Difference between revisions of "Non-small cell lung cancer, squamous"
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| style="background-color:#1a9851" |Phase III (C) | | style="background-color:#1a9851" |Phase III (C) | ||
− | |[[# | + | |[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Necitumumab|Cisplatin, Gemcitabine, Necitumumab]] |
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
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====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[# | + | *[[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Necitumumab|Cisplatin, Gemcitabine, Necitumumab]] x 6 |
====Targeted therapy==== | ====Targeted therapy==== |
Revision as of 00:52, 27 April 2021
Page editor | Section editor | ||
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Amit Kulkarni, MBBS University of Minnesota Minneapolis, MN AmitKulkarniMD |
Travis Osterman, DO, MS, FAMIA Vanderbilt University Nashville, TN TravisOsterman |
Note: these are regimens tested in histology-specific populations, please see the main NSCLC page for other regimens.
40 regimens on this page
57 variants on this page
|
Adjuvant therapy
Cisplatin & Gemcitabine (GC)
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GC: Gemcitabine & Cisplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Groen et al. 2019 (NVALT-8) | 2007-2013 | Phase III (C) | GC & Nadroparin | Did not meet primary endpoint of RFS |
Preceding treatment
- Complete R0 resection, within 6 weeks
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 4 cycles
References
- NVALT-8: Groen HJM, van der Heijden EHFM, Klinkenberg TJ, Biesma B, Aerts J, Verhagen A, Kloosterziel C, Pieterman R, van den Borne B, Smit HJM, Hoekstra O, Schramel FMNH, van der Noort V, van Tinteren H, Smit EF, Dingemans AC; NVALT Study Group. Randomised phase 3 study of adjuvant chemotherapy with or without nadroparin in patients with completely resected non-small-cell lung cancer: the NVALT-8 study. Br J Cancer. 2019 Aug;121(5):372-377. Epub 2019 Jul 24. link to original article contains verified protocol PubMed NTR1250/1217
Advanced or metastatic disease, first-line
Atezolizumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Herbst et al. 2020 (IMpower110) | 2015-2018 | Phase III (E-switch-ooc) | 1. Carboplatin & Gemcitabine 2. Cisplatin & Gemcitabine |
Superior OS1 (HR 0.59, 95% CI 0.40-0.89) |
1Reported efficacy for IMpower110 is for TC3/IC3 only i.e., PD-L1 TC>50%.
Biomarker eligibility criteria
- PD-L1 expression on at least 1% of tumor cells or tumor-infiltrating immune cells covering at least 1% of the tumor area as determined by the SP142 assay
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMpower110: Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. link to original article contains verified protocol PubMed NCT02409342
Carboplatin & Gemcitabine
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Regimen variant #1, 5/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Patil et al. 2019 | 2013-2018 | Phase III (C) | GCb; low-dose Gemcitabine | Non-inferior OS |
Herbst et al. 2020 (IMpower110) | 2015-2018 | Phase III (C) | Atezolizumab | Inferior OS1 |
1Reported efficacy for IMpower110 is for TC3/IC3 only i.e., PD-L1 TC>50%.
Note: CrCl in Patil et al. 2019 was calculated using Cockcroft–Gault.
