Non-small cell lung cancer, squamous

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Note: these are regimens tested in histology-specific populations, please see the main NSCLC page for other regimens 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!.
Last updated on 2024-12-02:42 regimens on this page
56 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ESMO==
*2023: Hendriks et al. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Non-Small Cell Lung Cancer.
=Perioperative therapy=
==Carboplatin & Gemcitabine (GCb) & Durvalumab==
GCb & Durvalumab: Gemcitabine, Carboplatin, Durvalumab
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heymach et al. 2023 (AEGEAN)	2019-01-02 to 2022-04-19	Phase 3 (E-RT-esc)	1a. CP1b. GC1c. GCb	Longer EFS (co-primary endpoint)EFS12: 73.4% vs 64.5%(sHR 0.68, 95% CI 0.53-0.88)
 	 	Phase 3 (E-RT-esc)	 	
===Neoadjuvant===
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
28-day cycle for up to 12 cycles
===References===
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
==Carboplatin & Paclitaxel (CP) & Durvalumab==
CP & Durvalumab: Carboplatin, Paclitaxel, Durvalumab
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heymach et al. 2023 (AEGEAN)	2019-01-02 to 2022-04-19	Phase 3 (E-RT-esc)	1a. CP1b. GC1c. GCb	Longer EFS (co-primary endpoint)EFS12: 73.4% vs 64.5%(sHR 0.68, 95% CI 0.53-0.88)
 	 	Phase 3 (E-RT-esc)	 	
===Neoadjuvant===
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
28-day cycle for up to 12 cycles
===References===
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
==Carboplatin & Paclitaxel (CP) & Nivolumab==
CP & Nivolumab: Carboplatin, Paclitaxel, Nivolumab
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cascone et al. 2024 (CheckMate 77T)	2019-11 to 2022-04 	Phase 3 (E-RT-esc)	1a. DC1b. CP	Longer EFS (primary endpoint)EFS18: 70.2% vs 50%(HR 0.58, 97.36% CI 0.42-0.81)
===Neoadjuvant===
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Paclitaxel (Taxol) 175 or 200 mg/m2 IV once on day 1
====Immunotherapy====
*Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Nivolumab (Opdivo) 480 mg IV once on day 1
28-day cycle for 13 cycles (1 year)
===References===
#CheckMate 77T: Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024 May 16;390(19):1756-1769. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT04025879
==Cisplatin & Docetaxel (DC) & Nivolumab==
DC & Nivolumab: Docetaxel, Cisplatin, Nivolumab
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cascone et al. 2024 (CheckMate 77T)	2019-11 to 2022-04 	Phase 3 (E-RT-esc)	1a. DC1b. CP	Longer EFS (primary endpoint)EFS18: 70.2% vs 50%(HR 0.58, 97.36% CI 0.42-0.81)
===Neoadjuvant===
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
====Immunotherapy====
*Nivolumab (Opdivo) 360 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Nivolumab (Opdivo) 480 mg IV once on day 1
28-day cycle for 13 cycles (1 year)
===References===
#CheckMate 77T: Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024 May 16;390(19):1756-1769. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT04025879
==Cisplatin & Gemcitabine (GC) & Durvalumab==
GC & Durvalumab: Gemcitabine, Cisplatin, Durvalumab
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heymach et al. 2023 (AEGEAN)	2019-01-02 to 2022-04-19	Phase 3 (E-RT-esc)	1a. CP1b. GC1c. GCb	Longer EFS (co-primary endpoint)EFS12: 73.4% vs 64.5%(sHR 0.68, 95% CI 0.53-0.88)
 	 	Phase 3 (E-RT-esc)	 	
===Neoadjuvant===
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Durvalumab (Imfinzi) 1500 mg IV once on day 1
28-day cycle for up to 12 cycles
===References===
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
==Cisplatin & Gemcitabine (GC) & Pembrolizumab==
GC & Pembrolizumab: Gemcitabine, Cisplatin, Pembrolizumab
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wakelee et al. 2023 (KEYNOTE-671)	2018-04 to 2021-12 	Phase 3 (E-esc)	GC 	Longer OS1 (co-primary endpoint)OS36: 71% vs 64%(HR 0.72, 95% CI 0.56-0.93)Longer EFS1 (co-primary endpoint)Median EFS: 47.2 vs 18.3 mo(HR 0.59, 95% CI 0.48-0.72)
1Reported efficacy is based on the 2024 update.
