 3 (C) | 1a. CP & Cetuximab 1b. CP, Bevacizumab, Cetuximab |
Might have inferior OS (co-primary endpoint) Median OS: 10.9 vs 9.2 mo (HR 1.08, 95% CI 0.96-1.19) |
Biomarker eligibility criteria
- SWOG S0819: EGFR FISH positive
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV over 15 to 30 minutes once on day 1, given second, starting 60 minutes after the completion of paclitaxel
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1, given first
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1, given third, starting 60 minutes after the completion of carboplatin
- Infusion time per Johnson, et al. 2004 was over 90 minutes for cycle 1; if tolerated, given over 30 to 60 minutes for cycles 2 and later
21-day cycle for up to 6 cycles
References
- Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SWOG S0819: Herbst RS, Redman MW, Kim ES, Semrad TJ, Bazhenova L, Masters G, Oettel K, Guaglianone P, Reynolds C, Karnad A, Arnold SM, Varella-Garcia M, Moon J, Mack PC, Blanke CD, Hirsch FR, Kelly K, Gandara DR. Cetuximab plus carboplatin and paclitaxel with or without bevacizumab versus carboplatin and paclitaxel with or without bevacizumab in advanced NSCLC (SWOG S0819): a randomised, phase 3 study. Lancet Oncol. 2018 Jan;19(1):101-114. Epub 2017 Nov 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00946712
Carboplatin & Paclitaxel (CP) & Cemiplimab
Regimen variant #1, 5/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (E-RT-esc) | Investigator's choice of: 1a. CP 1b. Cisplatin & Paclitaxel |
Superior OS (primary endpoint) Median OS: 21.9 vs 13 mo (HR 0.71, 95% CI 0.53-0.93) |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 5 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 200 mg/m2 IV once on day 1
Immunotherapy
- Cemiplimab (Libtayo) 350 mg IV once on day 1
21-day cycle for up to 36 cycles (2 years)
Regimen variant #2, 6/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (E-RT-esc) | Investigator's choice of: 1a. CP 1b. Cisplatin & Paclitaxel |
Superior OS (primary endpoint) Median OS: 21.9 vs 13 mo (HR 0.71, 95% CI 0.53-0.93) |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 4: AUC 6 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 200 mg/m2 IV once on day 1
Immunotherapy
- Cemiplimab (Libtayo) 350 mg IV once on day 1
21-day cycle for up to 36 cycles (2 years)
References
- EMPOWER-Lung 3 part 2: Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Li S, McGuire K, Kaul M, Paccaly A, Quek RGW, Gao B, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Gullo G, Rietschel P. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022 Nov;28(11):2374-2380. Epub 2022 Aug 25. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03409614
- PRO analysis: Makharadze T, Quek RGW, Melkadze T, Gogishvili M, Ivanescu C, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Konidaris G, Rietschel P, Gullo G. Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3. Cancer. 2023 Jul 15;129(14):2256-2265. Epub 2023 May 8. link to original article PubMed
Carboplatin & Paclitaxel (CP) & Ipilimumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lynch et al. 2012 (CA184-041NSCLC) | 2008-2009 | Randomized Phase 2 (E-esc) | 1. Carboplatin & Paclitaxel | Seems to have superior irPFS (primary endpoint) |
2. CP & Ipilimumab; concurrent Ipilimumab | Not reported |
Note: this is the "phased" approach to this regimen.
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Cycles 3 to 6: 10 mg/kg IV once on day 1
Supportive therapy
- Corticosteroids could be used as premedication for paclitaxel infusion or for toxicity management.
21-day cycle for up to 6 cycles
Subsequent treatment
- Maintenance ipilimumab
References
- CA184-041NSCLC: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00527735
Carboplatin & Pemetrexed
CP: Carboplatin & Pemetrexed
Carbo-Pem: Carboplatin & Pemetrexed
Example orders
Regimen variant #1, 5/500
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Grønberg et al. 2009 | 2005-04 to 2006-07 | Phase 3 (E-switch-ic) | Carboplatin & Gemcitabine | Did not meet primary endpoint of HRQoL | |
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
Wu et al. 2020 (KEYNOTE-042 China Extension) | 2016-08-26 to 2018-01-04 | Phase 3 (C) | Pembrolizumab | Inferior OS |
Biomarker eligibility criteria
- KEYNOTE-042 China Extension: PD-L1 TPS of at least 1%
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 varying durations: 4 cycles (Grønberg et al. 2009); 4 to 6 cycles (KEYNOTE-024, KEYNOTE-042 China Extension)
Subsequent treatment
- KEYNOTE-024: Optional pemetrexed maintenance
- KEYNOTE-042 China Extension, patients with nonsquamous histology: Optional pemetrexed maintenance
Regimen variant #2, 6/500
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity | |
---|---|---|---|---|---|---|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL | |
Wu et al. 2020 (KEYNOTE-042 China Extension) | 2016-08-26 to 2018-01-04 | Phase 3 (C) | Pembrolizumab | Inferior OS |
Biomarker eligibility criteria
- KEYNOTE-042 China Extension: PD-L1 TPS of at least 1%
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Supportive therapy
- Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose prior to pemetrexed
- Folic acid (Folate) 1 mg PO once per day
21-day cycle for 4 to 6 cycles
Subsequent treatment
- KEYNOTE-024: Optional pemetrexed maintenance
- KEYNOTE-042 China Extension, patients with nonsquamous histology: Optional pemetrexed maintenance
References
- Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S; Norwegian Lung Cancer Study Group. Phase III study by the Norwegian Lung Cancer Study Group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- KEYNOTE-042 China Extension: Wu YL, Zhang L, Fan Y, Zhou J, Zhang L, Zhou Q, Li W, Hu C, Chen G, Zhang X, Zhou C, Dang T, Sadowski S, Kush DA, Zhou Y, Li B, Mok T. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021 May 1;148(9):2313-2320. Epub 2020 Dec 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03850444
Carboplatin & S-1
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Okamoto et al. 2010 (LETS) | 2006-2008 | Phase 3 (E-switch-ic) | CP | Non-inferior OS (primary endpoint) Median OS: 15.2 vs 13.3 mo (HR 0.93, 99.2% CI 0.67-1.28) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Tegafur, gimeracil, oteracil (S-1) 40 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 6 cycles
References
- LETS: Okamoto I, Yoshioka H, Morita S, Ando M, Takeda K, Seto T, Yamamoto N, Saka H, Asami K, Hirashima T, Kudoh S, Satouchi M, Ikeda N, Iwamoto Y, Sawa T, Miyazaki M, Tamura K, Kurata T, Fukuoka M, Nakagawa K; West Japan Oncology Group. Phase III trial comparing oral S-1 plus carboplatin with paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small-cell lung cancer: results of a West Japan Oncology Group study. J Clin Oncol. 2010 Dec 20;28(36):5240-6. Epub 2010 Nov 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000503
Carboplatin & Vinorelbine
VC: Vinorelbine & Carboplatin
Regimen variant #1, 4/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Helbekkmo et al. 2007 | 2003-10 to 2004-12 | Phase 3 (E-switch-ic) | GCb | Did not meet primary endpoint of OS Median OS: 6.4 vs 7.3 mo |
Note: The carboplatin dose was calculated by the Chatelut formula.
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 IV over 60 minutes once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV over 10 minutes once per day on days 1 & 8
21-day cycle for 3 cycles
Regimen variant #2, 5/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tan et al. 2005 (GLOB 2) | 2000-2002 | Phase 3 (C) | Gemcitabine & Vinorelbine | Did not meet primary endpoint of ORR ORR: 20.8% vs 28% |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #3, 5/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fløtten et al. 2012 | 2007-2009 | Phase 3 (C) | Gemcitabine & Vinorelbine | Did not meet primary endpoint of OS Median OS: 7 vs 6.3 mo (HR 0.98, 95% CI 0.81-1.18) |
Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Vinorelbine (Navelbine) 60 mg/m2 PO once per day on days 1 & 8
21-day cycle for 3 cycles
References
- GLOB 2: Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Helbekkmo N, Sundstrøm SH, Aasebø U, Brunsvig PF, von Plessen C, Hjelde HH, Garpestad OK, Bailey A, Bremnes RM; Norwegian Lung Cancer Study Group. Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer. 2007 Aug 6;97(3):283-9. Epub 2007 Jun 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00737867
Cemiplimab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sezer et al. 2021 (EMPOWER-Lung 1) | 2017-06-27 to 2020-02-27 | Phase 3 (E-RT-switch-ooc) | 1a. Carboplatin & Gemcitabine 1b. Carboplatin & Paclitaxel 1c. Carboplatin & Pemetrexed 1d. Cisplatin & Gemcitabine 1e. Cisplatin & Paclitaxel 1f. Cisplatin & Pemetrexed |
Superior OS1 (co-primary endpoint) Median OS: 26.1 vs 13.3 mo (HR 0.57, 95% CI 0.46-0.71) |
1Reported efficacy is based on the 2023 update.
Note: some of the comparator platinum doublets appear to be histology-specific, but this is not specified in the manuscript or protocol. We have reached out to the authors for clarification. Per Sanofi, "it was strongly recommended that patients with squamous NSCLC do not receive pemetrexed-containing regimens"; otherwise, no histology-specific guidance was provided to the investigator.
Biomarker eligibility criteria
- PD-L1 expressed in at least 50% of tumor cells
Immunotherapy
- Cemiplimab (Libtayo) 350 mg IV over 30 minutes once on day 1
21-day cycle for up to 36 cycles (2 years)
References
- EMPOWER-Lung 1: Sezer A, Kilickap S, Gümüş M, Bondarenko I, Özgüroğlu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03088540
- Update: Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Sep;24(9):989-1001. Epub 2023 Aug 14. link to original article PubMed
Cisplatin & Docetaxel (DC)
DC: Docetaxel & Cisplatin
DP: Docetaxel & Platinol (Cisplatin)
Doc-Cis: Docetaxel & Cisplatin
Regimen variant #1, 50/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Berghmans et al. 2013 (ELCWP-01041) | 2003-2009 | Phase 3 (C) | 1. GIP 2. IG |
Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
Regimen variant #2, 75/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schiller et al. 2002 (ECOG E1594) | 1996-1999 | Phase 3 (E-switch-ic) | 1. Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
2. Cisplatin & Gemcitabine | Did not meet primary endpoint of OS | |||
3. Cisplatin & Paclitaxel | Did not meet primary endpoint of OS | |||
Fossella et al. 2003 (TAX 326) | 1998-2000 | Phase 3 (E-RT-switch-ic) | 1. Carboplatin & Docetaxel | Not reported |
2. Cisplatin & Vinorelbine | Seems to have superior OS (primary endpoint) | |||
Cobo et al. 2007 | 2001-2005 | Phase 3 (C) | ERCC1 mRNA-guided therapy | Seems to have inferior ORR |
Tan et al. 2009 (GLOB3) | 2004-2006 | Phase 3 (C) | Cisplatin & Vinorelbine | Did not meet primary endpoint of TTF Median TTF: 4.1 vs 3.2 mo |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1, given second
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycle for varying durations: 6 cycles (GLOB3, TAX326); indefinitely (Cobo et al. 2007, ECOG E1594)
Regimen variant #3, 80/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kubota et al. 2004 | 1998-2000 | Phase 3 (E-switch-ic) | Cisplatin & Vindesine | Seems to have superior OS (primary endpoint) Median OS: 11.3 vs 9.6 mo |
Takeda et al. 2009 (WJTOG0203) | 2003-2005 | Phase 3 (C) | Platinum doublet x 3, then Gefitinib | Might have inferior OS (primary endpoint) Median OS: 12.9 vs 13.7 mo (HR 1.16, 95% CI 0.97-1.39) |
Kubota et al. 2015 (TCOG0701 CATS) | 2007-04 to 2008-12 | Phase 3 (C) | Cisplatin & S-1 | Non-inferior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 90 to 120 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 of varying durations: 2 or more cycles (Kubota et al. 2004); 3 to 6 cycles (TCOG0701 CATS); 6 cycles (WJTOG0203)
Regimen variant #4, 80/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Georgoulias et al. 2001 | 1997-1999 | Phase 3 (C) | Docetaxel & Gemcitabine | Did not meet co-primary endpoints of ORR/TTP |
Georgoulias et al. 2003 | Not reported | Phase 3 (C) | Docetaxel | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 2
- Docetaxel (Taxotere) 100 mg/m2 IV once on day 1
21-day cycles
References
- Georgoulias V, Papadakis E, Alexopoulos A, Tsiafaki X, Rapti A, Veslemes M, Palamidas P, Vlachonikolis I; Greek Oncology Cooperative Group (GOCG) for Lung Cancer. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial. Lancet. 2001 May 12;357(9267):1478-84. link to original article PubMed
- ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Georgoulias V, Pallis AG, Kourousis C, Alexopoulos A, Ardavanis A, Agelidou A, Agelidou M, Toumbis M, Tzannes S, Pavlakou G, Ziotopoulos P, Tzelepatiotis E, Samaras N; Hellenic Oncology Research Group. Docetaxel versus docetaxel/cisplatin in patients with advanced non-small-cell lung cancer: preliminary analysis of a multicenter, randomized phase III study. Clin Lung Cancer. 2003 Mar;4(5):288-93. link to original article PubMed
- Update: Georgoulias V, Ardavanis A, Agelidou A, Agelidou M, Chandrinos V, Tsaroucha E, Toumbis M, Kouroussis C, Syrigos K, Polyzos A, Samaras N, Papakotoulas P, Christofilakis C, Ziras N, Alegakis A. Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol. 2004 Jul 1;22(13):2602-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Kubota K, Watanabe K, Kunitoh H, Noda K, Ichinose Y, Katakami N, Sugiura T, Kawahara M, Yokoyama A, Yokota S, Yoneda S, Matsui K, Kudo S, Shibuya M, Isobe T, Segawa Y, Nishiwaki Y, Ohashi Y, Niitani H; Japanese Taxotere Lung Cancer Study Group. Phase III randomized trial of docetaxel plus cisplatin versus vindesine plus cisplatin in patients with stage IV non-small-cell lung cancer: the Japanese Taxotere Lung Cancer Study Group. J Clin Oncol. 2004 Jan 15;22(2):254-61. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, Viñolas N, Paz-Ares L, Lopez-Vivanco G, Muñoz MA, Felip E, Alberola V, Camps C, Domine M, Sanchez JJ, Sanchez-Ronco M, Danenberg K, Taron M, Gandara D, Rosell R. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007 Jul 1;25(19):2747-54. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GLOB3: Tan EH, Rolski J, Grodzki T, Schneider CP, Gatzemeier U, Zatloukal P, Aitini E, Carteni G, Riska H, Tsai YH, Abratt R. Global Lung Oncology Branch trial 3 (GLOB3): final results of a randomised multinational phase III study alternating oral and iv vinorelbine plus cisplatin versus docetaxel plus cisplatin as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2009 Jul;20(7):1249-56. Epub 2009 Mar 10. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144066
- ELCWP-01041: Berghmans T, Lafitte JJ, Scherpereel A, Paesmans M, Lecomte J, Marco VG, Meert AP, Leclercq N, Sculier JP; European Lung Cancer Working Party. An ELCWP phase III trial comparing ifosfamide and cisplatin regimens in advanced NSCLC. Anticancer Res. 2013 Dec;33(12):5477-82. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00622349
- TCOG0701 CATS: Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S; Tokyo Cooperative Oncology Group. A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol. 2015 Jul;26(7):1401-8. Epub 2015 Apr 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000608
Cisplatin & Etoposide (EP)
PE: Platinol (Cisplatin) & Etoposide
EC: Etoposide & Cisplatin
Regimen variant #1, 60/360
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ruckdeschel et al. 1986 (ECOG E1581) | 1981-1983 | Phase 3 (E-switch-ic) | 1. CAMP 2. Cisplatin & Vindesine 3. MVP |
Did not meet primary endpoint |
Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator.
