Non-small cell lung cancer, Squamous

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Vanderbilt University
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Note: these are regimens tested in histology-specific populations, please see the main NSCLC page for other regimens.

19 regimens on this page
28 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

Chemotherapy

21-day cycle for 4 cycles

References

  1. 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

21-day cycles

References

  1. 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 (GCb)

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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

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

21-day cycles

References

  1. 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
  2. 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 original article link to PMC article contains verified protocol PubMed CTRI/2013/02/003422
  3. 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
  4. 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
  5. ORIENT-12: Zhou C, Wu L, Fan Y, Wang Z, Liu L, Chen G, Zhang L, Huang D, Cang S, Yang Z, Zhou J, Zhou C, Li B, Li J, Fan M, Cui J, Li Y, Zhao H, Fang J, Xue J, Hu C, Sun P, Du Y, Zhou H, Wang S, Zhang W. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol. 2021 Sep;16(9):1501-1511. Epub 2021 May 25. link to original article PubMed NCT03629925

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) 1. CP & Pembrolizumab
2. Carboplatin, nab-Paclitaxel, Pembrolizumab
Inferior OS

Chemotherapy

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

21-day cycle for 6 cycles

References

  1. 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
  2. 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

Immunotherapy

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

Immunotherapy

21-day cycles

References

  1. 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) 1. CP
2. Carboplatin & nab-Paclitaxel
Superior OS
Median OS: 16 mo vs 11 mo
(HR 0.64, 95% CI 0.49-0.85)

Chemotherapy

Immunotherapy

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

References

  1. 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, 5/175

Study Years of enrollment Evidence Comparator Comparative Efficacy
Wang et al. 2021 (BGB-A317-307) 2018-2019 Phase III (C) 1. CP & Tislelizumab
2. Carboplatin, nab-Paclitaxel, Tislelizumab
Inferior PFS

Chemotherapy

21-day cycle for 4 to 6 cycles

Regimen variant #2, 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

21-day cycle for 4 to 6 cycles

Regimen variant #3, 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

Supportive medications

21-day cycle for up to 6 cycles

Regimen variant #4, 6/200 x 4

Study Years of enrollment Evidence Comparator Comparative Efficacy
Paz-Ares et al. 2018 (KEYNOTE-407) 2016-2017 Phase III (C) 1. CP & Pembrolizumab
2. Carboplatin, nab-Paclitaxel, Pembrolizumab
Inferior OS
Paz-Ares et al. 2021 (CheckMate 9LA) 2017-2019 Phase III (C) Carboplatin, Paclitaxel, Ipilimumab, Nivolumab Inferior OS

Chemotherapy

21-day cycle for 4 cycles

Regimen variant #5, 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

21-day cycle for up to 6 cycles

References

  1. 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
  2. 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
  3. KEYNOTE-042: Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. Epub 2019 Apr 4. link to original article PubMed NCT02220894
  4. 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
  5. BGB-A317-307: Wang J, Lu S, Yu X, Hu Y, Sun Y, Wang Z, Zhao J, Yu Y, Hu C, Yang K, Feng G, Ying K, Zhuang W, Zhou J, Wu J, Leaw SJ, Zhang J, Lin X, Liang L, Yang N. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 May 1;7(5):709-717. Epub 2021 Apr 1. link to original article link to PMC article contains verified protocol PubMed NCT03594747
  6. 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

Immunotherapy

Supportive medications

21-day cycle for up to 6 cycles

Subsequent treatment

References

  1. 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-RT-switch-ooc) 1. Carboplatin & Pemetrexed
2. Cisplatin & Pemetrexed
Superior OS

Chemotherapy

Immunotherapy

21-day cycles

References

  1. 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) 1. CP
2. Carboplatin & nab-Paclitaxel
Superior OS
Median OS: 16 mo vs 11 mo
(HR 0.64, 95% CI 0.49-0.85)

Chemotherapy

Immunotherapy

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

References

  1. 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

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

21-day cycle for 4 to 6 cycles

References

  1. 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
  2. 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

21-day cycle for up to 6 cycles

References

  1. 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
    1. Dataset: Project Data Sphere
  2. 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
  3. 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
  4. ORIENT-12: Zhou C, Wu L, Fan Y, Wang Z, Liu L, Chen G, Zhang L, Huang D, Cang S, Yang Z, Zhou J, Zhou C, Li B, Li J, Fan M, Cui J, Li Y, Zhao H, Fang J, Xue J, Hu C, Sun P, Du Y, Zhou H, Wang S, Zhang W. Sintilimab Plus Platinum and Gemcitabine as First-Line Treatment for Advanced or Metastatic Squamous NSCLC: Results From a Randomized, Double-Blind, Phase 3 Trial (ORIENT-12). J Thorac Oncol. 2021 Sep;16(9):1501-1511. Epub 2021 May 25. link to original article PubMed NCT03629925

Cisplatin & Gemcitabine (GC) & 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

Targeted therapy

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 cycles

References

  1. 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
    1. 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

21-day cycle for 4 to 6 cycles

References

  1. 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
  2. 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

12-week cycles

References

  1. 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

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

21-day cycles

References

  1. 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

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

Continued indefinitely

References

  1. 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

21-day cycles

References

  1. 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
    1. 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
    2. 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
    3. 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
Median OS: 9 mo vs 6 mo
(HR 0.59, 95% CI 0.44-0.79)

Immunotherapy

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

14-day cycles

References

  1. CheckMate 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
  2. 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
    1. 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
    2. 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
    3. 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
  3. Lung-MAP: NCT02785952