===Neoadjuvant===
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for 4 cycles
===Definitive===
====Local therapy====
*Complete resection
===Adjuvant===
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 13 cycles
===References===
#KEYNOTE-671: Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. Epub 2023 Jun 3. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT03425643
##Update: Spicer JD, Garassino MC, Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novello S, Yang J, Arunachalam A, Keller SM, Samkari A, Gao S; KEYNOTE-671 Investigators. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2024 Sep 28;404(10459):1240-1252. Epub 2024 Sep 14. link to original article EuroPMC
=Neoadjuvant therapy=
==Carboplatin & Gemcitabine (GCb)==
GCb: Gemcitabine & Carboplatin
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heymach et al. 2023 (AEGEAN)	2019-01-02 to 2022-04-19	Phase 3 (C)	1a. CP & Durvalumab1b. GC & Durvalumab1c. GCb & Durvalumab	Shorter EFS (co-primary endpoint)EFS12: 64.5% vs 73.4%(sHR 1.47, 95% CI 1.14-1.89)
 	 	Phase 3 (C)	 	
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Complete resection
===References===
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
==Carboplatin & Paclitaxel (CP)==
CP: Carboplatin & Paclitaxel
===Regimen variant #1, 6/200===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Heymach et al. 2023 (AEGEAN)	2019-01-02 to 2022-04-19	Phase 3 (C)	1a. CP & Durvalumab1b. GC & Durvalumab1c. GCb & Durvalumab	Shorter EFS (co-primary endpoint)EFS12: 64.5% vs 73.4%(sHR 1.47, 95% CI 1.14-1.89)
 	 	Phase 3 (C)	 	
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm; this was the upper bound of dosing in CheckMate 77T.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 200 mg/m2 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Complete resection
===Regimen variant #2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cascone et al. 2024 (CheckMate 77T)	2019-11 to 2022-04 	Phase 3 (C)	1a. DC & Nivolumab1b. CP & Nivolumab	Shorter EFSEFS18: 50% vs 70.2%(HR 1.72, 97.36% CI 1.23-2.38)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
*Paclitaxel (Taxol) 175 or 200 mg/m2 IV once on day 1
21-day cycle for 4 cycles
====Subsequent treatment====
*Complete resection
===References===
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
#CheckMate 77T: Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024 May 16;390(19):1756-1769. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT04025879
==Cisplatin & Docetaxel (DC)==
DC: Docetaxel & Cisplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cascone et al. 2024 (CheckMate 77T)	2019-11 to 2022-04 	Phase 3 (C)	1a. DC & Nivolumab1b. CP & Nivolumab	Shorter EFSEFS18: 50% vs 70.2%(HR 1.72, 97.36% CI 1.23-2.38)
====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
====Subsequent treatment====
*Complete resection
===References===
#CheckMate 77T: Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, Karaseva N, Kuzdzal J, Petruzelka LB, Wu L, Pujol JL, Ito H, Ciuleanu TE, de Oliveira Muniz Koch L, Janssens A, Alexandru A, Bohnet S, Moiseyenko FV, Gao Y, Watanabe Y, Coronado Erdmann C, Sathyanarayana P, Meadows-Shropshire S, Blum SI, Provencio Pulla M; CheckMate 77T Investigators. Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med. 2024 May 16;390(19):1756-1769. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT04025879
==Cisplatin & Gemcitabine (GC)==
GC: Gemcitabine & Cisplatin
===Regimen variant #1, 1000/75===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019 	Phase 3 (C)	1a. CP & Nivolumab1b. CVb & Nivolumab1c. DC & Nivolumab1d. GC & Nivolumab	Shorter EFSMedian EFS: 20.8 vs 31.6 mo(HR 1.59, 97.38% CI 1.10-2.33)Lower pCR ratepCR rate: 2.2% vs 24%(OR 0.07, 99% CI 0.02-0.29)
Wakelee et al. 2023 (KEYNOTE-671)	2018-04 to 2021-12 	Phase 3 (C)	GC & Pembrolizumab 	Shorter OS1 (co-primary endpoint)OS36: 64% vs 71%(HR 1.39, 95% CI 1.08-1.79)Shorter EFS1 (co-primary endpoint)Median EFS: 18.3 vs 47.2 mo(HR 1.69, 95% CI 1.39-2.08)
1Reported efficacy for KEYNOTE-671 is based on the 2024 update.