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Etoposide (Vepesid) 120 mg/m2 IV once per day on days 4, 6, 8
21-day cycles
Regimen variant #2, 75/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bonomi et al. 2000 (ECOG E5592) | 1993-08 to 1994-12 | Phase 3 (C) | Cisplatin & Paclitaxel | Seems to have inferior OS |
Belani et al. 2005 | 1995-05-19 to 1996-07-17 | Phase 3 (C) | Carboplatin & Paclitaxel | Might have superior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1
- Etoposide (Vepesid) 100 mg/m2 IV over 45 minutes once per day on days 1 to 3
21-day cycle for varying durations: 10 cycles (Belani et al. 2005); indefinitely (ECOG E5592)
Regimen variant #3, 100/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cardenal et al. 1999 | 1995-07 to 1996-06 | Phase 3 (C) | Cisplatin & Gemcitabine | Inferior TTP |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
- Etoposide (Vepesid) 100 mg/m2 IV over 60 minutes once per day on days 1 to 3
21-day cycle for up to 6 cycles
Regimen variant #4, 105/600
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Font et al. 1999 | 1993-1995 | Phase 3 (C) | PE; dose-dense | Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 35 mg/m2 IV once per day on days 1 to 3
- Etoposide (Vepesid) 200 mg/m2 IV once per day on days 1 to 3
28-day cycles
Regimen variant #5, 120/300
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Klastersky et al. 1990 (EORTC 07861) | 1987-1989 | Phase 3 (C) | Carboplatin & Etoposide | Might have superior ORR |
Comella et al. 1996 | 1993-1995 | Phase 3 (C) | Carboplatin, Cisplatin, Etoposide, Vinorelbine | Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 120 mg/m2 IV once on day 1
- Comella et al. 1996 gave 40 mg/m2 IV over 30 minutes once per day on days 1 to 3
- Etoposide (Vepesid) 100 mg/m2 IV over 45 minutes once per day on days 1 to 3
3- to 4-week cycles
References
- ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 07861: Klastersky J, Sculier JP, Lacroix H, Dabouis G, Bureau G, Libert P, Richez M, Ravez P, Vandermoten G, Thiriaux J, Cordier R, Finet C, Berchier MC, Sergysels R, Mommen P, Paesmans M. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organisation for Research and Treatment of Cancer Protocol 07861. J Clin Oncol. 1990 Sep;8(9):1556-62. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Comella P, Frasci G, De Cataldis G, Panza N, Cioffi R, Curcio C, Belli M, Bianco A, Ianniello G, Maiorino L, Della Vittoria M, Perchard J, Comella G; Gruppo Oncologico Campano. Cisplatin/carboplatin + etoposide + vinorelbine in advanced non-small-cell lung cancer: a multicentre randomised trial. Br J Cancer. 1996 Dec;74(11):1805-11. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Font A, Moyano AJ, Puerto JM, Tres A, Garcia-Giron C, Barneto I, Anton A, Sanchez JJ, Salvador A, Rosell R; Spanish Lung Cancer Group. Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group. Cancer. 1999 Feb 15;85(4):855-63. link to original article PubMed
- ECOG E5592: Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Belani CP, Lee JS, Socinski MA, Robert F, Waterhouse D, Rowland K, Ansari R, Lilenbaum R, Natale RB. Randomized phase III trial comparing cisplatin-etoposide to carboplatin-paclitaxel in advanced or metastatic non-small cell lung cancer. Ann Oncol. 2005 Jul;16(7):1069-75. Epub 2005 Apr 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin & Gemcitabine (GC)
GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)
Regimen variant #1, 70/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2007 | 2002-2004 | Phase 3 (E-de-esc) | 1a. Cisplatin & Paclitaxel x 6 1b. GC x 6 |
Non-inferior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 4 cycles
Regimen variant #2, 75/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Bissett et al. 2005 (AG-3340-017) | 1999-2001 | Phase 3 (C) | GC & Prinomastat | Did not meet primary endpoint of OS Median OS: 10.8 vs 11.5 mo |
|
Novello et al. 2007 | 2001-2004 | Phase 3 (C) | GC x 2, then gemcitabine x 3 | Inconclusive whether non-inferior OS (primary endpoint) OS: 52% vs 42% (HR 1.21, 90% CI 0.97-1.51) |
|
Manegold et al. 2011 | 2005-2007 | Phase 3 (C) | GC & PF-3512676 | Did not meet primary endpoint of OS Median OS: 10.7 vs 11 mo (HR 1.00, 95% CI 0.85-1.18) |
|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (C) | Pembrolizumab | Inferior OS | Inferior HRQoL |
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 varying durations: 4 to 6 cycles (KEYNOTE-024); 5 cycles (Novello et al. 2007); 6 cycles (AG-3340-017, Manegold et al. 2011)
Regimen variant #3, 80/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ohe et al. 2006 (FACS) | 2000-2002 | Phase 3 (E-switch-ic) | 1. Carboplatin & Paclitaxel | Inconclusive whether non-inferior OS (primary endpoint) |
2. Cisplatin & Irinotecan | Inconclusive whether non-inferior OS (primary endpoint) | |||
3. Cisplatin & Vinorelbine | Inconclusive whether non-inferior OS (primary endpoint) | |||
Takeda et al. 2009 (WJTOG0203) | 2003-2005 | Phase 3 (C) | Platinum doublet x 3, then Gefitinib | Might have inferior OS (primary endpoint) Median OS: 12.9 vs 13.7 mo (HR 1.16, 95% CI 0.97-1.39) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 cycles (WJTOG0203) or indefinitely (FACS)
Regimen variant #4, 80/1125
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wachters et al. 2003 | 1998-2002 | Phase 3 (C) | Epirubicin & Gemcitabine | Did not meet primary endpoint of PFS Median PFS: 26 vs 23 wk |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 3 hours once on day 2
- Gemcitabine (Gemzar) 1125 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for up to 5 cycles
Regimen variant #5, 80/1200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Gridelli et al. 2003 (NCIC-CTG BR.14) | 1998-2001 | Phase 3 (C) | Gemcitabine & Vinorelbine | Might have superior OS | |
Zatloukal et al. 2003 | 1999-2001 | Phase 3 (C) | GCb | Did not meet primary endpoint of grade 3/4 toxicity | |
Gridelli et al. 2007 (GECO) | 2003-2005 | Phase 3 (C) | 1. GC & Rofecoxib 2. Cisplatin & Gemcitabine; PCI gemcitabine 3. GC & Rofecoxib; PCI gemcitabine |
Did not meet primary endpoint of OS | |
Gridelli et al. 2012 (TORCH) | 2006-2009 | Phase 3 (C) | Erlotinib | Seems to have superior OS Median OS: 11.6 vs 8.7 mo (HR 0.81, 95% CI 0.68-0.96) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1, given second
- Gemcitabine (Gemzar) 1200 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
21-day cycle for up to 6 cycles
Subsequent treatment
- TORCH, at progression: Second-line erlotinib
Regimen variant #6, 80/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Giaccone et al. 2004 (INTACT 1) | 2000-05 to 2001-03 | Phase 3 (C) | 1. GC & Gefitinib; 250 mg/day 2. GC & Gefitinib; 500 mg/day |
Did not meet primary endpoint of OS |
Gatzemeier et al. 2007 (TALENT) | 2001-11 to 2002-09 | Phase 3 (C) | GC & Erlotinib | Did not meet primary endpoint of OS Median OS: 44.1 vs 43 wk (HR 0.94, 95% CI 0.81-1.11) |
Boni et al. 2012 (FAST) | 2001-2006 | Phase 3 (C) | 1. GIN 2. GN |
Seems to have superior OS |
3. GIP | Did not meet primary endpoint of OS | |||
Paz-Ares et al. 2006 | 2002-2004 | Phase 3 (C) | GC & Aprinocarsen | Did not meet primary endpoint of OS Median OS: 10.4 vs 10 mo (HR 0.95, 95% CI 0.80-1.14) |
Ferry et al. 2017 (BTOG2) | 2005-2009 | Phase 3 (E-esc) | 1. GC; GC50 | Seems to have superior OS (primary endpoint) |
2. GCb6 | Non-inferior OS (primary endpoint) | |||
Pérol et al. 2012 (IFCT-GFPC 0502) | 2006-2009 | Non-randomized part of phase 3 RCT |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1, given second
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
21-day cycle for varying durations: 4 cycles (BTOG2, IFCT-GFPC 0502); 6 cycles (FAST, INTACT 1, Paz-Ares et al. 2006, TALENT)
Subsequent treatment
- IFCT-GFPC 0502: Erlotinib versus gemcitabine switch maintenance versus observation
Regimen variant #7, 100/1000 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ridolfi et al. 2011 | 2000-2004 | Phase 3 (C) | GC & LD IL-2 | Did not meet primary endpoint of OS OS12: 51% vs 45% |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #8, 100/1000 q4wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Crinò et al. 1999 | 1995-1997 | Phase 3 (E-switch-ic) | MIC | Seems to have superior ORR |
Sandler et al. 2000 | 1995-1997 | Phase 3 (E-RT-esc) | Cisplatin | Superior OS |
Schiller et al. 2002 (ECOG E1594) | 1996-1999 | Phase 3 (E-switch-ic) | 1. Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
2. Cisplatin & Docetaxel | Did not meet primary endpoint of OS | |||
3. Cisplatin & Paclitaxel | Superior PFS | |||
Scagliotti et al. 2008 (JMDB) | 2004-07 to 2005-12 | Phase 3 (C) | Cisplatin & Pemetrexed | Seems to have non-inferior OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 30 to 120 minutes once on day 1 or 2, given second
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 to 60 minutes once per day on days 1, 8, 15
28-day cycle for varying durations: 6 cycles (Sandler et al. 2000, JMDB); indefinitely (Crinò et al. 1999, ECOG E1594)
Regimen variant #9, 100/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cardenal et al. 1999 | 1995-07 to 1996-06 | Phase 3 (E-RT-switch-ic) | Cisplatin & Etoposide | Superior TTP |
Alberola et al. 2003 | 1998-2000 | Phase 3 (C) | 1. CGV 2. GV-VI |
Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #10, 100/1400
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gebbia et al. 2003 | Not reported | Phase 3 (E-switch-ic) | Cisplatin & Vinorelbine | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1400 mg/m2 IV once per day on days 1 & 8
28-day cycles
References
- Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, Barneto I, Lomas M, García M, Lianes P, Montalar J, Vadell C, González-Larriba JL, Nguyen B, Artal A, Rosell R. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 1999 Jan;17(1):12-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Crinò L, Scagliotti GV, Ricci S, De Marinis F, Rinaldi M, Gridelli C, Ceribelli A, Bianco R, Marangolo M, Di Costanzo F, Sassi M, Barni S, Ravaioli A, Adamo V, Portalone L, Cruciani G, Masotti A, Ferrara G, Gozzelino F, Tonato M. Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: A randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol. 1999 Nov;17(11):3522-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, Mattson K, Manegold C, Palmer MC, Gregor A, Nguyen B, Niyikiza C, Einhorn LH. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2000 Jan;18(1):122-30. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Gebbia V, Galetta D, Caruso M, Verderame F, Pezzella G, Valdesi M, Borsellino N, Pandolfo G, Durini E, Rinaldi M, Loizzi M, Gebbia N, Valenza R, Tirrito ML, Varvara F, Colucci G; Gruppo Ocologico Italia Meridionale. Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale. Lung Cancer. 2003 Feb;39(2):179-89. link to original article dosing details in abstract have been reviewed by our editors PubMed
- NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00004100
- Alberola V, Camps C, Provencio M, Isla D, Rosell R, Vadell C, Bover I, Ruiz-Casado A, Azagra P, Jiménez U, González-Larriba JL, Diz P, Cardenal F, Artal A, Carrato A, Morales S, Sanchez JJ, de las Peñas R, Felip E, López-Vivanco G; Spanish Lung Cancer Group. Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial. J Clin Oncol. 2003 Sep 1;21(17):3207-13. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Zatloukal P, Petruzelka L, Zemanová M, Kolek V, Skricková J, Pesek M, Fojtů H, Grygárková I, Sixtová D, Roubec J, Horenková E, Havel L, Průsa P, Nováková L, Skácel T, Kůta M. Gemcitabine plus cisplatin vs gemcitabine plus carboplatin in stage IIIb and IV non-small cell lung cancer: a phase III randomized trial. Lung Cancer. 2003 Sep;41(3):321-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Wachters FM, Van Putten JW, Kramer H, Erjavec Z, Eppinga P, Strijbos JH, de Leede GP, Boezen HM, de Vries EG, Groen HJ. First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial. Br J Cancer. 2003 Oct 6;89(7):1192-9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- INTACT 1: Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, Gatzemeier U, Grous J, Ochs JS, Averbuch SD, Wolf MK, Rennie P, Fandi A, Johnson DH. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 1. J Clin Oncol. 2004 Mar 1;22(5):777-84. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- AG-3340-017: Bissett D, O'Byrne KJ, von Pawel J, Gatzemeier U, Price A, Nicolson M, Mercier R, Mazabel E, Penning C, Zhang MH, Collier MA, Shepherd FA. Phase III study of matrix metalloproteinase inhibitor prinomastat in non-small-cell lung cancer. J Clin Oncol. 2005 Feb 1;23(4):842-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00004199