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
21-day cycle for up to 6 cycles
Regimen variant #2, 5.5/1000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Edelman et al. 2017 (CALGB 30801) | 2010-2013 | Phase III (C) | GCb & Celecoxib | Did not meet primary endpoint of PFS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 5.5 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
21-day cycles
References
- CALGB 30801: Edelman MJ, Wang X, Hodgson L, Cheney RT, Baggstrom MQ, Thomas SP, Gajra A, Bertino E, Reckamp KL, Molina J, Schiller JH, Mitchell-Richards K, Friedman PN, Ritter J, Milne G, Hahn OM, Stinchcombe TE, Vokes EE; Alliance for Clinical Trials in Oncology. Phase III randomized, placebo-controlled, double-blind trial of celecoxib in addition to standard chemotherapy for advanced non-small-cell lung cancer with cyclooxygenase-2 overexpression: CALGB 30801 (Alliance). J Clin Oncol. 2017 Jul 1;35(19):2184-2192. Epub 2017 May 10. link to original article link to PMC article contains verified protocol PubMed NCT01041781
- Patil V, Noronha V, Joshi A, Chougule A, Kannan S, Bhattacharjee A, Goud S, More S, Chandrasekharan A, Menon N, Srinivas S, Vallathol DH, Dsouza H, Majumdar S, Das S, Zawar A, Khaddar S, Kumar A, Singh G, Kumar KAP, Ravind R, Trivedi V, Behel V, Mahajan A, Janu A, Purandare N, Prabhash K. Phase III non-inferiority study evaluating efficacy and safety of low dose gemcitabine compared to standard dose gemcitabine with platinum in advanced squamous lung cancer. EClinicalMedicine. 2019 Apr 9;9:19-25. link to PMC article contains verified protocol PubMed CTRI/2013/02/003422
- 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 link to PMC article PubMed NCT02453282
- IMpower110: Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. link to original article contains verified protocol PubMed NCT02409342
Carboplatin & nab-Paclitaxel
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CnP: Carboplatin & nab-Paclitaxel
Regimen variant #1, 4 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jotte et al. 2020 (IMpower131) | 2015-2017 | Phase III (C) | 1. A+CnP x 4, then Atezolizumab maintenance | Inferior PFS |
2. A+CP x 4, then Atezolizumab maintenance | Not reported | |||
Paz-Ares et al. 2018 (KEYNOTE-407) | 2016-2017 | Phase III (C) | Carboplatin, nab-Paclitaxel, Pembrolizumab x 4, then Pembrolizumab maint. | Inferior OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 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 cycles
Regimen variant #2, 6 cycles
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jotte et al. 2020 (IMpower131) | 2015-2017 | Phase III (C) | 1. A+CnP x 6, then Atezolizumab maintenance | Inferior PFS |
2. A+CP x 6, then Atezolizumab maintenance | Not reported |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 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 6 cycles
References
- KEYNOTE-407: Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. link to original article contains verified protocol PubMed NCT02775435
- IMpower131: Jotte R, Cappuzzo F, Vynnychenko I, Stroyakovskiy D, Rodríguez-Abreu D, Hussein M, Soo R, Conter HJ, Kozuki T, Huang KC, Graupner V, Sun SW, Hoang T, Jessop H, McCleland M, Ballinger M, Sandler A, Socinski MA. Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial. J Thorac Oncol. 2020 Aug;15(8):1351-1360. Epub 2020 Apr 14. link to original article contains verified protocol PubMed NCT02367794
Carboplatin, nab-Paclitaxel, Atezolizumab
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A+CnP: Atezolizumab, Carboplatin, nab-Paclitaxel
Regimen variant #1, 4 cycles of CnP
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jotte et al. 2020 (IMpower131) | 2015-2017 | Phase III (E-esc) | 1. CnP x 4 | Superior PFS |
2. A+CP x 4, then Atezolizumab maintenance | Not reported |
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
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
Regimen variant #2, 6 cycles of CnP
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Jotte et al. 2020 (IMpower131) | 2015-2017 | Phase III (E-esc) | 1. CnP x 6 | Superior PFS |
2. A+CP x 6, then Atezolizumab maintenance | Not reported |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 to 6: AUC 6 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
- Cycles 1 to 6: 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMpower131: Jotte R, Cappuzzo F, Vynnychenko I, Stroyakovskiy D, Rodríguez-Abreu D, Hussein M, Soo R, Conter HJ, Kozuki T, Huang KC, Graupner V, Sun SW, Hoang T, Jessop H, McCleland M, Ballinger M, Sandler A, Socinski MA. Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial. J Thorac Oncol. 2020 Aug;15(8):1351-1360. Epub 2020 Apr 14. link to original article contains verified protocol PubMed NCT02367794
Carboplatin, nab-Paclitaxel, Pembrolizumab
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2018 (KEYNOTE-407) | 2016-2017 | Phase III (E-RT-esc) | See link | See link |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV once per day on days 1, 8, 15
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1, given first
21-day cycle for 4 cycles
Subsequent treatment
References
- KEYNOTE-407: Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. link to original article contains verified protocol PubMed NCT02775435
Carboplatin & Paclitaxel (CP)
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TC: Taxol (Paclitaxel) & Carboplatin
CP: Carboplatin & Paclitaxel
Regimen variant #1, 5/200
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Phase III (C) | Pembrolizumab | Inferior OS |
Patients enrolled in this arm of KEYNOTE-042 had squamous histology.