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Biomarker eligibility criteria====
*CheckMate 816: No sensitizing EGFR or ALK mutations
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
21-day cycle for varying durations: 3 cycles (CheckMate 816); 4 cycles (KEYNOTE-671)
====Subsequent treatment====
*Complete resection
===Regimen variant #2, 1250/75===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019 	Phase 3 (C)	1a. CP & Nivolumab1b. CVb & Nivolumab1c. DC & Nivolumab1d. GC & Nivolumab	Shorter EFSMedian EFS: 20.8 vs 31.6 mo(HR 1.59, 97.38% CI 1.10-2.33)Lower pCR ratepCR rate: 2.2% vs 24%(OR 0.07, 99% CI 0.02-0.29)
Heymach et al. 2023 (AEGEAN) 	2019-01-02 to 2022-04-19	Phase 3 (C)	1a. CP & Durvalumab1b. GC & Durvalumab1c. GCb & Durvalumab 	Shorter EFS (co-primary endpoint)EFS12: 64.5% vs 73.4%(sHR 1.47, 95% CI 1.14-1.89)
 	 	Phase 3 (C)	 	
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.
====Biomarker eligibility criteria====
*CheckMate 816: No sensitizing EGFR or ALK mutations
====Chemotherapy====
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
21-day cycle for varying durations: 3 cycles (CheckMate 816); 4 cycles (AEGEAN)
====Subsequent treatment====
*Complete resection
===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 EuroPMC NCT02998528
#KEYNOTE-671: Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodríguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. Epub 2023 Jun 3. link to original article dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT03425643
#AEGEAN: Heymach JV, Harpole D, Mitsudomi T, Taube JM, Galffy G, Hochmair M, Winder T, Zukov R, Garbaos G, Gao S, Kuroda H, Ostoros G, Tran TV, You J, Lee KY, Antonuzzo L, Papai-Szekely Z, Akamatsu H, Biswas B, Spira A, Crawford J, Le HT, Aperghis M, Doherty GJ, Mann H, Fouad TM, Reck M; AEGEAN Investigators. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 2;389(18):1672-1684. Epub 2023 Oct 23. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03800134
==Cisplatin & Gemcitabine (GC) & Nivolumab==
GC & Nivolumab: Gemcitabine, Cisplatin, Nivolumab
===Regimen variant #1, 1000/75/360===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019 	Phase 3 (E-RT-esc)	1a. CP1b. CVb1c. DC1d. GC	Longer EFS (co-primary endpoint)Median EFS: 31.6 vs 20.8 mo(HR 0.63, 97.38% CI 0.43-0.91)Higher 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====
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
*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====
*Complete resection
===Regimen variant #2, 1250/75/360===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019 	Phase 3 (E-RT-esc)	1a. CP1b. CVb1c. DC1d. GC	Longer EFS (co-primary endpoint)Median EFS: 31.6 vs 20.8 mo(HR 0.63, 97.38% CI 0.43-0.91)Higher 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====
*Gemcitabine (Gemzar) 1250 mg/m2 IV once per day on days 1 & 8
*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====
*Complete resection
===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 EuroPMC NCT02998528
=Adjuvant therapy=
==Cisplatin & Gemcitabine (GC)==
GC: Gemcitabine & Cisplatin