- Paz-Ares L, Douillard JY, Koralewski P, Manegold C, Smit EF, Reyes JM, Chang GC, John WJ, Peterson PM, Obasaju CK, Lahn M, Gandara DR. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2006 Mar 20;24(9):1428-34. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Novello S, Bruzzi P, Barone C, Buosi R, Masotti A, Michetti G, Fioretti M, Barbera S, Spatafora M, Garetto L, Mazzanti P, Dongiovanni V, Selvaggi G, Crinò L, Scagliotti GV. Phase III study in stage IV non-small-cell lung cancer patients treated with two courses of cisplatin/gemcitabine followed by a randomization to three additional courses of the same combination or gemcitabine alone. Ann Oncol. 2007 May;18(5):903-8. Epub 2007 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- TALENT: Gatzemeier U, Pluzanska A, Szczesna A, Kaukel E, Roubec J, De Rosa F, Milanowski J, Karnicka-Mlodkowski H, Pesek M, Serwatowski P, Ramlau R, Janaskova T, Vansteenkiste J, Strausz J, Manikhas GM, Von Pawel J. Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol. 2007 Apr 20;25(12):1545-52. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GECO: Gridelli C, Gallo C, Ceribelli A, Gebbia V, Gamucci T, Ciardiello F, Carozza F, Favaretto A, Daniele B, Galetta D, Barbera S, Rosetti F, Rossi A, Maione P, Cognetti F, Testa A, Di Maio M, Morabito A, Perrone F; GECO investigators. Factorial phase III randomised trial of rofecoxib and prolonged constant infusion of gemcitabine in advanced non-small-cell lung cancer: the GEmcitabine-COxib in NSCLC (GECO) study. Lancet Oncol. 2007 Jun;8(6):500-12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00385606
- Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- JMDB: Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00087711
- WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144066
- Manegold C, van Zandwijk N, Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M, Serwatowski P, Krzakowski M, Jassem J, Tan EH, Benner RJ, Ingrosso A, Meech SJ, Readett D, Thatcher N. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol. 2012 Jan;23(1):72-7. Epub 2011 Apr 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Ridolfi L, Bertetto O, Santo A, Naglieri E, Lopez M, Recchia F, Lissoni P, Galliano M, Testore F, Porta C, Maglie M, Dall'agata M, Fumagalli L, Ridolfi R. Chemotherapy with or without low-dose interleukin-2 in advanced non-small cell lung cancer: results from a phase III randomized multicentric trial. Int J Oncol. 2011 Oct;39(4):1011-7. Epub 2011 Jun 24. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FAST: Boni C, Tiseo M, Boni L, Baldini E, Recchia F, Barone C, Grossi F, Germano D, Matano E, Marini G, Labianca R, Di Costanzo F, Bagnulo A, Pennucci C, Caroti C, Mencoboni M, Zanelli F, Prochilo T, Cafferata MA, Ardizzoni A; Gruppo Oncologico Italiano di Ricerca Clinica. Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST). Br J Cancer. 2012 Feb 14;106(4):658-65. Epub 2012 Jan 12. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- TORCH: Gridelli C, Ciardiello F, Gallo C, Feld R, Butts C, Gebbia V, Maione P, Morgillo F, Genestreti G, Favaretto A, Leighl N, Wierzbicki R, Cinieri S, Alam Y, Siena S, Tortora G, Felletti R, Riccardi F, Mancuso G, Rossi A, Cantile F, Tsao MS, Saieg M, da Cunha Santos G, Piccirillo MC, Di Maio M, Morabito A, Perrone F. First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial. J Clin Oncol. 2012 Aug 20;30(24):3002-11. Epub 2012 Jul 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349219
- HRQoL analysis: Di Maio M, Leighl NB, Gallo C, Feld R, Ciardiello F, Butts C, Maione P, Gebbia V, Morgillo F, Wierzbicki R, Favaretto A, Alam Y, Cinieri S, Siena S, Bianco R, Riccardi F, Spatafora M, Ravaioli A, Felletti R, Fregoni V, Genestreti G, Rossi A, Mancuso G, Fasano M, Morabito A, Tsao MS, Signoriello S, Perrone F, Gridelli C. Quality of life analysis of TORCH, a randomized trial testing first-line erlotinib followed by second-line cisplatin/gemcitabine chemotherapy in advancednon-small-cell lung cancer. J Thorac Oncol. 2012 Dec;7(12):1830-1844. link to original article PubMed
- IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original articledosing details in manuscript have been reviewed by our editors PubMed NCT00300586
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- BTOG2: Ferry D, Billingham L, Jarrett H, Dunlop D, Woll PJ, Nicolson M, Shah R, Thompson J, Spicer J, Muthukumar D, Skailes G, Leonard P, Chetiyawardana AD, Wells P, Lewanski C, Crosse B, Hill M, Gaunt P, O'Byrne K. Carboplatin versus two doses of cisplatin in combination with gemcitabine in the treatment of advanced non-small-cell lung cancer: results from a British Thoracic Oncology Group randomised phase III trial. Eur J Cancer. 2017 Sep;83:302-312. Epub 2017 Aug 4. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00112710
Cisplatin & Gemcitabine (GC) & Cetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Butts et al. 2008 | Not reported | Randomized Phase 2 (E-esc) | 1a. GCb 1b. GC |
Non-comparative |
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
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once per day on days 8 & 15
- Cycles 2 to 6: 250 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for up to 6 cycles
References
- Butts CA, Bodkin D, Middleman EL, Englund CW, Ellison D, Alam Y, Kreisman H, Graze P, Maher J, Ross HJ, Ellis PM, McNulty W, Kaplan E, Pautret V, Weber MR, Shepherd FA. Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol. 2007 Dec 20;25(36):5777-84. Erratum in: J Clin Oncol. 2008 Jul 1;26(19): 3295. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin & Irinotecan (IC)
IP: Irinotecan & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Negoro et al. 2003 | 1995-1998 | Phase 3 (E-switch-ic) | 1. Cisplatin & Vindesine | Did not meet primary endpoint of OS |
2. Irinotecan | Not reported | |||
Ohe et al. 2006 (FACS) | 2000-2002 | Phase 3 (C) | 1. Carboplatin & Paclitaxel | Inconclusive whether non-inferior OS |
2. Cisplatin & Gemcitabine | Inconclusive whether non-inferior OS | |||
3. Cisplatin & Vinorelbine | Inconclusive whether non-inferior OS | |||
Takeda et al. 2009 (WJTOG0203) | 2003-2005 | Phase 3 (C) | Platinum doublet x 3, then Gefitinib | Might have inferior OS (primary endpoint) Median OS: 12.9 vs 13.7 mo (HR 1.16, 95% CI 0.97-1.39) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Irinotecan (Camptosar) 60 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for up to 6 cycles (WJTOG0203) or indefinitely (FACS & Negoro et al. 2003)
References
- Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144066
Cisplatin & Paclitaxel (TP)
PC: Paclitaxel & Cisplatin
Regimen variant #1, 70/175 x 4
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2007 | 2002-2004 | Phase 3 (E-de-esc) | 1a. Cisplatin & Paclitaxel x 6 1b. GC x 6 |
Non-inferior OS (primary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen variant #2, 70/175 x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Park et al. 2007 | 2002-2004 | Phase 3 (C) | 1a. Cisplatin & Paclitaxel x 4 1b. GC x 4 |
Non-inferior OS |
Shi et al. 2020 (PM-03-2015) | 2015-2018 | Phase 3 (C) | Cisplatin & Paclitaxel micellar | Inferior PFS |
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1, given second
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1, given first
21-day cycle for 6 cycles
Regimen variant #3, 75/135, q2wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Stathopoulos et al. 2010a | 2006-2008 | Phase 3 (C) | Liposomal Cisplatin & Paclitaxel | Did not meet secondary endpoints | More toxic |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1, given second
- Paclitaxel (Taxol) 135 mg/m2 IV over 3 hours once on day 1, given first
14-day cycle for up to 9 cycles
Regimen variant #4, 75/135, q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bonomi et al. 2000 (ECOG E5592) | 1993-08 to 1994-12 | Phase 3 (E-RT-switch-ic) | Cisplatin & Etoposide | Seems to have superior OS |
Schiller et al. 2002 (ECOG E1594) | 1996-1999 | Phase 3 (C) | 1. Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
2. Cisplatin & Docetaxel | Did not meet primary endpoint of OS | |||
3. Cisplatin & Gemcitabine | Inferior PFS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 2, given second
- Paclitaxel (Taxol) 135 mg/m2 IV continuous infusion over 24 hours, started on day 1, given first
21-day cycles
Regimen variant #5, 75/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (C) | Investigator's choice of: 1a. CP & Cemiplimab 1b. TP & Cemiplimab 1c. Carboplatin, Pemetrexed, Cemiplimab 1d. Cisplatin, Pemetrexed, Cemiplimab |
Inferior OS |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Regimen variant #6, 80/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gatzemeier et al. 2000 | 1995-01 to 1996-04 | Phase 3 (E-esc) | Cisplatin | Did not meet primary endpoint of OS |
Smit et al. 2003 (EORTC 08975) | 1998-2000 | Phase 3 (C) | 1. Cisplatin & Gemcitabine 2. Gemcitabine & Paclitaxel |
Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 30 minutes once on day 1, given 1 hour after paclitaxel
- Paclitaxel (Taxol) 175 mg/m2 IV over 3 hours once on day 1, given first
21-day cycle for up to 6 cycles
Regimen variant #7, 80/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rosell et al. 2002 | 1996-04 to 1997-07 | Phase 3 (E-switch-ic) | Carboplatin & Paclitaxel | Non-inferior RR (primary endpoint) Seems to have superior OS (secondary endpoint) |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 30 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 10 cycles
References
- ECOG E5592: Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, Jiroutek M, Johnson D. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000 Feb;18(3):623-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Gatzemeier U, von Pawel J, Gottfried M, ten Velde GP, Mattson K, de Marinis F, Harper P, Salvati F, Robinet G, Lucenti A, Bogaerts J, Gallant G. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Oct 1;18(19):3390-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1594: Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; ECOG. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Rosell R, Gatzemeier U, Betticher DC, Keppler U, Macha HN, Pirker R, Berthet P, Breau JL, Lianes P, Nicholson M, Ardizzoni A, Chemaissani A, Bogaerts J, Gallant G. Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial. Ann Oncol. 2002 Oct;13(10):1539-49. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- EORTC 08975: Smit EF, van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, Smit H, Gaafar R, Biesma B, Manegold C, Neymark N, Giaccone G; EORTC Lung Cancer Group. Three-arm randomized study of two cisplatin-based regimens and paclitaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III trial of the European Organisation for Research and Treatment of Cancer Lung Cancer Group--EORTC 08975. J Clin Oncol. 2003 Nov 1;21(21):3909-17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003589
- Park JO, Kim SW, Ahn JS, Suh C, Lee JS, Jang JS, Cho EK, Yang SH, Choi JH, Heo DS, Park SY, Shin SW, Ahn MJ, Lee JS, Yun YH, Lee JW, Park K. Phase III trial of two versus four additional cycles in patients who are nonprogressive after two cycles of platinum-based chemotherapy in non small-cell lung cancer. J Clin Oncol. 2007 Nov 20;25(33):5233-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Stathopoulos GP, Antoniou D, Dimitroulis J, Michalopoulou P, Bastas A, Marosis K, Stathopoulos J, Provata A, Yiamboudakis P, Veldekis D, Lolis N, Georgatou N, Toubis M, Pappas Ch, Tsoukalas G. Liposomal cisplatin combined with paclitaxel versus cisplatin and paclitaxel in non-small-cell lung cancer: a randomized phase III multicenter trial. Ann Oncol. 2010 Nov;21(11):2227-32. Epub 2010 May 3. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- PM-03-2015: Shi M, Gu A, Tu H, Huang C, Wang H, Yu Z, Wang X, Cao L, Shu Y, Wang H, Yang R, Li X, Chang J, Hu Y, Shen P, Hu Y, Guo Z, Tao M, Zhang Y, Liu X, Sun Q, Zhang X, Jiang Z, Zhao J, Chen F, Yu H, Zhang W, Sun J, Li D, Zhou J, Han B, Wu YL. Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial. Ann Oncol. 2021 Jan;32(1):85-96. Epub 2020 Oct 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02667743
- EMPOWER-Lung 3 part 2: Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Li S, McGuire K, Kaul M, Paccaly A, Quek RGW, Gao B, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Gullo G, Rietschel P. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022 Nov;28(11):2374-2380. Epub 2022 Aug 25. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03409614
- PRO analysis: Makharadze T, Quek RGW, Melkadze T, Gogishvili M, Ivanescu C, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Konidaris G, Rietschel P, Gullo G. Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3. Cancer. 2023 Jul 15;129(14):2256-2265. Epub 2023 May 8. link to original article PubMed
Cisplatin & Paclitaxel (TP) & Cemiplimab
TP & Cemiplimab: Taxol (Paclitaxel), Platinol (Cisplatin), Cemiplimab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gogishvili et al. 2022 (EMPOWER-Lung 3 part 2) | 2019-06-17 to 2020-09-30 | Phase 3 (E-RT-esc) | Investigator's choice of: 1a. CP 1b. Cisplatin & Paclitaxel |
Superior OS (primary endpoint) Median OS: 21.9 vs 13 mo (HR 0.71, 95% CI 0.53-0.93) |
Note: In EMPOWER-Lung 3 part 2, patients with nonsquamous histology had additional treatment options; see the histology-specific page for more information.