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 4 to 6 cycles
Regimen variant #2, 6/175
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Govindan et al. 2017 (CA184-104) | 2011-2015 | Phase III (C) | TC & Ipilimumab | Did not meet primary endpoint of OS |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
Supportive medications
- Corticosteroids could be used as premedication for Paclitaxel (Taxol) infusion.
21-day cycle for up to 6 cycles
Regimen variant #3, 6/200 x 4
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2018 (KEYNOTE-407) | 2016-2017 | Phase III (C) | CP & Pembrolizumab x 4, then Pembrolizumab maint. | Inferior OS |
Paz-Ares et al. 2021 (CheckMate 9LA) | 2017-2019 | Phase III (C) | Carboplatin, Paclitaxel, Ipilimumab, Nivolumab | Inferior OS |
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 4 cycles
Regimen variant #4, 6/200 x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mok et al. 2019 (KEYNOTE-042) | 2014-2017 | Phase III (C) | Pembrolizumab | Inferior OS |
Patients enrolled in this arm of KEYNOTE-042 had squamous histology.
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 6 cycles
References
- CA184-104: Govindan R, Szczesna A, Ahn MJ, Schneider CP, Gonzalez Mella PF, Barlesi F, Han B, Ganea DE, Von Pawel J, Vladimirov V, Fadeeva N, Lee KH, Kurata T, Zhang L, Tamura T, Postmus PE, Jassem J, O'Byrne K, Kopit J, Li M, Tschaika M, Reck M. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017 Oct 20;35(30):3449-3457. Epub 2017 Aug 30. link to original article contains verified protocol PubMed NCT01285609
- KEYNOTE-407: Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. link to original article contains verified protocol PubMed NCT02775435
- 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
- CheckMate 9LA: Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, Richardet E, Bennouna J, Felip E, Juan-Vidal O, Alexandru A, Sakai H, Lingua A, Salman P, Souquet PJ, De Marchi P, Martin C, Pérol M, Scherpereel A, Lu S, John T, Carbone DP, Meadows-Shropshire S, Agrawal S, Oukessou A, Yan J, Reck M. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198-211. Epub 2021 Jan 18. link to original article contains verified protocol PubMed NCT03215706
- M11-089: NCT02106546
Carboplatin & Paclitaxel (CP) & Ipilimumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Govindan et al. 2017 (CA184-104) | 2011-2015 | Phase III (E-esc) | Carboplatin & Paclitaxel | Did not meet primary endpoint of OS |
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 medications
- Corticosteroids could be used as premedication for Paclitaxel (Taxol) infusion or for toxicity management.
21-day cycle for up to 6 cycles
Subsequent treatment
References
- CA184-104: Govindan R, Szczesna A, Ahn MJ, Schneider CP, Gonzalez Mella PF, Barlesi F, Han B, Ganea DE, Von Pawel J, Vladimirov V, Fadeeva N, Lee KH, Kurata T, Zhang L, Tamura T, Postmus PE, Jassem J, O'Byrne K, Kopit J, Li M, Tschaika M, Reck M. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017 Oct 20;35(30):3449-3457. Epub 2017 Aug 30. link to original article contains verified protocol PubMed NCT01285609
Carboplatin & Paclitaxel (CP) & Ipilimumab, Nivolumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2021 (CheckMate 9LA) | 2017-2019 | Phase III (E-switch-ooc) | 1. Carboplatin & Pemetrexed 2. Cisplatin & Pemetrexed |
Superior OS |
Chemotherapy
- Carboplatin (Paraplatin) as follows:
- Cycles 1 & 2: AUC 6 IV once on day 1
- Paclitaxel (Taxol) as follows:
- Cycles 1 & 2: 200 mg/m2 IV once on day 1
Immunotherapy
- Ipilimumab (Yervoy) as follows:
- Odd cycles: 1 mg/kg IV once on day 1
- Nivolumab (Opdivo) 360 mg IV once on day 1, given first
21-day cycles
References