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Groen et al. 2019 (NVALT-8)	2007-2013 	Phase 3 (C)	GC & Nadroparin	Did not meet primary endpoint of RFSMedian RFS: 37.7 vs 65.2 mo(HR 1.30, 95% CI 0.88-1.89)
====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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NTR1250/1217
=Advanced or metastatic disease, first-line=
==Atezolizumab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Herbst et al. 2020 (IMpower110) 	2015-2018 	Phase 3 (E-RT-switch-ooc)	1a. Carboplatin & Gemcitabine1b. Cisplatin & Gemcitabine	Longer OS1 (primary endpoint)Median OS: 20.2 vs 13.1 mo(HR 0.59, 95% CI 0.40-0.89)
Peters et al. 2022 (B-FAST cohort C)	2017-09-22 to 2019-11-21	Phase 3 (E-switch-ooc) 	1a. Carboplatin & Gemcitabine1b. Cisplatin & Gemcitabine	Might have longer PFS (primary endpoint)Median PFS: 20.2 vs 13.1 mo(HR 0.77, 95% CI 0.59-1.00)
1Reported efficacy for IMpower110 is for TC3/IC3 only i.e., PD-L1 TC>50%.
====Biomarker eligibility criteria====
*IMpower110: 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
*B-FAST cohort C: blood-based TMB of at least 10
====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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02409342
##Update: Jassem J, de Marinis F, Giaccone G, Vergnenegre A, Barrios CH, Morise M, Felip E, Oprean C, Kim YC, Andric Z, Mocci S, Enquist I, Komatsubara K, McCleland M, Kuriki H, Villalobos M, Phan S, Spigel DR, Herbst RS. Updated Overall Survival Analysis From IMpower110: Atezolizumab Versus Platinum-Based Chemotherapy in Treatment-Naive Programmed Death-Ligand 1-Selected NSCLC. J Thorac Oncol. 2021 Nov;16(11):1872-1882. Epub 2021 Jul 12. link to original article EuroPMC
#B-FAST cohort C: Peters S, Dziadziuszko R, Morabito A, Felip E, Gadgeel SM, Cheema P, Cobo M, Andric Z, Barrios CH, Yamaguchi M, Dansin E, Danchaivijitr P, Johnson M, Novello S, Mathisen MS, Shagan SM, Schleifman E, Wang J, Yan M, Mocci S, Voong D, Fabrizio DA, Shames DS, Riehl T, Gandara DR, Mok T. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial. Nat Med. 2022 Sep;28(9):1831-1839. Epub 2022 Aug 22. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03178552
==Carboplatin & Gemcitabine (GCb)==
GCb: Gemcitabine & Carboplatin
===Regimen variant #1, 5/1000===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Patil et al. 2019 	2013-2018 	Phase 3 (C)	GCb; low-dose Gemcitabine 	Non-inferior OS
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	1. Durvalumab 	Might have shorter OS
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	2. Durvalumab & Tremelimumab 	Did not meet co-primary endpoints of PFS/OS
Herbst et al. 2020 (IMpower110) 	2015-2018 	Phase 3 (C)	Atezolizumab 	Shorter OS1Median OS: 13.1 vs 20.2 mo(HR 1.69, 95% CI 1.12-2.50)
Peters et al. 2022 (B-FAST cohort C)	2017-09-22 to 2019-11-21	Phase 3 (C)	Atezolizumab 	Might have shorter PFS (primary endpoint)Median PFS: 13.1 vs 20.2 mo(HR 1.30, 95% CI 1.00-1.69)
Zhou et al. 2021 (ORIENT-12) 	2018-09-25 to 2019-07-26	Phase 3 (C)	1a. GCb & Sintilimab1b. GC & Sintilimab	Shorter PFSMedian PFS: 4.9 vs 5.5 mo(HR 1.85, 95% CI 1.47-2.38)
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.