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 to 4: 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 to 4: 200 mg/m2 IV once on day 1
Immunotherapy
- Cemiplimab (Libtayo) 350 mg IV once on day 1
21-day cycle for up to 36 cycles (2 years)
References
- EMPOWER-Lung 3 part 2: Gogishvili M, Melkadze T, Makharadze T, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Li S, McGuire K, Kaul M, Paccaly A, Quek RGW, Gao B, Seebach F, Weinreich DM, Yancopoulos GD, Lowy I, Gullo G, Rietschel P. Cemiplimab plus chemotherapy versus chemotherapy alone in non-small cell lung cancer: a randomized, controlled, double-blind phase 3 trial. Nat Med. 2022 Nov;28(11):2374-2380. Epub 2022 Aug 25. link to original article dosing details in supplement have been reviewed by our editors link to PMC article PubMed NCT03409614
- PRO analysis: Makharadze T, Quek RGW, Melkadze T, Gogishvili M, Ivanescu C, Giorgadze D, Dvorkin M, Penkov K, Laktionov K, Nemsadze G, Nechaeva M, Rozhkova I, Kalinka E, Gessner C, Moreno-Jaime B, Passalacqua R, Konidaris G, Rietschel P, Gullo G. Quality of life with cemiplimab plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: Patient-reported outcomes from phase 3 EMPOWER-Lung 3. Cancer. 2023 Jul 15;129(14):2256-2265. Epub 2023 May 8. link to original article PubMed
Cisplatin & S-1
SP: S-1 & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kubota et al. 2015 (TCOG0701 CATS) | 2007-04 to 2008-12 | Phase 3 (E-switch-ooc) | DP | Non-inferior OS (primary endpoint) Median OS: 16.1 vs 17.1 mo (HR 1.013, 96.4% CI 0.84-1.23) |
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 8
- Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- Less than 1.25 m2: 40 mg PO twice per day on days 1 to 21
- BSA at least 1.25 m2 and less than 1.5 m2: 50 mg PO twice per day on days 1 to 21
- BSA 1.5 m2 or more: 60 mg PO twice per day on days 1 to 21
28- to 35-day cycle for 3 to 6 cycles
References
- TCOG0701 CATS: Kubota K, Sakai H, Katakami N, Nishio M, Inoue A, Okamoto H, Isobe H, Kunitoh H, Takiguchi Y, Kobayashi K, Nakamura Y, Ohmatsu H, Sugawara S, Minato K, Fukuda M, Yokoyama A, Takeuchi M, Michimae H, Gemma A, Kudoh S; Tokyo Cooperative Oncology Group. A randomized phase III trial of oral S-1 plus cisplatin versus docetaxel plus cisplatin in Japanese patients with advanced non-small-cell lung cancer: TCOG0701 CATS trial. Ann Oncol. 2015 Jul;26(7):1401-8. Epub 2015 Apr 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN000000608
Cisplatin & Vinorelbine (CVb)
CVb: Cisplatin & Vinorelbine
CV: Cisplatin & Vinorelbine
NP: Navelbine (Vinorelbine) & Platinol (Cisplatin)
PV: Platinol (Cisplatin) & Vinorelbine
VC: Vinorelbine & Cisplatin
Regimen variant #1, 75/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Martoni et al. 2005 | 1998-2003 | Phase 3 (E-switch-ic) | Cisplatin & Gemcitabine | Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 60 minutes once on day 1, given second
- Vinorelbine (Navelbine) 25 mg/m2 IV bolus once per day on days 1 & 8, given first
21-day cycle for up to 6 cycles
Subsequent treatment
- Vinorelbine maintenance
Regimen variant #2, 80/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ohe et al. 2006 (FACS) | 2000-2002 | Phase 3 (E-switch-ic) | 1. Carboplatin & Paclitaxel | Inconclusive whether non-inferior OS (primary endpoint) |
2. Cisplatin & Gemcitabine | Inconclusive whether non-inferior OS (primary endpoint) | |||
3. Cisplatin & Irinotecan | Inconclusive whether non-inferior OS (primary endpoint) | |||
Takeda et al. 2009 (WJTOG0203) | 2003-2005 | Phase 3 (C) | Platinum doublet x 3, then Gefitinib | Might have inferior OS (primary endpoint) Median OS: 12.9 vs 13.7 mo (HR 1.16, 95% CI 0.97-1.39) |
Pirker et al. 2009 (FLEX) | 2004-2006 | Phase 3 (C) | Cisplatin, Vinorelbine, Cetuximab | Seems to have inferior OS |
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 up to 6 cycles (FLEX; WJTOG0203) or indefinitely (FACS)
Regimen variant #3, 80/30, 2 out of 3 weeks vinorelbine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Gridelli et al. 2003 (NCIC-CTG BR.14) | 1998-2001 | Phase 3 (C) | Gemcitabine & Vinorelbine | Might have superior OS | |
Georgoulias et al. 2005 | 1999-2002 | Phase 3 (C) | Docetaxel & Gemcitabine | Did not meet primary endpoint of OS | |
Gebbia et al. 2008 | 2003-01 to 2004-12 | Phase 3 (C) | Cisplatin & Vinorelbine; 3 out of 4 weeks | Did not meet primary endpoint of OS Median OS: 10 vs 9.45 mo (HR 0.89, 95% CI 0.69-1.10) |
Less toxic |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 8
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for varying durations: 6 cycles (NCIC-CTG BR.14); 9 cycles (Georgoulias et al. 2005); indefinitely (Gebbia et al. 2008)
Regimen variant #4, 80/30, weekly vinorelbine
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Depierre et al. 1994 | 1989-1991 | Phase 3 (E-esc) | Vinorelbine | Superior TTP |
Souquet et al. 2002 (GLOB-1) | 1998-02 to 1999-06 | Phase 3 (C) | NIP | Did not meet primary endpoint of OS1 |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
Regimen variant #5, 100/25 q4wk/weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wozniak et al. 1998 (SWOG S9308) | 1993-1995 | Phase 3 (E-RT-esc) | Cisplatin | Superior OS |
Kelly et al. 2001 (SWOG 9509) | 1996-1998 | Phase 3 (C) | Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
Fossella et al. 2003 (TAX 326) | 1998-2000 | Phase 3 (C) | 1. Carboplatin & Docetaxel | Did not meet primary endpoint of OS |
2. Cisplatin & Docetaxel | Seems to have inferior OS | |||
Ramlau et al. 2008 (SPIRIT I) | 2003 to not reported | Phase 3 (C) | CVb & Bexarotene | Did not meet primary endpoint of OS Median OS: 9.9 vs 8.7 mo |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) 25 mg/m2 IV over 6 to 10 minutes once per day on days 1, 8, 15, 22
28-day cycle for varying durations: 6 cycles (TAX 326); 10 cycles (SWOG 9509); indefinitely (SPIRIT I, SWOG S9308)
Regimen variant #6, 100/25 q4wk/weekly --> bi-weekly
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Scagliotti et al. 2002 | 1998-2000 | Phase 3 (C) | 1. Carboplatin & Paclitaxel 2. Cisplatin & Gemcitabine |
Did not meet primary endpoint of ORR |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) as follows:
- Cycles 1 to 3: 25 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22
- Cycle 4 onwards: 25 mg/m2 IV over 30 minutes once per day on days 1 & 15
28-day cycles
Regimen variant #7, 100/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pujol et al. 2005 | 1999-2001 | Phase 3 (C) | Docetaxel & Gemcitabine | Did not meet primary endpoint of OS |
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 to 120 minutes once on day 1
- Vinorelbine (Navelbine) 30 mg/m2 IV over 10 to 20 minutes once per day on days 1, 8, 15, 22
28-day cycle for 6 cycles
Regimen variant #8, 120/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Le Chevalier et al. 1994 | 1989-1991 | Phase 3 (E-RT-esc) | 1. Cisplatin & Vindesine | Seems to have superior OS |
2. Vinorelbine | Superior OS | |||
Comella et al. 2000 | 1997-1999 | Phase 3 (C) | 1. Cisplatin & Gemcitabine | Not reported |
2. PGV | Inferior OS |
Note: in Comella et al. 2000, vinorelbine was given for a total of 10 weeks.
Chemotherapy
- Cisplatin (Platinol) 120 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) as follows:
- Cycle 1: 30 mg/m2 IV once per day on days 1, 8, 15, 22
- Cycle 2 onwards: 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
28-day course, then 42-day cycles (see note)
References
- Depierre A, Chastang C, Quoix E, Lebeau B, Blanchon F, Paillot N, Lemarie E, Milleron B, Moro D, Clavier J, Herman D, Tuchais E, Jacoulet P, Brechot JM, Cordier JF, Solal-Celigny P, Badri N, Besenval M. Vinorelbine versus vinorelbine plus cisplatin in advanced non-small cell lung cancer: a randomized trial. Ann Oncol. 1994 Jan;5(1):37-42. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, Riviere A, Lianes P, Chomy P, Cigolari S, Gottfried M, Ruffle P, Panizo A, Gaspard MH, Ravaioli A, Besenval M, Besson F, Martinez A, Berthaud P, Tursz T. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol. 1994 Feb;12(2):360-7. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SWOG S9308: Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, Albain KS, Kelly K, Taylor SA, Gandara DR, Livingston RB; SWOG. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol. 1998 Jul;16(7):2459-65. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, Maiorino L, Micillo E, Lorusso V, Di Rienzo G, Filippelli G, Lamberti A, Natale M, Bilancia D, Nicolella G, Di Nota A, Comella G; Southern Italy Cooperative Oncology Group. Randomized trial comparing cisplatin, gemcitabine, and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol. 2000 Apr;18(7):1451-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SWOG 9509: Kelly K, Crowley J, Bunn PA Jr, Presant CA, Grevstad PK, Moinpour CM, Ramsey SD, Wozniak AJ, Weiss GR, Moore DF, Israel VK, Livingston RB, Gandara DR. Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non--small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol. 2001 Jul 1;19(13):3210-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, Matano E, Boni C, Marangolo M, Failla G, Altavilla G, Adamo V, Ceribelli A, Clerici M, Di Costanzo F, Frontini L, Tonato M; Italian Lung Cancer Project. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol. 2002 Nov 1;20(21):4285-91. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GLOB-1: Souquet PJ, Tan EH, Rodrigues Pereira J, Van Klaveren R, Price A, Gatzemeier U, Jaworski M, Burillon JP, Aubert D. GLOB-1: a prospective randomised clinical phase III trial comparing vinorelbine-cisplatin with vinorelbine-ifosfamide-cisplatin in metastatic non-small-cell lung cancer patients. Ann Oncol. 2002 Dec;13(12):1853-61. Erratum in: Ann Oncol. 2003 Feb;14(2):347. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- TAX 326: Fossella F, Rodrigues Pereira J, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00004100
- Martoni A, Marino A, Sperandi F, Giaquinta S, Di Fabio F, Melotti B, Guaraldi M, Palomba G, Preti P, Petralia A, Artioli F, Picece V, Farris A, Mantovani L. Multicentre randomised phase III study comparing the same dose and schedule of cisplatin plus the same schedule of vinorelbine or gemcitabine in advanced non-small cell lung cancer. Eur J Cancer. 2005 Jan;41(1):81-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Georgoulias V, Ardavanis A, Tsiafaki X, Agelidou A, Mixalopoulou P, Anagnostopoulou O, Ziotopoulos P, Toubis M, Syrigos K, Samaras N, Polyzos A, Christou A, Kakolyris S, Kouroussis C, Androulakis N, Samonis G, Chatzidaki D. Vinorelbine plus cisplatin versus docetaxel plus gemcitabine in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2005 May 1;23(13):2937-45. Epub 2005 Feb 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Pujol JL, Breton JL, Gervais R, Rebattu P, Depierre A, Morère JF, Milleron B, Debieuvre D, Castéra D, Souquet PJ, Moro-Sibilot D, Lemarié E, Kessler R, Janicot H, Braun D, Spaeth D, Quantin X, Clary C. Gemcitabine-docetaxel versus cisplatin-vinorelbine in advanced or metastatic non-small-cell lung cancer: a phase III study addressing the case for cisplatin. Ann Oncol. 2005 Apr;16(4):602-10. Epub 2005 Mar 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FACS: Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S, Nishiwaki Y, Saijo N, Ariyoshi Y, Fukuoka M. Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: four-arm cooperative study in Japan. Ann Oncol. 2007 Feb;18(2):317-23. Epub 2006 Nov 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Gebbia V, Galetta D, Lorusso V, Caruso M, Verderame F, Pezzella G, Borsellino N, Durini E, Valenza R, Agostara B, Colucci G; Gruppo Oncologico Italia Meridionale. Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the GOIM (Gruppo Oncologico Italia Meridionale). Lung Cancer. 2008 Sep;61(3):369-77. Epub 2008 Mar 4. link to original article dosing details in abstract have been reviewed by our editors PubMed
- SPIRIT I: Ramlau R, Zatloukal P, Jassem J, Schwarzenberger P, Orlov SV, Gottfried M, Rodrigues Pereira J, Temperley G, Negro-Vilar R, Rahal S, Zhang JK, Negro-Vilar A, Dziewanowska ZE. Randomized phase III trial comparing bexarotene (L1069-49)/cisplatin/vinorelbine with cisplatin/vinorelbine in chemotherapy-naive patients with advanced or metastatic non-small-cell lung cancer: SPIRIT I. J Clin Oncol. 2008 Apr 10;26(11):1886-92. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00050973
- FLEX: Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00148798
- WJTOG0203: Takeda K, Hida T, Sato T, Ando M, Seto T, Satouchi M, Ichinose Y, Katakami N, Yamamoto N, Kudoh S, Sasaki J, Matsui K, Takayama K, Kashii T, Iwamoto Y, Sawa T, Okamoto I, Kurata T, Nakagawa K, Fukuoka M. Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a West Japan Thoracic Oncology Group trial (WJTOG0203). J Clin Oncol. 2010 Feb 10;28(5):753-60. Epub 2009 Dec 28. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00144066
Cisplatin, Vinorelbine, Cetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pirker et al. 2009 (FLEX) | 2004-2006 | Phase 3 (E-esc) | Cisplatin & Vinorelbine | Seems to have superior OS (primary endpoint) Median OS: 11.3 vs 10.1 mo (HR 0.87, 95% CI 0.76-0.996) |
Chemotherapy
- Cisplatin (Platinol) as follows:
- Cycles 1 up to 6: 80 mg/m2 IV once on day 1
- Vinorelbine (Navelbine) as follows:
- Cycles 1 up to 6: 25 mg/m2 IV once per day on days 1 & 8
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15
- Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
21-day cycles
References
- FLEX: Pirker R, Rodrigues Pereira J, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00148798
Docetaxel & Vinorelbine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Miller et al. 2000 | 1997-1998 | Phase 2 |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1, given second
- Vinorelbine (Navelbine) 45 mg/m2 IV over 6 to 10 minutes once on day 1, given first
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO every 12 hours for 5 doses, starting on day -1
- Filgrastim (Neupogen) 5 mcg/kg SC once per day for at least 6 days, starting on day 3
- Ciprofloxacin (Cipro) (dose note specified) PO twice per day on days 3 to 10
14-day cycles
References
- Miller VA, Krug LM, Ng KK, Pizzo B, Perez W, Heelan RT, Kris MG. Phase II trial of docetaxel and vinorelbine in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Mar;18(6):1346-50. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Durvalumab & Tremelimumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
de Castro et al. 2022 (NEPTUNE) | 2015 to not reported | Phase 3 (E-switch-ooc) | Platinum doublet chemotherapy | Might have superior OS (primary endpoint) Median OS: 11.7 vs 9.1 mo (HR 0.71, 95% CI 0.49-1.05) |
Immunotherapy
- Durvalumab (Imfinzi) 20 mg/kg IV once on day 1
- Tremelimumab (Imjudo) as follows:
- Cycles 1 up to 4: 1 mg/kg IV once on day 1
28-day cycles
References
- NEPTUNE: de Castro G Jr, Rizvi NA, Schmid P, Syrigos K, Martin C, Yamamoto N, Cheng Y, Moiseyenko V, Summers Y, Vynnychenko I, Lee SY, Bryl M, Zer A, Erman M, Timcheva C, Raja R, Naicker K, Scheuring U, Walker J, Mann H, Chand V, Mok T; NEPTUNE Investigators. NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC. J Thorac Oncol. 2023 Jan;18(1):106-119. Epub 2022 Oct 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02542293
Gemcitabine & Paclitaxel
GT: Gemcitabine & Taxol (Paclitaxel)
GP: Gemcitabine & Paclitaxel
Regimen variant #1, 1000/125
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Comella et al. 2006 (SICOG 0101) | 2001-2005 | Phase 3 (C) | 1. GV 2. PGT 3. PGV |
Did not meet primary endpoint of OS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Paclitaxel (Taxol) 125 mg/m2 IV over 60 minutes once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #2, 1000/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kosmidis et al. 2002 | 1998-2000 | Phase 3 (E-switch-ic) | Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
Kosmidis et al. 2007 | 2000-2004 | Phase 3 (E-switch-ic) | Carboplatin & Gemcitabine | Did not meet primary endpoint of OS Median OS: 10.49 vs 9.97 mo |
Treat et al. 2009 (ALPHA A1-99002L) | 2000-2005 | Phase 3 (E-switch-ic) | CP]] | Did not meet primary endpoint of OS |
Kosmidis et al. 2010 | 2004-2008 | Phase 3 (C) | Paclitaxel & Vinorelbine | Superior OS (primary endpoint) Median OS: 11.1 vs 8.6 mo (aHR 0.76, 95% CI 0.61-0.94) |
Note: In Kosmidis et al. 2007, treatment was continued until maximum response plus 2 cycles, or up to 6 cycles in the case of stable disease.