- CheckMate 9LA: Paz-Ares L, Ciuleanu TE, Cobo M, Schenker M, Zurawski B, Menezes J, Richardet E, Bennouna J, Felip E, Juan-Vidal O, Alexandru A, Sakai H, Lingua A, Salman P, Souquet PJ, De Marchi P, Martin C, Pérol M, Scherpereel A, Lu S, John T, Carbone DP, Meadows-Shropshire S, Agrawal S, Oukessou A, Yan J, Reck M. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198-211. Epub 2021 Jan 18. link to original article contains verified protocol PubMed NCT03215706
Carboplatin & Paclitaxel (CP) & Pembrolizumab
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2018 (KEYNOTE-407) | 2016-2017 | Phase III (E-RT-esc) | See link | See link |
Chemotherapy
- Carboplatin (Paraplatin) AUC 6 IV once on day 1
- Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1, given first
21-day cycle for 4 cycles
Subsequent treatment
References
- KEYNOTE-407: Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. link to original article contains verified protocol PubMed NCT02775435
Cisplatin & Docetaxel (DC)
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DC: Docetaxel & Cisplatin
CD: Cisplatin & Docetaxel
Regimen variant #1, 75/75
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lu et al. 2018 (5501068) | 2013-2015 | Phase III (C) | Docetaxel & Nedaplatin | Might have inferior PFS |
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 4 cycles
Regimen variant #2, 80/60
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shukuya et al. 2015 (WJOG5208L) | 2009-2012 | Phase III (C) | Docetaxel & Nedaplatin | Seems to have inferior OS |
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
21-day cycle for 4 to 6 cycles
References
- WJOG5208L: Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, Sugawara S, Takahashi T, Yokota S, Kaneda H, Kawaguchi T, Nagase S, Oguri T, Iwamoto Y, Nishimura T, Hattori Y, Nakagawa K, Nakanishi Y, Yamamoto N; West Japan Oncology Group. Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1630-8. Epub 2015 Oct 28. link to original article contains protocol PubMed UMIN000002015
- 5501068: Lu S, Chen Z, Hu C, Zhang J, Chen Y, Song Y, Zhao Q, Fan Y, Wu G, Ma Z, Fang J, Yu Q, Liu Z. Nedaplatin plus docetaxel versus cisplatin plus docetaxel as first-line chemotherapy for advanced squamous cell carcinoma of the lung - a multicenter, open-label, randomized, phase III trial. J Thorac Oncol. 2018 Nov;13(11):1743-1749. Epub 2018 Jul 11. link to original article contains verified protocol PubMed NCT02088515
Cisplatin & Gemcitabine (GC)
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GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2015 (SQUIRE) | 2010-2012 | Phase III (C) | Cisplatin, Gemcitabine, Necitumumab | Seems to have inferior OS |
Herbst et al. 2020 (IMpower110) | 2015-2018 | Phase III (C) | Atezolizumab | Inferior OS1 |
1Reported efficacy for IMpower110 is for TC3/IC3 only i.e., PD-L1 TC>50%.
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 2 hours once per day on days 1 & 8
21-day cycle for up to 6 cycles
References
- SQUIRE: Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. Epub 2015 Jun 1. link to original article contains protocol PubMed NCT00981058
- Dataset: Project Data Sphere
- 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 link to PMC article PubMed NCT02453282
- IMpower110: Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Özgüroğlu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. link to original article contains verified protocol PubMed NCT02409342
Cisplatin, Gemcitabine, Necitumumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Thatcher et al. 2015 (SQUIRE) | 2010-2012 | Phase III (E-RT-esc) | Cisplatin & Gemcitabine | Seems to have superior OS |
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1
- Gemcitabine (Gemzar) 1250 mg/m2 IV over 30 minutes once per day on days 1 & 8
Targeted therapy
- Necitumumab (Portrazza) 800 mg IV over at least 50 minutes once per day on days 1 & 8
Supportive medications
- Antiemetic premedications for gemcitabine and cisplatin "according to local practice."
- "Pre-emptive treatment for skin toxicity was allowed only after the first cycle."