====Biomarker eligibility criteria====
*B-FAST cohort C: blood-based TMB of at least 10
====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 varying durations: 4 to 6 cycles (B-FAST cohort C, IMpower110, MYSTIC, ORIENT-12); 6 cycles (Patil et al. 2019)
===Regimen variant #2, 5.5/1000===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Edelman et al. 2017 (CALGB 30801)	2010-2013 	Phase 3 (C)	GCb & Celecoxib	Did not meet primary endpoint of PFSMedian PFS: 5.26 vs 5.16 mo(HR 0.93, 95% CI 0.73-1.17)
====Biomarker eligibility criteria====
*COX-2 expression at least 2
====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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in supplement have been reviewed by our editors EuroPMC NCT02453282
##PRO analysis: Garon EB, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, Robinet G, Le Moulec S, Natale R, Schneider J, Shepherd FA, Garassino MC, Geater SL, Szekely ZP, Van Ngoc T, Liu F, Scheuring U, Patel N, Peters S, Rizvi NA. Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Clin Lung Cancer. 2021 Jul;22(4):301-312.e8. Epub 2021 Feb 19. link to original article EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02409342
##Update: Jassem J, de Marinis F, Giaccone G, Vergnenegre A, Barrios CH, Morise M, Felip E, Oprean C, Kim YC, Andric Z, Mocci S, Enquist I, Komatsubara K, McCleland M, Kuriki H, Villalobos M, Phan S, Spigel DR, Herbst RS. Updated Overall Survival Analysis From IMpower110: Atezolizumab Versus Platinum-Based Chemotherapy in Treatment-Naive Programmed Death-Ligand 1-Selected NSCLC. J Thorac Oncol. 2021 Nov;16(11):1872-1882. Epub 2021 Jul 12. link to original article EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03629925
#B-FAST cohort C: Peters S, Dziadziuszko R, Morabito A, Felip E, Gadgeel SM, Cheema P, Cobo M, Andric Z, Barrios CH, Yamaguchi M, Dansin E, Danchaivijitr P, Johnson M, Novello S, Mathisen MS, Shagan SM, Schleifman E, Wang J, Yan M, Mocci S, Voong D, Fabrizio DA, Shames DS, Riehl T, Gandara DR, Mok T. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial. Nat Med. 2022 Sep;28(9):1831-1839. Epub 2022 Aug 22. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03178552
==Carboplatin & Gemcitabine (GCb) & Sintilimab==
GCb & Sintilimab: Gemcitabine, Carboplatin, Sintilimab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2021 (ORIENT-12)	2018-09-25 to 2019-07-26	Phase 3 (C)	1a. GCb1b. GC	Longer PFS (primary endpoint)Median PFS: 5.5 vs 4.9 mo(HR 0.54, 95% CI 0.42-0.68)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
*Gemcitabine (Gemzar) as follows:
**Cycles 1 to 4 up to 6: 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
====Immunotherapy====
*Sintilimab (Tyvyt) 200 mg IV once on day 1
21-day cycle for up to 39 cycles
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03629925
==Carboplatin & nab-Paclitaxel (CnP)==
CnP: Carboplatin & nab-Paclitaxel
===Regimen variant #1, AUC 5===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2024 (ASTRUM-004)	2019-08-13 to 2021-02-25	Phase 3 (C)	CnP & Serplulimab	Shorter OS (secondary endpoint)Median OS: 18.2 vs 22.7 mo(HR 1.37, 95% CI 1.08-1.72)Shorter PFS (primary endpoint)Median PFS: 5.7 vs 8.3 mo(HR 1.89, 95% CI 1.49-2.38)
Note: this was the lower bound of dosing of carboplatin in ASTRUM-004.