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
- Paclitaxel (Taxol) 200 mg/m2 IV over 3 hours once on day 1
21-day cycle of varying durations: 6 cycles (ALPHA A1-99002L); until maximum response plus 2 cycles (Kosmidis et al. 2007); indefinitely (Kosmidis et al. 2002, Kosmidis et al. 2010)
References
- Kosmidis P, Mylonakis N, Nicolaides C, Kalophonos C, Samantas E, Boukovinas J, Fountzilas G, Skarlos D, Economopoulos T, Tsavdaridis D, Papakostas P, Bacoyiannis C, Dimopoulos M. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial. J Clin Oncol. 2002 Sep 1;20(17):3578-85. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Kosmidis PA, Kalofonos HP, Christodoulou C, Syrigos K, Makatsoris T, Skarlos D, Bakogiannis C, Nicolaides C, Bafaloukos D, Bamias A, Samantas E, Xiros N, Boukovinas I, Fountzilas G, Dimopoulos MA; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus carboplatin and gemcitabine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group. Ann Oncol. 2008 Jan;19(1):115-22. Epub 2007 Oct 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SICOG 0101: Comella P, Filippelli G, De Cataldis G, Massidda B, Frasci G, Maiorino L, Putzu C, Mancarella S, Palmeri S, Cioffi R, Roselli M, Buzzi F, Milia V, Gambardella A, Natale D, Bianco M, Ghiani M, Masullo P; Southern Italy Cooperative Oncology Group. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann Oncol. 2007 Feb;18(2):324-30. Epub 2006 Oct 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ALPHA A1-99002L: Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, Ansari R, Gillenwater HH, Rowland KM, Comis RL, Obasaju CK, Belani CP; Alpha Oncology Research Network. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010 Mar;21(3):540-7. Epub 2009 Oct 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00054392
- Kosmidis PA, Fountzilas G, Eleftheraki AG, Kalofonos HP, Pentheroudakis G, Skarlos D, Dimopoulos MA, Bafaloukos D, Pectasides D, Samantas E, Boukovinas J, Lambaki S, Katirtzoglou N, Bakogiannis C, Syrigos KN; Hellenic Cooperative Oncology Group. Paclitaxel and gemcitabine versus paclitaxel and vinorelbine in patients with advanced non-small-cell lung cancer: a phase III study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2011 Apr;22(4):827-34. Epub 2010 Sep 29. link to original article dosing details in abstract have been reviewed by our editors PubMed ACTRN12609000946213
Gemcitabine & Vinorelbine
VG: Vinorelbine & Gemcitabine
GV: Gemcitabine & Vinorelbine
G+V: Gemcitabine & Vinorelbine
Regimen variant #1, 1000/25, 2 weeks out of 3 (IV vinorelbine)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Laack et al. 2004 | 1999-2001 | Phase 3 (E-de-esc) | GVP | Did not meet primary endpoint of OS |
Tan et al. 2005 (GLOB 2) | 2000-2002 | Phase 3 (E-switch-ic) | Carboplatin & Vinorelbine | Did not meet primary endpoint of ORR |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Vinorelbine (Navelbine) 25 mg/m2 IV over 15 minutes once per day on days 1 & 8, given second
Supportive therapy
- "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."
21-day cycle for varying durations: 6 cycles (GLOB 2); indefinitely (Laack et al. 2004)
Regimen variant #2, 1000/25, 3 weeks out of 4 (IV vinorelbine)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Greco et al. 2007 (SCRI LUN 54) | 1998-2005 | Phase 3 (E-switch-ic) | PCG | Did not meet primary endpoint of OS | Less toxic |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
Regimen variant #3, 1000/60 (PO vinorelbine)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fløtten et al. 2012 | 2007-2009 | Phase 3 (E-switch-ic) | Carboplatin & Vinorelbine | Did not meet primary endpoint of OS |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 60 mg/m2 PO once per day on days 1 & 8
21-day cycle for 3 cycles
Regimen variant #4, 1200/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Frasci et al. 2001 | Not reported | Phase 3 (E-esc) | Vinorelbine | Superior OS |
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycles
References
- Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, DeCataldis G, Belli M, Iannelli N, Massidda B, Mascia V, Comella G, De Lena M; Southern Italy Cooperative Oncology Group. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced non-small cell lung cancer: a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer. 2001 Dec;34 Suppl 4:S65-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- NCIC-CTG BR.14: Gridelli C, Gallo C, Shepherd FA, Illiano A, Piantedosi F, Robbiati SF, Manzione L, Barbera S, Frontini L, Veltri E, Findlay B, Cigolari S, Myers R, Ianniello GP, Gebbia V, Gasparini G, Fava S, Hirsh V, Bezjak A, Seymour L, Perrone F; Italian GEMVIN Investigators; NCIC-CTG. Gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer: a phase III trial of the Italian GEMVIN Investigators and the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2003 Aug 15;21(16):3025-34. Epub 2003 Jul 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00004100
- Laack E, Dickgreber N, Müller T, Knuth A, Benk J, Lorenz C, Gieseler F, Dürk H, Engel-Riedel W, Dalhoff K, Kortsik C, Graeven U, Burk M, Dierlamm T, Welte T, Burkholder I, Edler L, Hossfeld DK; German and Swiss Lung Cancer Study Group. Randomized phase III study of gemcitabine and vinorelbine versus gemcitabine, vinorelbine, and cisplatin in the treatment of advanced non-small-cell lung cancer: from the German and Swiss Lung Cancer Study Group. J Clin Oncol. 2004 Jun 15;22(12):2348-56. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GLOB 2: Tan EH, Szczesna A, Krzakowski M, Macha HN, Gatzemeier U, Mattson K, Wernli M, Reiterer P, Hui R, Pawel JV, Bertetto O, Pouget JC, Burillon JP, Parlier Y, Abratt R; GLOB 2 group. Randomized study of vinorelbine--gemcitabine versus vinorelbine--carboplatin in patients with advanced non-small cell lung cancer. Lung Cancer. 2005 Aug;49(2):233-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- SICOG 0101: Comella P, Filippelli G, De Cataldis G, Massidda B, Frasci G, Maiorino L, Putzu C, Mancarella S, Palmeri S, Cioffi R, Roselli M, Buzzi F, Milia V, Gambardella A, Natale D, Bianco M, Ghiani M, Masullo P; Southern Italy Cooperative Oncology Group. Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101). Ann Oncol. 2007 Feb;18(2):324-30. Epub 2006 Oct 27. link to original article PubMed
- SCRI LUN 54: Greco FA, Spigel DR, Kuzur ME, Shipley D, Gray JR, Thompson DS, Burris HA, Yardley DA, Pati A, Webb CD, Gandhi JG, Hainsworth JD. Paclitaxel/Carboplatin/gemcitabine versus gemcitabine/vinorelbine in advanced non-small-cell lung cancer: a phase II/III study of the Minnie Pearl Cancer Research Network. Clin Lung Cancer. 2007 Sep;8(8):483-7. link to original article PubMed NCT00193362
- Fløtten Ø, Grønberg BH, Bremnes R, Amundsen T, Sundstrøm S, Rolke H, Hornslien K, Wentzel-Larsen T, Aasebø U, von Plessen C; Norwegian Lung Cancer Study Group. Vinorelbine and gemcitabine vs vinorelbine and carboplatin as first-line treatment of advanced NSCLC: a phase III randomised controlled trial by the Norwegian Lung Cancer Study Group. Br J Cancer. 2012 Jul 24;107(3):442-7. Epub 2012 Jul 3. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00737867
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Carbone et al. 2017 (CheckMate 026) | 2014-03 to 2015-04 | Phase 3 (E-switch-ooc) | Platinum doublet | Did not meet primary endpoint of PFS Median PFS: 4.2 vs 5.9 mo (HR 1.15, 95% CI 0.91-1.45) |
Note: control arm patients in CheckMate 026 received investigator's choice of platinum doublet; the most commonly used regimen was carboplatin & paclitaxel.
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
- Notably, on 2016-09-13 FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.
14-day cycles
References
- CheckMate 026: Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA; CheckMate 026 Investigators. First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med. 2017 Jun 22;376(25):2415-2426. link to original articledosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02041533
- CheckMate 227: Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02477826
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Phase 3 (E-RT-switch-ooc) | Investigator's choice of: 1a. Carboplatin & Gemcitabine 1b. Carboplatin & Paclitaxel 1c. Carboplatin & Pemetrexed 1d. Cisplatin & Gemcitabine 1e. Cisplatin & Pemetrexed |
Superior PFS (primary endpoint) Median PFS: 10.3 vs 6 mo (HR 0.50, 95% CI 0.37-0.68) Superior OS1 (secondary endpoint) Median OS: 26.3 vs 13.4 mo (HR 0.62, 95% CI 0.48-0.81) |
Superior HRQoL |
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Phase 3 (E-RT-switch-ooc) | Investigator's choice of: 1a. Carboplatin & Paclitaxel 1b. Carboplatin & Pemetrexed |
Superior OS2 (co-primary endpoint) Median OS: 16.7 vs 12.1 mo (HR 0.81, 95% CI 0.71-0.93) |
|
Wu et al. 2020 (KEYNOTE-042 China Extension) | 2016-08-26 to 2018-01-04 | Phase 3 (E-switch-ooc) | Investigator's choice of: 1a. Carboplatin & Paclitaxel 1b. Carboplatin & Pemetrexed |
Superior OS2 (co-primary endpoint) Median OS: 24.5 vs 13.8 mo (HR 0.67, 95% CI 0.50-0.89) |
|
Boyer et al. 2021 (KEYNOTE-598) | 2018-01-12 to 2019-08-22 | Phase 3 (C) | Ipilimumab & Pembrolizumab | Did not meet co-primary endpoint of OS Median OS: 21.9 vs 21.4 mo (HR 0.92, 95% CI 0.73-1.18) Did not meet co-primary endpoint of PFS Median PFS: 8.4 vs 8.2 mo (HR 0.94, 95% CI 0.77-1.16) |
|
Awaiting publication (INTRAPID Lung 037) | 2018-2021 | Phase 3 (C) | Bintrafusp alfa | TBD if different co-primary endpoints of PFS/OS | |
Yang et al. 2023 (LEAP-007) | 2019-04-09 to 2021-01-28 | Phase 3 (C) | Lenvatinib & Pembrolizumab | Did not meet co-primary endpoint of OS Median OS: 16.4 vs 14.1 mo (HR 0.91, 95% CI 0.72-1.15) Inferior PFS (co-primary endpoint) Median PFS: 4.2 vs 6.6 mo (HR 1.28, 95% CI 1.05-1.56) |
Fewer grade 3 to 5 TRAEs: 24.4% vs 57.9% |
Awaiting publication (AdvanTIG-302) | 2021-ongoing | Phase 3 (C) | Ociperlimab & Tislelizumab | TBD if different co-primary endpoints of PFS/OS | |
Awaiting publication (MK-7684A-003) | 2021-ongoing | Phase 3 (C) | Pembrolizumab & Vibostolimab | TBD if different co-primary endpoints of PFS/OS | |
Awaiting publication (TROPION-Lung08) | 2022-ongoing | Phase 3 (C) | Datopotamab-DXd & Pembrolizumab | TBD if different co-primary endpoints of PFS/OS | |
Awaiting publication (EVOKE-03) | 2023-ongoing | Phase 3 (C) | Pembrolizumab & Sacituzumab govitecan | TBD if different co-primary endpoints of PFS/OS |
1Reported efficacy for KEYNOTE-024 is based on the 2021 update.
2Reported efficacy for KEYNOTE-042 & KEYNOTE-042 China Extension is for the population with TPS of 1% or more.
KEYNOTE-024 treatment choice for patients in the comparator arm was up to the investigators; most with nonsquamous histology received carboplatin & pemetrexed, whereas most with squamous histology received carboplatin & gemcitabine. Patients could receive a maximum of 35 cycles. ORR was 45% (95% CI: 37-53).
KEYNOTE-042 treatment choice for patients in the comparator arm was carboplatin & paclitaxel for patients with squamous histology, and carboplatin & pemetrexed for patients with nonsquamous histology.