21-day cycle for 6 cycles
Subsequent treatment
References
- SQUIRE: Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. Epub 2015 Jun 1. link to original article contains verified protocol PubMed NCT00981058
- Dataset: Project Data Sphere
Docetaxel & Nedaplatin
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shukuya et al. 2015 (WJOG5208L) | 2009-2012 | Phase III (E-switch-ic) | Cisplatin & Docetaxel | Seems to have superior OS |
Chemotherapy
- Docetaxel (Taxotere) 60 mg/m2 IV once on day 1
- Nedaplatin (Aqupla) 100 mg/m2 IV once on day 1
21-day cycle for 4 to 6 cycles
References
- WJOG5208L: Shukuya T, Yamanaka T, Seto T, Daga H, Goto K, Saka H, Sugawara S, Takahashi T, Yokota S, Kaneda H, Kawaguchi T, Nagase S, Oguri T, Iwamoto Y, Nishimura T, Hattori Y, Nakagawa K, Nakanishi Y, Yamamoto N; West Japan Oncology Group. Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1630-8. Epub 2015 Oct 28. link to original article contains protocol PubMed UMIN000002015
- 5501068: Lu S, Chen Z, Hu C, Zhang J, Chen Y, Song Y, Zhao Q, Fan Y, Wu G, Ma Z, Fang J, Yu Q, Liu Z. Nedaplatin plus docetaxel versus cisplatin plus docetaxel as first-line chemotherapy for advanced squamous cell carcinoma of the lung - a multicenter, open-label, randomized, phase III trial. J Thorac Oncol. 2018 Nov;13(11):1743-1749. Epub 2018 Jul 11. link to original article contains verified protocol PubMed NCT02088515
Maintenance after first-line therapy
Ipilimumab monotherapy
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Regimen
Study | Evidence |
---|---|
Govindan et al. 2017 (CA184-104) | Non-randomized portion of RCT |
Preceding treatment
Immunotherapy
- Ipilimumab (Yervoy) 10 mg/kg IV once on day 1
12-week cycles
References
- CA184-104: Govindan R, Szczesna A, Ahn MJ, Schneider CP, Gonzalez Mella PF, Barlesi F, Han B, Ganea DE, Von Pawel J, Vladimirov V, Fadeeva N, Lee KH, Kurata T, Zhang L, Tamura T, Postmus PE, Jassem J, O'Byrne K, Kopit J, Li M, Tschaika M, Reck M. Phase III trial of ipilimumab combined with paclitaxel and carboplatin in advanced squamous non-small-cell lung cancer. J Clin Oncol. 2017 Oct 20;35(30):3449-3457. Epub 2017 Aug 30. link to original article contains verified protocol PubMed NCT01285609
Necitumumab monotherapy
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Regimen
Study | Evidence |
---|---|
Thatcher et al. 2015 (SQUIRE) | Non-randomized portion of RCT |
Patients had stage IV squamous non-small-cell lung cancer.
Preceding treatment
Targeted therapy
- Necitumumab (Portrazza) 800 mg IV over at least 50 minutes once per day on days 1 & 8
21-day cycles
References
- SQUIRE: Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. Epub 2015 Jun 1. link to original article contains verified protocol PubMed NCT00981058
- Dataset: Project Data Sphere
Pembrolizumab monotherapy
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Paz-Ares et al. 2018 (KEYNOTE-407) | 2016-2017 | Phase III (E-RT-esc) | See link | See link |
Preceding treatment
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (including induction)
References
- KEYNOTE-407: Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gümüş M, Mazières J, Hermes B, Çay Şenler F, Csőszi T, Fülöp A, Rodríguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. Epub 2018 Sep 25. link to original article contains verified protocol PubMed NCT02775435
S-1 monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tanaka et al. 2020 (WJOG7512L) | 2013-2017 | Phase III (E-esc) | Observation | Superior PFS |
Preceding treatment
- Carboplatin & S-1 induction
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) 40 mg/m2 PO twice per day on days 1 to 14
21-day cycles
References
- WJOG7512L: Tanaka K, Morita S, Ando M, Yokoyama T, Nakamura A, Yoshioka H, Ishiguro T, Miura S, Toyozawa R, Oguri T, Daga H, Ko R, Bessho A, Tachihara M, Iwamoto Y, Hirano K, Nakanishi Y, Nakagawa K, Yamamoto N, Okamoto I. A randomized phase 3 study of maintenance therapy with S-1 plus best supportive care versus best supportive care after induction therapy with carboplatin plus S-1 for advanced or relapsed squamous cell carcinoma of the lung (WJOG7512L). Cancer. 2020 Aug 15;126(16):3648-3656. Epub 2020 Jun 2. link to original article contains verified protocol PubMed UMIN000010396
Advanced or metastatic disease, second-line
Afatinib monotherapy
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Regimen variant #1, 30 mg/day
FDA-recommended dose |
This is the FDA-recommended dose for patients with "severe renal impairment".