====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
Jotte et al. 2020 (IMpower131) 	2015-2017 	Phase 3 (C) 	1. A+CnP 	Shorter PFS
Jotte et al. 2020 (IMpower131) 	2015-2017 	Phase 3 (C) 	2. A+CP 	Not reported
Kogure et al. 2022 (CAPITAL) 	2016-2020 	Phase 3 (E-esc)	Docetaxel 	Longer OS (primary endpoint)Median OS: 16.9 vs 10.9 mo(HR 0.52, 90% CI 0.38-0.70)
Paz-Ares et al. 2018 (KEYNOTE-407) 	2016-08-19 to 2017-12-28	Phase 3 (C) 	1a. CP & Pembrolizumab1b. CnP & Pembrolizumab	Shorter OS1Median OS: 11.6 vs 17.1 mo(HR 1.41, 95% CI 1.14-1.72)
Cheng et al. 2021 (KEYNOTE-407 China Extension)	2017-04-21 to 2018-08-28	Phase 3 (C) 	1a. CP & Pembrolizumab1b. CnP & Pembrolizumab	Shorter OSOS24: 31.7% vs 56.9%(HR 2.27, 95% CI 1.43-3.57)Shorter PFSPFS24: 3.3% vs 24.2%(HR 2.86, 95% CI 1.92-4.17)
Zhou et al. 2024 (ASTRUM-004) 	2019-08-13 to 2021-02-25	Phase 3 (C) 	CnP & Serplulimab 	Shorter OS (secondary endpoint)Median OS: 18.2 vs 22.7 mo(HR 1.37, 95% CI 1.08-1.72)Shorter PFS (primary endpoint)Median PFS: 5.7 vs 8.3 mo(HR 1.89, 95% CI 1.49-2.38)
1Reported efficacy for KEYNOTE-407 is based on the 2021 update.
Note: this was the upper bound of dosing of carboplatin in ASTRUM-004. CAPITAL included patients that were 70 and older.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1
*Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
21-day cycle for varying durations: 4 cycles (KEYNOTE-407, KEYNOTE-407 China Extension); 4 to 6 cycles (ASTRUM-004, IMpower131); indefinitely (CAPITAL)
===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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02775435
##HRQoL analysis: Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gümüş M, Laktionov K, Hermes B, Cicin I, Rodríguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. Epub 2019 Nov 21. link to original article EuroPMC
##Update: Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazières J, Hermes B, Cicin I, Medgyasszay B, Rodríguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. Epub 2020 Jun 26. link to original article EuroPMC
##Update: Novello S, Kowalski DM, Luft A, Gümüş M, Vicente D, Mazières J, Rodríguez-Cid J, Tafreshi A, Cheng Y, Lee KH, Golf A, Sugawara S, Robinson AG, Halmos B, Jensen E, Schwarzenberger P, Pietanza MC, Paz-Ares L. Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. J Clin Oncol. 2023 Apr 10;41(11):1999-2006. Epub 2023 Feb 3. link to original article link to PMC article EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02367794
#KEYNOTE-407 China Extension: Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03875092
#CAPITAL: Kogure Y, Iwasawa S, Saka H, Hamamoto Y, Kada A, Hashimoto H, Atagi S, Takiguchi Y, Ebi N, Inoue A, Kurata T, Okamoto I, Yamaguchi M, Harada T, Seike M, Ando M, Saito AM, Kubota K, Takenoyama M, Seto T, Yamamoto N, Gemma A. Efficacy and safety of carboplatin with nab-paclitaxel versus docetaxel in older patients with squamous non-small-cell lung cancer (CAPITAL): a randomised, multicentre, open-label, phase 3 trial. Lancet Healthy Longev. 2021 Dec;2(12):e791-e800. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000019843