Biomarker eligibility criteria
- KEYNOTE-024: PD-L1 to be expressed on at least 50% of tumor cells, no EGFR/ALK mutations
- KEYNOTE-042: PD-L1 to be expressed on at least 1% of tumor cells
- KEYNOTE-042 China Extension & LEAP-007: PD-L1 TPS of at least 1%
- KEYNOTE-598 & TROPION-Lung08: PD-L1 TPS of at least 50%; no sensitizing EGFR or ALK mutations
References
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- KEYNOTE-042: Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. link to original article PubMed NCT02220894
- Update: de Castro G Jr, Kudaba I, Wu YL, Lopes G, Kowalski DM, Turna HZ, Caglevic C, Zhang L, Karaszewska B, Laktionov KK, Srimuninnimit V, Bondarenko I, Kubota K, Mukherjee R, Lin J, Souza F, Mok TSK, Cho BC. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study. J Clin Oncol. 2023 Apr 10;41(11):1986-1991. Epub 2022 Oct 28. link to original article link to PMC article PubMed
- KEYNOTE-042 China Extension: Wu YL, Zhang L, Fan Y, Zhou J, Zhang L, Zhou Q, Li W, Hu C, Chen G, Zhang X, Zhou C, Dang T, Sadowski S, Kush DA, Zhou Y, Li B, Mok T. Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study. Int J Cancer. 2021 May 1;148(9):2313-2320. Epub 2020 Dec 9. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT03850444
- KEYNOTE-598: Boyer M, Şendur MAN, Rodríguez-Abreu D, Park K, Lee DH, Çiçin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jul 20;39(21):2327-2338. Epub 2021 Jan 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03302234
- LEAP-007: Yang JC, Han B, De La Mora Jiménez E, Lee JS, Koralewski P, Karadurmus N, Sugawara S, Livi L, Basappa NS, Quantin X, Dudnik J, Ortiz DM, Mekhail T, Okpara CE, Dutcus C, Zimmer Z, Samkari A, Bhagwati N, Csőszi T. Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial. J Thorac Oncol. 2024 Jun;19(6):941-953. Epub 2023 Dec 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03829332
- AdvanTIG-302: NCT04746924
- EVOKE-03: NCT05609968
- INTRAPID Lung 037: NCT03631706
- MK-7684A-003: NCT04738487
- TROPION-Lung08: NCT05215340
Advanced or metastatic disease, first-line, elderly or poor performance status
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lee et al. 2023 (IPSOS) | 2017-09-11 to 2019-09-23 | Phase 3 (E-switch-ooc) | 1a. Gemcitabine 1b. Vinorelbine |
Seems to have superior OS (primary endpoint) Median OS: 10.3 vs 9.2 mo (sHR 0.78, 95% CI 0.63-0.97) |
Eligibility criteria
- One of the following:
- ECOG PS 2 or 3
- Age 70 years or older with an ECOG PS 0-1 with substantial comorbidities or contraindications for platinum-doublet chemotherapy
References
- IPSOS: Lee SM, Schulz C, Prabhash K, Kowalski D, Szczesna A, Han B, Rittmeyer A, Talbot T, Vicente D, Califano R, Cortinovis D, Le AT, Huang D, Liu G, Cappuzzo F, Reyes Contreras J, Reck M, Palmero R, Mak MP, Hu Y, Morris S, Höglander E, Connors M, Biggane AM, Vollan HK, Peters S. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study. Lancet. 2023 Aug 5;402(10400):451-463. Epub 2023 Jul 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT03191786
Carboplatin & Gemcitabine (GCb)
CG: Carboplatin & Gemcitabine
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Biesma et al. 2011 (NVALT-3) | 2003-2006 | Phase 3 (E-switch-ic) | CP | Did not meet secondary endpoint of OS | Similar QoL (primary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 4 cycles
References
- NVALT-3: Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NTR925
Carboplatin & Paclitaxel (CP)
TC: Taxol (Paclitaxel) & Carboplatin
CP: Carboplatin & Paclitaxel
Regimen variant #1, 5/90
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (eNERGY) | 2018-2021 | Phase 3 (C) | Ipilimumab & Nivolumab | Did not meet primary endpoint of OS |
Eligibility criteria
- 70 years old or older and PS 0-2, or
- Younger than 70 years old and PS 2
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
21-day cycle for 4 cycles
Regimen variant #2, 5/175
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Biesma et al. 2011 (NVALT-3) | 2003-2006 | Phase 3 (E-switch-ic) | CG | Similar QoL (primary endpoint) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for up to 4 cycles
Regimen variant #3, 6/90
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Quoix et al. 2011 (IFCT-0501) | 2006-2009 | Phase 3 (E-esc) | 1a. Gemcitabine 1b. Vinorelbine |
Superior OS (primary endpoint) Median OS: 10.3 vs 6.2 mo (HR 0.64, 95% CI 0.52-0.78) |
Eligibility criteria
- Age 70 to 89 years old and ECOG PS 0–2
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 90 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy
- Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3-4 neutropenia
28-day cycle for up to 4 cycles
Regimen variant #4, 6/200
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lilenbaum et al. 2008 | 2002-2004 | Phase 3 (C) | Erlotinib | Superior OS Median OS: 9.7 vs 6.5 mo (HR 0.58, 95% CI 0.37-0.92) |
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 up to 4 cycles
Regimen variant #4, 6/225
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Langer et al. 2008 | 2002-12 to 2003-12 | Phase 3 (C) | Carboplatin & PPX | Did not meet primary endpoint of OS Median OS: 8 vs 7.9 mo (HR 1.03, 95% CI 0.83-1.28) |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 225 mg/m2 IV once on day 1
21-day cycles
References
- Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Langer CJ, O'Byrne KJ, Socinski MA, Mikhailov SM, Leśniewski-Kmak K, Smakal M, Ciuleanu TE, Orlov SV, Dediu M, Heigener D, Eisenfeld AJ, Sandalic L, Oldham FB, Singer JW, Ross HJ. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jun;3(6):623-30. link to original article dosing details in abstract have been reviewed by our editors PubMed
- NVALT-3: Biesma B, Wymenga AN, Vincent A, Dalesio O, Smit HJ, Stigt JA, Smit EF, van Felius CL, van Putten JW, Slaets JP, Groen HJ; Dutch Chest Physician Study Group. Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study. Ann Oncol. 2011 Jul;22(7):1520-7. Epub 2011 Jan 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NTR925
- IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00298415
- eNERGY: NCT03351361
Carboplatin & Pemetrexed
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zukin et al. 2013 (INCA-Lung001) | 2008-2011 | Phase 3 (E-esc) | Pemetrexed | Superior OS (primary endpoint) Median OS: 9.3 vs 5.3 mo (HR 0.62, 95% CI 0.46-0.83) |
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 up to 4 cycles
References
- INCA-Lung001: Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01836575
Carboplatin, Pemetrexed, Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2018 (ToPPS) | 2009-2013 | Randomized Phase 2 (E-esc) | 1. Pemetrexed 2. Pemetrexed & Bevacizumab |
PFS: 4.8 mo |
Chemotherapy
- 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
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Supportive therapy
- Premedications, Folic acid (Folate), and vitamin supplementation per standard guidelines
- Antiemetics per standard guidelines
21-day cycles
References
- ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00892710
Cisplatin & Gemcitabine (GC)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morabito et al. 2013 (CAPPA-2) | 2008-2012 | Phase 3 (E-esc) | Gemcitabine | Seems to have superior OS (primary endpoint) Median OS: 5.9 vs 3 mo (HR 0.52, 95% CI 0.28-0.98) |
Gridelli et al. 2018 (MILES-3) | 2011-2016 | Phase 3 (E-esc) | Gemcitabine | Might have superior OS (primary endpoint) Median OS: 9.6 vs 7.5 mo (HR 0.86, 95% CI 0.70-1.05) |
Eligibility criteria
- MILES-3: patients at least 70 years old
- CAPPA-2: patients aged 18 to 70 with ECOG PS = 2
Chemotherapy
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycle for up to 4 cycles
References
- CAPPA-2: Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00526643
- MILES-3: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article PubMed NCT01405586
Docetaxel monotherapy
Example orders
Regimen variant #1, 25 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tsukada et al. 2014 (JCOG0207) | 2003-2006 | Phase 3 (C) | Cisplatin & Docetaxel | Seems to have inferior OS (primary endpoint) Median OS: 10.7 vs 17 mo |
Note: This study was terminated early; see paper for details.
Regimen variant #2, 36 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hainsworth et al. 2007 | 2001-2006 | Phase 3 (C) | Docetaxel & Gemcitabine | Did not meet primary endpoint of OS Median OS: 5.1 vs 5.5 mo |
Regimen variant #3, 38 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Karampeazis et al. 2011 (HORG CT/03.07) | 2003-2008 | Phase 3 (E-switch-ic) | Vinorelbine | Might have superior OS (primary endpoint) Median OS: 6.07 vs 3.87 mo |
Chemotherapy
- Docetaxel (Taxotere) 38 mg/m2 IV over 60 minutes once per day on days 1 & 8
21-day cycle for up to 6 cycles
Regimen variant #4, 60 mg/m2 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kudoh et al. 2006 (WJTOG 9904) | 2000-2003 | Phase 3 (E-switch-ic) | Vinorelbine | Did not meet primary endpoint of OS Median OS: 14.3 vs 9.9 mo (HR 0.78, 95% CI 0.56-1.09) |
Abe et al. 2015 (JCOG0803/WJOG4307L) | 2008-2010 | Phase 3 (C) | Cisplatin & Docetaxel | Did not meet primary endpoint of OS OS12: 58.2% vs 54.5% (HR 0.85, 95% CI 0.59-1.20) |
Note: This is the PMDA-approved dose.
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1
21-day cycle for up to 4 cycles (WJTOG 9904) or indefinitely
References
- WJTOG 9904: Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00148291
- Hainsworth JD, Spigel DR, Farley C, Shipley DL, Bearden JD, Gandhi J, Houston GA, Greco FA. Weekly docetaxel versus docetaxel/gemcitabine in the treatment of elderly or poor performance status patients with advanced nonsmall cell lung cancer: a randomized phase 3 trial of the Minnie Pearl Cancer Research Network. Cancer. 2007 Nov 1;110(9):2027-34. link to original article dosing details in abstract have been reviewed by our editors PubMed
- HORG CT/03.07: Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00441922
- JCOG0207: Tsukada H, Yokoyama A, Goto K, Shinkai T, Harada M, Ando M, Shibata T, Ohe Y, Tamura T, Saijo N; Lung Cancer Study Group of the Japan Clinical Oncology Group (JCOG). Randomized controlled trial comparing docetaxel-cisplatin combination with weekly docetaxel alone in elderly patients with advanced non-small-cell lung cancer: Japan Clinical Oncology Group (JCOG) 0207. Jpn J Clin Oncol. 2015 Jan;45(1):88-95. Epub 2014 Nov 6. link to original article dosing details in abstract have been reviewed by our editors PubMed UMIN C000000146
- JCOG0803/WJOG4307L: Abe T, Takeda K, Ohe Y, Kudoh S, Ichinose Y, Okamoto H, Yamamoto N, Yoshioka H, Minato K, Sawa T, Iwamoto Y, Saka H, Mizusawa J, Shibata T, Nakamura S, Ando M, Yokoyama A, Nakagawa K, Saijo N, Tamura T. Randomized phase III trial comparing weekly docetaxel plus cisplatin versus docetaxel monotherapy every 3 weeks in elderly patients with advanced non-small-cell lung cancer: the intergroup trial JCOG0803/WJOG4307L. J Clin Oncol. 2015 Feb 20;33(6):575-81. Epub 2015 Jan 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed UMIN000001424
Gemcitabine monotherapy
Regimen variant #1, 1000 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Brien et al. 2008 | 2002-2004 | Phase 3 (C) | Paclitaxel poliglumex | Did not meet primary endpoint of OS Median OS: 6.6 vs 7.3 mo (HR 1.05, 95% CI 0.83-1.32) |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycle for up to 6 cycles
Regimen variant #2, 1150 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Quoix et al. 2011 (IFCT-0501) | 2006-2009 | Phase 3 (C) | Carboplatin & Paclitaxel | Inferior OS |
Eligibility criteria
- Age 70 to 89 years and ECOG PS 0–2
Chemotherapy
- Gemcitabine (Gemzar) 1150 mg/m2 IV once per day on days 1 & 8
Supportive therapy
- Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia
21-day cycle for up to 5 cycles
Regimen variant #3, 1200 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gridelli et al. 2003 (MILES) | 1997-2000 | Phase 3 (E-switch-ic) | 1. Gemcitabine & Vinorelbine | Did not meet primary endpoint of OS |
2. Vinorelbine | Did not meet primary endpoint of OS | |||
Morabito et al. 2013 (CAPPA-2) | 2008-2012 | Phase 3 (C) | Cisplatin & Gemcitabine | Seems to have inferior OS |
Gridelli et al. 2018 (MILES-3) | 2011-2016 | Phase 3 (C) | Cisplatin & Gemcitabine | Might have inferior OS |
Eligibility criteria
- MILES-3: patients at least 70 years old
- CAPPA-2: patients aged 18 to 70 with ECOG PS = 2
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV over 30 minutes once per day on days 1 & 8
Supportive therapy
- "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."
21-day cycle for varying durations: 4 cycles (CAPPA-2); 6 cycles (MILES, MILES-3)
Regimen variant #4, 1250 mg/m2, 2 out of 3 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Reynolds et al. 2009 (USO-03012) | 2004-2006 | Phase 3 (C) | Carboplatin & Gemcitabine | Did not meet primary endpoint of OS Median OS: 5.1 vs 6.7 mo |
Chemotherapy
- Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
21-day cycle for 6 cycles
References
- MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003447
- SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
- O'Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, Hotko YS, Ganul VL, Kostinsky IY, Eisenfeld AJ, Sandalic L, Oldham FB, Bandstra B, Sandler AB, Singer JW. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008 Jul;3(7):728-34. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- USO-03012: Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, Caton JR, Demarco LC, O'Rourke MA, Shaw Wright G, Boehm KA, Asmar L, Bromund J, Peng G, Monberg MJ, Bepler G. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol. 2009 Dec 1;27(34):5808-15. Epub 2009 Nov 2. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00190710
- IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00298415
- CAPPA-2: Morabito A, Gebbia V, Di Maio M, Cinieri S, Viganò MG, Bianco R, Barbera S, Cavanna L, De Marinis F, Montesarchio V, Costanzo R, Sandomenico C, Montanino A, Mancuso G, Russo P, Nacci A, Giordano P, Daniele G, Piccirillo MC, Rocco G, Gridelli C, Gallo C, Perrone F. Randomized phase III trial of gemcitabine and cisplatin vs gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung Cancer. 2013 Jul;81(1):77-83. Epub 2013 May 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00526643
- MILES-3: Gridelli C, Morabito A, Cavanna L, Luciani A, Maione P, Bonanno L, Filipazzi V, Leo S, Cinieri S, Ciardiello F, Burgio MA, Bilancia D, Cortinovis D, Rosetti F, Bianco R, Gebbia V, Artioli F, Bordonaro R, Fregoni V, Mencoboni M, Nelli F, Riccardi F, di Isernia G, Costanzo R, Rocco G, Daniele G, Signoriello S, Piccirillo MC, Gallo C, Perrone F. Cisplatin-based first-line treatment of elderly patients with advanced non-small-cell lung cancer: joint analysis of MILES-3 and MILES-4 phase III trials. J Clin Oncol. 2018 Sep 1;36(25):2585-2592. Epub 2018 Jul 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01405586
- IPSOS: Lee SM, Schulz C, Prabhash K, Kowalski D, Szczesna A, Han B, Rittmeyer A, Talbot T, Vicente D, Califano R, Cortinovis D, Le AT, Huang D, Liu G, Cappuzzo F, Reyes Contreras J, Reck M, Palmero R, Mak MP, Hu Y, Morris S, Höglander E, Connors M, Biggane AM, Vollan HK, Peters S. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study. Lancet. 2023 Aug 5;402(10400):451-463. Epub 2023 Jul 6. link to original article does not contain dosing details PubMed NCT03191786
Gemcitabine & Paclitaxel
GT: Gemcitabine & Taxol (Paclitaxel)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Comella et al. 2004 (SICOG 9909) | 1999-2003 | Phase 3 (E-esc) | 1. Gemcitabine 2. Paclitaxel |
Seems to have superior OS (primary endpoint) |
3. GV | Not reported |
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
- Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
21-day cycle for up to 6 cycles
References
- SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
Gemcitabine & Vinorelbine
GV: Gemcitabine & Vinorelbine
VG: Vinorelbine & Gemcitabine
Regimen variant #1, 1000/25
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gridelli et al. 2003 (MILES) | 1997-2000 | Phase 3 (E-esc) | 1. Gemcitabine | Did not meet primary endpoint of OS |
2. Vinorelbine | Did not meet primary endpoint of OS |
Eligibility criteria
- At least 70 years old
Chemotherapy
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 25 mg/m2 IV once per day on days 1 & 8
Supportive therapy
- "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."