Targeted therapy
- Afatinib (Gilotrif) 30 mg PO once per day
Continued indefinitely
Regimen variant #2, 40 mg/day
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soria et al. 2015 (LUX-Lung 8) | 2012-2014 | Phase III (E-RT-switch-ic) | Erlotinib | Superior OS |
Targeted therapy
- Afatinib (Gilotrif) 40 mg PO once per day, given 1 hour before eating food
Continued indefinitely
References
- LUX-Lung 8: Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. link to original article contains protocol PubMed NCT01523587
Advanced or metastatic disease, subsequent lines of therapy
Note: this section includes regimens that were tested in second-line and beyond.
Docetaxel monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Brahmer et al. 2015 (CheckMate 017) | 2012-2013 | Phase III (C) | Nivolumab | Inferior OS |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycles
References
- CheckMate 017: Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. link to original article link to PMC article PubMed NCT01642004
- Pooled update: Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhäeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crinò L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec 10;35(35):3924-3933. Epub 2017 Oct 12. link to original article PubMed
- HRQoL analysis: Reck M, Taylor F, Penrod JR, DeRosa M, Morrissey L, Dastani H, Orsini L, Gralla RJ. Impact of nivolumab versus docetaxel on health-related quality of life and symptoms in patients with advanced squamous non-small cell lung cancer: results from the CheckMate 017 study. J Thorac Oncol. 2018 Feb;13(2):194-204. Epub 2017 Nov 10. link to original article PubMed
- Pooled update: Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wójcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, García MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Mar 1;39(7):723-733. Epub 2021 Jan 15. link to original article PubMed
Nivolumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rizvi et al. 2015 (CheckMate 063) | 2012-2013 | Phase II | ||
Brahmer et al. 2015 (CheckMate 017) | 2012-2013 | Phase III (E-RT-switch-ooc) | Docetaxel | Superior OS |
Immunotherapy
- Nivolumab (Opdivo) 3 mg/kg IV once on day 1
- Notably, on 9/13/16 the FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.
14-day cycles
References
- CheckMate 063: Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Feb 19. link to original article contains verified protocol PubMed NCT01721759
- CheckMate 017: Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. link to original article link to PMC article PubMed NCT01642004
- Pooled update: Horn L, Spigel DR, Vokes EE, Holgado E, Ready N, Steins M, Poddubskaya E, Borghaei H, Felip E, Paz-Ares L, Pluzanski A, Reckamp KL, Burgio MA, Kohlhäeufl M, Waterhouse D, Barlesi F, Antonia S, Arrieta O, Fayette J, Crinò L, Rizvi N, Reck M, Hellmann MD, Geese WJ, Li A, Blackwood-Chirchir A, Healey D, Brahmer J, Eberhardt WEE. Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer: two-year outcomes from two randomized, open-label, phase III trials (CheckMate 017 and CheckMate 057). J Clin Oncol. 2017 Dec 10;35(35):3924-3933. Epub 2017 Oct 12. link to original article PubMed
- HRQoL analysis: Reck M, Taylor F, Penrod JR, DeRosa M, Morrissey L, Dastani H, Orsini L, Gralla RJ. Impact of nivolumab versus docetaxel on health-related quality of life and symptoms in patients with advanced squamous non-small cell lung cancer: results from the CheckMate 017 study. J Thorac Oncol. 2018 Feb;13(2):194-204. Epub 2017 Nov 10. link to original article PubMed
- Pooled update: Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wójcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, García MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Mar 1;39(7):723-733. Epub 2021 Jan 15. link to original article PubMed