#ASTRUM-004: Zhou C, Hu Y, Arkania E, Kilickap S, Ying K, Xu F, Wu L, Wang X, Viguro M, Makharadze T, Sun H, Luo F, Shi J, Zang A, Pan Y, Chen Z, Jia Z, Kuchava V, Lu P, Zhang L, Cheng Y, Kang W, Wang Q, Yu H, Li J, Zhu J; ASTRUM-004 Investigators. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell. 2024 Feb 12;42(2):198-208.e3. Epub 2024 Jan 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04033354
==Carboplatin & nab-Paclitaxel (CnP) & Atezolizumab==
A+CnP: Atezolizumab, Carboplatin, nab-Paclitaxel
CnP & Atezolizumab: Carboplatin, nab-Paclitaxel, Atezolizumab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Jotte et al. 2020 (IMpower131)	2015-2017 	Phase 3 (E-esc)	1. CnP 	Longer PFS (co-primary endpoint)Median PFS: 6.3 vs 5.6 mo(HR 0.71, 95% CI 0.60-0.85)
Jotte et al. 2020 (IMpower131)	2015-2017 	Phase 3 (E-esc)	2. A+CP 	Not reported
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 6 IV once on day 1
*Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
**Cycles 1 to 4 up 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02367794
==Carboplatin & nab-Paclitaxel (CnP) & Pembrolizumab==
===Regimen variant #1, AUC 5===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tan et al. 2023 (CANOPY-1)	2019-06-25 to 2020-01-17	Phase 3 (C)	1a. CP, Canakinumab, Pembrolizumab1b. CnP, Canakinumab, Pembrolizumab	Did not meet co-primary endpoint of PFSMedian PFS: 6.8 vs 6.8 mo(HR 1.18, 95% CI 0.92-1.49)Did not meet co-primary endpoint of OSMedian OS: 20.2 vs 20.8 mo(HR 1.15, 95% CI 0.91-1.43)
====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====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #2, AUC 6===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Paz-Ares et al. 2018 (KEYNOTE-407) 	2016-08-19 to 2017-12-28	Phase 3 (E-RT-esc)	1a. CP1b. Carboplatin & nab-Paclitaxel 	Longer OS1 (co-primary endpoint)Median OS: 17.1 vs 11.6 mo (HR 0.71, 95% CI 0.58-0.88)
Cheng et al. 2021 (KEYNOTE-407 China Extension)	2017-04-21 to 2018-08-28	Phase 3 (E-RT-esc)	1a. CP1b. Carboplatin & nab-Paclitaxel 	Longer OS (co-primary endpoint)OS24: 56.9% vs 31.7%(HR 0.44, 95% CI 0.28-0.70)Longer PFS (co-primary endpoint)PFS24: 24.2% vs 3.3%(HR 0.35, 95% CI 0.24-0.52)
Shiraishi et al. 2024 (JCOG2007) 	2021-04-06 to 2023-03-30	Phase 3 (C) 	1a. CP, Ipilimumab, Nivolumab1b. CnP, Ipilimumab, Nivolumab 	Did not meet primary endpoint of OSMedian OS: 20.5 vs 23.7 mo(HR 1.02, 95% CI 0.75-1.39)
Awaiting publication (KEYVIBE-007) 	2022-2025 	Phase 3 (C) 	1a. CP, Pembrolizumab, Vibostolimab1b. CnP, Pembrolizumab, Vibostolimab	TBD if different co-primary endpoints of PFS/OS
1Reported efficacy for KEYNOTE-407 is based on the 2021 update.