21-day cycle for up to 6 cycles
Regimen variant #2, 1200/30
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Frasci et al. 2000 | 1997-1999 | Phase 3 (E-esc) | Vinorelbine | Superior OS |
Eligibility criteria
- At least 70 years old
Chemotherapy
- Gemcitabine (Gemzar) 1200 mg/m2 IV once per day on days 1 & 8
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
21-day cycle for up to 6 cycles
References
- Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, De Cataldis G, Iannelli A, Bilancia D, Belli M, Massidda B, Piantedosi F, Comella G, De Lena M. Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol. 2000 Jul;18(13):2529-36. link to original article dosing details in abstract have been reviewed by our editors PubMed
- MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003447
- SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
Pemetrexed monotherapy
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zukin et al. 2013 (INCA-Lung001) | 2008-2011 | Phase 3 (C) | Carboplatin & Pemetrexed | Inferior OS |
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
21-day cycle for up to 4 cycles
References
- INCA-Lung001: Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Serodio Da Rocha Baldotto C, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01836575
- ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00892710
Pemetrexed & Bevacizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Spigel et al. 2018 (ToPPS) | 2009-2013 | Randomized Phase 2 (E-esc) | 1. Pemetrexed 2. Carboplatin, Pemetrexed, Bevacizumab |
PFS: 4.0 mo |
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV once on day 1
Targeted therapy
- Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Supportive therapy
- Premedications, Folic acid (Folate), and vitamin supplementation per standard guidelines
- Antiemetics per standard guidelines
21-day cycles
References
- ToPPS: Spigel DR, Hainsworth JD, Joseph MJ, Shipley DL, Hagan MK, Thompson DS, Burris HA 3rd, Greco FA. Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2. Cancer. 2018 May 1;124(9):1982-1991. Epub 2018 Feb 16. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00892710
Vinorelbine monotherapy
Regimen variant #1, 25 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kudoh et al. 2006 (WJTOG 9904) | 2000-2003 | Phase 3 (C) | Docetaxel | Did not meet primary endpoint of OS |
Karampeazis et al. 2011 (HORG CT/03.07) | 2003-2008 | Phase 3 (E-switch-ic) | Docetaxel | Might have inferior OS (primary endpoint) |
Quoix et al. 2011 (IFCT-0501) | 2006-2009 | Phase 3 (C) | Carboplatin & Paclitaxel | Inferior OS |
Eligibility criteria
- IFCT-0501: Age 70 to 89 years and ECOG PS 0–2
Chemotherapy
- Vinorelbine (Navelbine) 25 mg/m2 IV over 30 minutes once per day on days 1 & 8
Supportive therapy
- Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia
21-day cycle for varying durations: 4 cycles (WJTOG 9904); 5 cycles (IFCT-0501); 6 cycles (HORG CT/03.07)
Regimen variant #2, 30 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gridelli et al. 1999 (ELVIS) | 1996-04 to 1997-11 | Phase 3 (E-esc) | Best supportive care | Seems to have superior OS |
Gridelli et al. 2003 (MILES) | 1997-2000 | Phase 3 (C) | 1. Gemcitabine | Did not meet primary endpoint of OS |
2. Gemcitabine & Vinorelbine | Did not meet primary endpoint of OS |
Note: These studies involved only patients at least 70 years old
Chemotherapy
- Vinorelbine (Navelbine) 30 mg/m2 IV once per day on days 1 & 8
Supportive therapy
- (varies depending on reference):
- ELVIS: Metoclopramide (Reglan) 20 mg IV bolus once per day on days 1 & 8, prior to vinorelbine
- MILES: "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."
21-day cycle for up to 6 cycles
References
- ELVIS: Gridelli C, Perrone F, Gallo C; Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- MILES: Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003447
- WJTOG 9904: Kudoh S, Takeda K, Nakagawa K, Takada M, Katakami N, Matsui K, Shinkai T, Sawa T, Goto I, Semba H, Seto T, Ando M, Satoh T, Yoshimura N, Negoro S, Fukuoka M. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small-cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol. 2006 Aug 1;24(22):3657-63. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00148291
- HORG CT/03.07: Karampeazis A, Vamvakas L, Agelidou A, Kentepozidis N, Chainis K, Chandrinos V, Vardakis N, Pallis AG, Christophyllakis C, Georgoulias V; Hellenic Oncology Research Group. Docetaxel vs vinorelbine in elderly patients with advanced non--small-cell lung cancer: a Hellenic Oncology Research Group randomized phase III study. Clin Lung Cancer. 2011 May;12(3):155-60. Epub 2011 Apr 27. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00441922
- IFCT-0501: Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00298415
- IPSOS: Lee SM, Schulz C, Prabhash K, Kowalski D, Szczesna A, Han B, Rittmeyer A, Talbot T, Vicente D, Califano R, Cortinovis D, Le AT, Huang D, Liu G, Cappuzzo F, Reyes Contreras J, Reck M, Palmero R, Mak MP, Hu Y, Morris S, Höglander E, Connors M, Biggane AM, Vollan HK, Peters S. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study. Lancet. 2023 Aug 5;402(10400):451-463. Epub 2023 Jul 6. link to original article does not contain dosing details PubMed NCT03191786
Maintenance after first-line therapy
Bevacizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Johnson et al. 2013 (ATLAS-NSCLC) | 2006-2009 | Phase 3 (C) | Erlotinib & Bevacizumab maintenance | Inferior PFS1 | Less toxic |
1While this arm was inferior in ATLAS, the authors noted that, due to toxicity, the "two-drug maintenance regimen will not lead to a new postchemotherapy standard of care."
Note: ATLAS should not be confused with the trials with the same name in breast cancer and in renal cell carcinoma.
Preceding treatment
- First-line DCb & Bevacizumab x 4 or GCb & Bevacizumab x 4 or PacCBev x 4 or DC & Bevacizumab x 4 or GC & Bevacizumab x 4 or CVb & Bevacizumab x 4
References
- ATLAS: Johnson BE, Kabbinavar F, Fehrenbacher L, Hainsworth J, Kasubhai S, Kressel B, Lin CY, Marsland T, Patel T, Polikoff J, Rubin M, White L, Yang JC, Bowden C, Miller V. ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing bevacizumab therapy with or without erlotinib, after completion of chemotherapy, with bevacizumab for first-line treatment of advanced non-small-cell lung cancer. J Clin Oncol. 2013 Nov 1;31(31):3926-34. Epub 2013 Oct 7. link to original article dosing details in supplement have been reviewed by our editors PubMed NCT00257608
Docetaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhang et al. 2021 (TFINE) | 2009-2011 | Phase 3 (E-esc) | Observation | Superior PFS (primary endpoint) Median PFS: 5.8 vs 3 mo (HR 0.57, 95% CI 0.40-0.80) |
References
- TFINE:' Zhang L, Lu S, Cheng Y, Hu Z, Wu YL, Chen Z, Chen G, Liu X, Yang J, Zhang L, Chen J, Huang M, Tao M, Cheng G, Huang C, Zhou C, Zhang W, Zhao H, Sun Y. Docetaxel maintenance therapy versus best supportive care after first-line chemotherapy with different dose docetaxel plus cisplatin for advanced non-small cell lung cancer (TFINE study, CTONG-0904): an open-label, randomized, phase III trial. Ann Transl Med. 2021 Feb;9(4):338. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01038661
Gemcitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Brodowicz et al. 2006 | 1999-2002 | Phase 3 (E-esc) | Observation | Superior TTP (primary endpoint) |
Pérol et al. 2012 (IFCT-GFPC 0502) | 2006-2009 | Phase 3 (E-esc) | 1. Erlotinib | Not reported |
2. Observation | Superior PFS (primary endpoint) Median PFS: 3.8 vs 1.9 mo (HR 0.56, 95% CI 0.44-0.72) |
Preceding treatment
- First-line Cisplatin & Gemcitabine x 4
References
- Brodowicz T, Krzakowski M, Zwitter M, Tzekova V, Ramlau R, Ghilezan N, Ciuleanu T, Cucevic B, Gyurkovits K, Ulsperger E, Jassem J, Grgic M, Saip P, Szilasi M, Wiltschke C, Wagnerova M, Oskina N, Soldatenkova V, Zielinski C, Wenczl M; Central European Cooperative Oncology Group. Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer. 2006 May;52(2):155-63. Epub 2006 Mar 29. link to original article dosing details in abstract have been reviewed by our editors PubMed
- IFCT-GFPC 0502: Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original articledosing details in manuscript have been reviewed by our editors PubMed NCT00300586
Ipilimumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Lynch et al. 2012 (CA184-041NSCLC) | 2008-2009 | Non-randomized part of phase 2 RCT |
Preceding treatment
- First-line Carboplatin, Paclitaxel, Ipilimumab x 6
References
- CA184-041NSCLC: Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00527735
Pembrolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Awaiting publication (ZEAL-1L) | 2020-ongoing | Phase 3 (C) | Niraparib & Pembrolizumab | TBD if different co-primary endpoints of PFS/OS |
Preceding treatment
- First-line platinum-based chemotherapy
References
- ZEAL-1L: NCT04475939
Pemetrexed monotherapy
Example orders
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ciuleanu et al. 2009 (JMEN) | 2005-2007 | Phase 3 (E-RT-esc) | Placebo | Superior PFS (primary endpoint) Median PFS: 4.3 vs 2.6 mo (HR 0.50, 95% CI 0.42-0.61) Superior OS (secondary endpoint) Median OS: 13.4 vs 10.6 mo (HR 0.79, 95% CI 0.65-0.95) |
Reck et al. 2016 (KEYNOTE-024) | 2014-09-19 to 2015-10-29 | Non-randomized part of phase 3 RCT | ||
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Non-randomized part of phase 3 RCT |
Preceding treatment
- JMEN: First-line platinum-based chemotherapy x 4
- KEYNOTE-024: First-line Carboplatin & Paclitaxel or Carboplatin & Pemetrexed or Cisplatin & Pemetrexed
- KEYNOTE-042: First-line Carboplatin & Pemetrexed x 6
Chemotherapy
- Pemetrexed (Alimta) 500 mg/m2 IV over 10 minutes once on day 1
Supportive therapy
- Folic acid (Folate)
- Cyanocobalamin (Vitamin B12)
- Dexamethasone (Decadron)
- "Investigators followed current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines for use of colony-stimulating factors and erythropoiesis-stimulating agents."
21-day cycles
References
- JMEN: Ciuleanu T, Brodowicz T, Zielinski C, Kim JH, Krzakowski M, Laack E, Wu YL, Bover I, Begbie S, Tzekova V, Cucevic B, Rodrigues Pereira J, Yang SH, Madhavan J, Sugarman KP, Peterson P, John WJ, Krejcy K, Belani CP. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet. 2009 Oct 24;374(9699):1432-40. Epub 2009 Sep 18. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00102804
- KEYNOTE-024: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. Epub 2016 Oct 8. link to original article link to supplementary appendix dosing details in manuscript have been reviewed by our editors PubMed NCT02142738
- HRQoL analysis: Brahmer JR, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Zhang J, Lubiniecki GM, Deitz AC, Rangwala R, Reck M. Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1600-1609. Epub 2017 Nov 9. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Vandormael K, Riccio A, Yang J, Pietanza MC, Brahmer JR. Updated analysis of KEYNOTE-024: pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 2019 Mar 1;37(7):537-546. Epub 2019 Jan 8. link to original article PubMed
- Update: Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. Epub 2021 Apr 19. link to original article link to PMC article PubMed
- KEYNOTE-042: Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. link to original article PubMed NCT02220894
- Update: de Castro G Jr, Kudaba I, Wu YL, Lopes G, Kowalski DM, Turna HZ, Caglevic C, Zhang L, Karaszewska B, Laktionov KK, Srimuninnimit V, Bondarenko I, Kubota K, Mukherjee R, Lin J, Souza F, Mok TSK, Cho BC. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study. J Clin Oncol. 2023 Apr 10;41(11):1986-1991. Epub 2022 Oct 28. link to original article link to PMC article PubMed
Advanced or metastatic disease, second-line
Cabozantinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Neal et al. 2016 (ECOG-ACRIN 1512) | 2013-2014 | Randomized Phase 2 (E-switch-ic) | 1. Cabozantinib & Erlotinib | Not reported |
2. Erlotinib | Superior PFS (primary endpoint) Median PFS: 4.3 vs 1.8 mo (HR 0.39, 80% CI 0.27-0.55) |
References
- ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01708954
Cabozantinib & Erlotinib
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Neal et al. 2016 (ECOG-ACRIN 1512) | 2013-2014 | Randomized Phase 2 (E-esc) | 1. Cabozantinib | Not reported |
2. Erlotinib | Superior PFS (primary endpoint) Median PFS: 4.7 vs 1.8 mo (HR 0.37, 80% CI 0.25-0.53) |
Targeted therapy
- Cabozantinib (Cometriq) 40 mg PO once per day
- Erlotinib (Tarceva) 150 mg PO once per day
Continued indefinitely
References
- ECOG-ACRIN 1512: Neal JW, Dahlberg SE, Wakelee HA, Aisner SC, Bowden M, Huang Y, Carbone DP, Gerstner GJ, Lerner RE, Rubin JL, Owonikoko TK, Stella PJ, Steen PD, Khalid AA, Ramalingam SS; ECOG-ACRIN. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial. Lancet Oncol. 2016 Dec;17(12):1661-1671. Epub 2016 Nov 4. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT01708954
Carboplatin & Pemetrexed
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ardizzoni et al. 2012 (GOIRC 02-2006) | 2007-2009 | Randomized Phase 2 (E-esc) | Pemetrexed | Did not meet primary endpoint of PFS |
Chemotherapy
- 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
References
- GOIRC 02-2006: Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00786331
Docetaxel monotherapy
Example orders
Regimen variant #1, 33.3 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gebbia et al. 2008 (DISTAL-2) | 2005-05 to 2006-12 | Phase 3 (C) | 1. Capecitabine & Docetaxel 2a. Docetaxel & Gemcitabine 2b. Docetaxel & Vinorelbine |
Did not meet primary endpoint of OS |
Regimen variant #2, 35 mg/m2, 3 out of 4 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schuette et al. 2005 | 2000-2003 | Phase 3 (E-switch-ic) | Docetaxel; 75 mg/m2, every 3 wks | Might have superior OS |
Garassino et al. 2013 (TAILORNSCLC) | 2007-2012 | Phase 3 (C) | Erlotinib | Seems to have superior OS |
Note: there is another trial named TAILOR in colorectal cancer.
Chemotherapy
- Docetaxel (Taxotere) 35 mg/m2 IV once per day on days 1, 8, 15
Supportive therapy
- Dexamethasone (Decadron) as follows:
- 8 mg PO once per day on days 1, 8, 15; 12 hours prior to docetaxel
- 10 mg IV once per day on days 1, 8, 15; 30 minutes prior to docetaxel
- 8 mg PO once per day on days 1, 8, 15; 12 hours after docetaxel
28-day cycles
Regimen variant #3, 50 mg/m2 q2wk, limited duration
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Pallis et al. 2010 (HORG CT/04.14) | 2004-2008 | Phase 3 (C) | Carboplatin & Docetaxel | Did not meet primary endpoint of OS Median OS: 7.7 vs 10.27 mo |
Prior treatment criteria
- Previous treatment with a platinum-free regimen
Chemotherapy
- Docetaxel (Taxotere) 50 mg/m2 IV once per day on days 1 & 15
28-day cycle for up to 6 cycles
Regimen variant #4, 60 mg/m2 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Takeda et al. 2009 (JCOG 0104) | 2002-01 to 2003-09 | Phase 3 (C) | Docetaxel & Gemcitabine | Did not meet primary endpoint of OS Median OS: 10.1 vs 10.3 mo |
Herbst et al. 2010 (ZODIAC) | 2006-2008 | Phase 3 (C) | Docetaxel & Vandetanib | Inferior PFS |
Kawaguchi et al. 2014 (DELTANSCLC) | 2009-2012 | Phase 3 (C) | Erlotinib | Might have superior PFS |
Garon et al. 2014 (REVEL) | 2010-2013 | Phase 3 (C) | Docetaxel & Ramucirumab | Seems to have inferior OS |
Gridelli et al. 2018 (AvaALL) | 2011-2015 | Phase 3 (C) | Investigator's choice of: 1a. Docetaxel & Bevacizumab 1b. Erlotinib & Bevacizumab 1c. Pemetrexed & Bevacizumab |
Seems to have inferior OS Median OS: 10.2 vs 11.9 mo (HR 1.19, 90% CI 1.00-1.41) |
Note: This is the PMDA-approved dose, the dose used for East Asian patients in REVEL, and the dose used in Japanese patients in EAST-LC. Note that there is another trial named DELTA in indolent lymphoma. While statistically inferior, the median PFS difference in ZODIAC was only 0.8 months.
Prior treatment criteria
- ZODIAC: Platinum-based chemotherapy, with progression
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV over at least 60 minutes once on day 1
21-day cycle for varying durations: 6 cycles (ZODIAC); indefinitely (all others)
Regimen variant #5, 75 mg/m2 q3wk
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Gridelli et al. 2004 (DISTAL 01) | 2000-2002 | Phase 3 (C) | Docetaxel; 33.3 mg/m2, 6 out of 8 wks | Did not meet primary endpoint of QoL | |
Schuette et al. 2005 | 2000-2003 | Phase 3 (C) | Docetaxel; 35 mg/m2, 3 out of 4 wks | Might have inferior OS | |
Paz-Ares et al. 2008 (STELLAR 2) | 2002-2004 | Phase 3 (C) | Paclitaxel poliglumex | Did not meet primary endpoint of OS | |
Krzakowski et al. 2010 | 2003-2005 | Phase 3 (C) | Vinflunine | Non-inferior PFS | |
Herbst et al. 2010 (ZODIAC) | 2006-2008 | Phase 3 (C) | Docetaxel & Vandetanib | Inferior PFS | |
Sun et al. 2012 (JMID) | 2006-2008 | Phase 3 (C) | Pemetrexed | Inconclusive whether non-inferior OS | |
Ciuleanu et al. 2012 (TITAN) | 2006-2010 | Phase 3 (C) | Erlotinib | Did not meet primary endpoint of OS | |
Garassino et al. 2013 (TAILORNSCLC) | 2007-2012 | Phase 3 (C) | Erlotinib | Seems to have superior OS | |
Garon et al. 2014 (REVEL) | 2010-2013 | Phase 3 (C) | Docetaxel & Ramucirumab | Seems to have inferior OS | |
Gridelli et al. 2018 (AvaALL) | 2011-2015 | Phase 3 (C) | Investigator's choice of: 1a. Docetaxel & Bevacizumab 1b. Erlotinib & Bevacizumab 1c. Pemetrexed & Bevacizumab |
Seems to have inferior OS Median OS: 10.2 vs 11.9 mo (HR 1.19, 90% CI 1.00-1.41) |
|
Pillai et al. 2019 (GALAXY-2) | 2013-2015 | Phase 3 (C) | Docetaxel & Ganetespib | Did not meet primary endpoint of OS Median OS: 10.5 vs 10.9 mo (HR 0.90, 95% CI 0.73-1.11) |
Note: while statistically inferior, the median PFS difference in ZODIAC was only 0.8 months.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- Per JMEI: Dexamethasone (Decadron) 8 mg PO twice per day on days -1 to 2 (3 days)
21-day cycle for varying durations: 6 cycles (ZODIAC); indefinitely (all others)
References
- DISTAL 01: Gridelli C, Gallo C, Di Maio M, Barletta E, Illiano A, Maione P, Salvagni S, Piantedosi FV, Palazzolo G, Caffo O, Ceribelli A, Falcone A, Mazzanti P, Brancaccio L, Capuano MA, Isa L, Barbera S, Perrone F. A randomised clinical trial of two docetaxel regimens (weekly vs 3 week) in the second-line treatment of non-small-cell lung cancer: the DISTAL 01 study. Br J Cancer. 2004 Dec 13;91(12):1996-2004. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
- Schuette W, Nagel S, Blankenburg T, Lautenschlaeger C, Hans K, Schmidt EW, Dittrich I, Schweisfurth H, von Weikersthal LF, Raghavachar A, Reissig A, Serke M. Phase III study of second-line chemotherapy for advanced non-small-cell lung cancer with weekly compared with 3-weekly docetaxel. J Clin Oncol. 2005 Nov 20;23(33):8389-95. link to original article dosing details in abstract have been reviewed by our editors PubMed
- STELLAR 2: Paz-Ares L, Ross H, O'Brien M, Riviere A, Gatzemeier U, Von Pawel J, Kaukel E, Freitag L, Digel W, Bischoff H, García-Campelo R, Iannotti N, Reiterer P, Bover I, Prendiville J, Eisenfeld AJ, Oldham FB, Bandstra B, Singer JW, Bonomi P. Phase III trial comparing paclitaxel poliglumex vs docetaxel in the second-line treatment of non-small-cell lung cancer. Br J Cancer. 2008 May 20;98(10):1608-13. Epub 2008 May 13. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed
- DISTAL-2: Gebbia V, Gridelli C, Verusio C, Frontini L, Aitini E, Daniele B, Gamucci T, Mancuso G, Di Maio M, Gallo C, Perrone F, Morabito A. Weekly docetaxel vs docetaxel-based combination chemotherapy as second-line treatment of advanced non-small-cell lung cancer patients: the DISTAL-2 randomized trial. Lung Cancer. 2009 Feb;63(2):251-8. Epub 2008 Jul 15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00345059
- JCOG 0104: Takeda K, Negoro S, Tamura T, Nishiwaki Y, Kudoh S, Yokota S, Matsui K, Semba H, Nakagawa K, Takada Y, Ando M, Shibata T, Saijo N. Phase III trial of docetaxel plus gemcitabine versus docetaxel in second-line treatment for non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG0104). Ann Oncol. 2009 May;20(5):835-41. Epub 2009 Jan 22. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Krzakowski M, Ramlau R, Jassem J, Szczesna A, Zatloukal P, Von Pawel J, Sun X, Bennouna J, Santoro A, Biesma B, Delgado FM, Salhi Y, Vaissiere N, Hansen O, Tan EH, Quoix E, Garrido P, Douillard JY. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol. 2010 May 1;28(13):2167-73. Epub 2010 Mar 29. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ZODIAC: Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00312377
- Dataset: Project Data Sphere
- HORG CT/04.14: Pallis AG, Agelaki S, Agelidou A, Varthalitis I, Syrigos K, Kentepozidis N, Pavlakou G, Kotsakis A, Kontopodis E, Georgoulias V. A randomized phase III study of the docetaxel/carboplatin combination versus docetaxel single-agent as second line treatment for patients with advanced/metastatic non-small cell lung cancer. BMC Cancer. 2010 Nov 19;10:633. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00430651
- TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00556322
- JMID: Sun Y, Wu YL, Zhou CC, Zhang L, Zhang L, Liu XY, Yu SY, Jiang GL, Li K, Qin SK, Ma SL, Han L, Quinlivan M, Orlando M, Zhang XQ. Second-line pemetrexed versus docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer: a randomized, open-label study. Lung Cancer. 2013 Feb;79(2):143-50. Epub 2012 Nov 20. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00391274
- TAILOR: Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00637910
- DELTANSCLC: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- REVEL: Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01168973
- AvaALL: Gridelli C, de Castro Carpeno J, Dingemans AC, Griesinger F, Grossi F, Langer C, Ohe Y, Syrigos K, Thatcher N, Das-Gupta A, Truman M, Donica M, Smoljanovic V, Bennouna J. Safety and Efficacy of Bevacizumab Plus Standard-of-Care Treatment Beyond Disease Progression in Patients With Advanced Non-Small Cell Lung Cancer: The AvaALL Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):e183486. Epub 2018 Dec 13. Erratum in: JAMA Oncol. 2018 Dec 1;4(12):1792. link to original article link to PMC article dosing details in supplement have been reviewed by our editors PubMed NCT01351415
- GALAXY-2: Pillai RN, Fennell DA, Kovcin V, Ciuleanu TE, Ramlau R, Kowalski D, Schenker M, Yalcin I, Teofilovici F, Vukovic VM, Ramalingam SS. Randomized Phase III Study of Ganetespib, a Heat Shock Protein 90 Inhibitor, With Docetaxel Versus Docetaxel in Advanced Non-Small-Cell Lung Cancer (GALAXY-2). J Clin Oncol. 2020 Feb 20;38(6):613-622. Epub 2019 Dec 12. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01798485
- DUBLIN-3: NCT02504489
Docetaxel & Ramucirumab
Regimen variant #1, 60/10
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Garon et al. 2014 (REVEL) | 2010-2013 | Phase 3 (E-RT-esc) | Docetaxel | Seems to have superior OS (primary endpoint) Median OS: 10.5 vs 9.1 mo (HR 0.86, 95% CI 0.75-0.98) |
Note: This is the PMDA-approved dose and the dose recommended for East Asians. The FDA only provides recommendations for ramucirumab dosing.
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
Targeted therapy
- Ramucirumab (Cyramza) 10 mg/kg IV once on day 1
Supportive therapy
- Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.
21-day cycles
Regimen variant #2, 75/10
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Garon et al. 2014 (REVEL) | 2010-2013 | Phase 3 (E-RT-esc) | Docetaxel | Seems to have superior OS (primary endpoint) Median OS: 10.5 vs 9.1 mo (HR 0.86, 95% CI 0.75-0.98) |
Note: The FDA only provides recommendations for ramucirumab dosing.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
Targeted therapy
- Ramucirumab (Cyramza) 10 mg/kg IV once on day 1
Supportive therapy
- Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.
21-day cycles
References
- REVEL: Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. Epub 2014 Jun 2. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01168973
Docetaxel & Vandetanib
Regimen variant #1, 60/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Herbst et al. 2010 (ZODIAC) | 2006-2008 | Phase 3 (E-esc) | Docetaxel | Superior PFS (primary endpoint) Median PFS: 4 vs 3.2 mo (HR 0.79, 97.58% CI 0.70-0.90) |
Note: This is the PMDA-approved dose of docetaxel. While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 up to 6: 60 mg/m2 IV once on day 1
Targeted therapy
- Vandetanib (Caprelsa) 100 mg PO once per day on days 1 to 21
21-day cycles
Regimen variant #2, 75/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Herbst et al. 2010 (ZODIAC) | 2006-2008 | Phase 3 (E-esc) | Docetaxel | Superior PFS (primary endpoint) Median PFS: 4 vs 3.2 mo (HR 0.79, 97.58% CI 0.70-0.90) |
Note: While statistically superior, the median PFS difference was only 0.8 months. Vandetanib is continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Chemotherapy
- Docetaxel (Taxotere) as follows:
- Cycles 1 up to 6: 75 mg/m2 IV once on day 1
Targeted therapy
- Vandetanib (Caprelsa) 100 mg PO once per day on days 1 to 21
21-day cycles
References
- ZODIAC: Herbst RS, Sun Y, Eberhardt WE, Germonpré P, Saijo N, Zhou C, Wang J, Li L, Kabbinavar F, Ichinose Y, Qin S, Zhang L, Biesma B, Heymach JV, Langmuir P, Kennedy SJ, Tada H, Johnson BE. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010 Jul;11(7):619-26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00312377
Gefitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sun et al. 2012 (KCSG-LU08-01) | 2008-2010 | Phase 3 (E-switch-ooc) | Pemetrexed | Superior PFS (primary endpoint) Median PFS: 9 vs 3 mo (HR 0.54, 95% CI 0.37-0.79) |
Note: KCSG-LU08-01 reported 21-day cycles, but other variants of gefitinib use 28-day cycles. There is no practical difference as this drug is taken continuously; the 28-day cycle convention is therefore used, here.
References
- KCSG-LU08-01: Sun JM, Lee KH, Kim SW, Lee DH, Min YJ, Yun HJ, Kim HK, Song HS, Kim YH, Kim BS, Hwang IG, Lee K, Jo SJ, Lee JW, Ahn JS, Park K, Ahn MJ; Korean Cancer Study Group. Gefitinib versus pemetrexed as second-line treatment in patients with nonsmall cell lung cancer previously treated with platinum-based chemotherapy (KCSG-LU08-01): an open-label, phase 3 trial. Cancer. 2012 Dec 15;118(24):6234-42. Epub 2012 Jun 6. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01066195
Gemcitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Crinò et al. 1999a | 1995-11 to 1997-10 | Phase 2 |