====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====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1, given first
21-day cycle for up to 35 cycles (2 years)
===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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02775435
##HRQoL analysis: Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gümüş M, Laktionov K, Hermes B, Cicin I, Rodríguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. Epub 2019 Nov 21. link to original article EuroPMC
##Update: Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazières J, Hermes B, Cicin I, Medgyasszay B, Rodríguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. Epub 2020 Jun 26. link to original article EuroPMC
##Update: Novello S, Kowalski DM, Luft A, Gümüş M, Vicente D, Mazières J, Rodríguez-Cid J, Tafreshi A, Cheng Y, Lee KH, Golf A, Sugawara S, Robinson AG, Halmos B, Jensen E, Schwarzenberger P, Pietanza MC, Paz-Ares L. Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. J Clin Oncol. 2023 Apr 10;41(11):1999-2006. Epub 2023 Feb 3. link to original article link to PMC article EuroPMC
#KEYNOTE-407 China Extension: Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03875092
#CANOPY-1: Tan DSW, Felip E, de Castro G, Solomon BJ, Greystoke A, Cho BC, Cobo M, Kim TM, Ganguly S, Carcereny E, Paz-Ares L, Bennouna J, Garassino MC, Schenker M, Kim SW, Brase JC, Bury-Maynard D, Passos VQ, Deudon S, Dharan B, Song Y, Caparica R, Johnson BE. Canakinumab Versus Placebo in Combination With First-Line Pembrolizumab Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Results From the CANOPY-1 Trial. J Clin Oncol. 2024 Jan 10;42(2):192-204. Epub 2023 Dec 1. link to original article dosing details in supplement have been reviewed by our editors EuroPMC NCT03631199
#JCOG2007: Shiraishi Y, Nomura S, Sugawara S, Horinouchi H, Yoneshima Y, Hayashi H, Azuma K, Hara S, Niho S, Morita R, Yamaguchi M, Yokoyama T, Yoh K, Kurata T, Okamoto H, Okamoto M, Kijima T, Kasahara K, Fujiwara Y, Murakami S, Kanda S, Akamatsu H, Takemoto S, Kaneda H, Kozuki T, Ando M, Sekino Y, Fukuda H, Ohe Y, Okamoto I. Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial. Lancet Respir Med. 2024 Nov;12(11):877-887. Epub 2024 Aug 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC jRCTs031210013
#KEYLYNK-008: NCT03976362
#KEYVIBE-007: NCT05226598
==Carboplatin & nab-Paclitaxel (CnP) & Serplulimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Zhou et al. 2024 (ASTRUM-004)	2019-08-13 to 2021-02-25	Phase 3 (E-RT-esc)	CnP 	Longer OS (secondary endpoint)Median OS: 22.7 vs 18.2 mo(HR 0.73, 95% CI 0.58-0.93)Longer PFS (primary endpoint)Median PFS: 8.3 vs 5.7 mo(HR 0.53, 95% CI 0.42-0.67)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 or 6 IV once on day 1
*Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
**Cycles 1 to 4 up to 6: 100 mg/m2 IV once per day on days 1, 8, 15
====Immunotherapy====
*Serplulimab (Hansizhuang) 4.5 mg/kg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
===References===
#ASTRUM-004: Zhou C, Hu Y, Arkania E, Kilickap S, Ying K, Xu F, Wu L, Wang X, Viguro M, Makharadze T, Sun H, Luo F, Shi J, Zang A, Pan Y, Chen Z, Jia Z, Kuchava V, Lu P, Zhang L, Cheng Y, Kang W, Wang Q, Yu H, Li J, Zhu J; ASTRUM-004 Investigators. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell. 2024 Feb 12;42(2):198-208.e3. Epub 2024 Jan 4. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04033354
==Carboplatin & nab-Paclitaxel (CnP) & Tislelizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wang et al. 2021 (RATIONALE 307)	2018-07 to 2019-06 	Phase 3 (E-esc)	1. CP 	Longer PFS1 (primary endpoint)Median PFS: 9.6 vs 5.5 mo(sHR 0.43, 95% CI 0.31-0.60)
Wang et al. 2021 (RATIONALE 307)	2018-07 to 2019-06 	Phase 3 (E-esc)	2. CP & Tislelizumab	Not reported
1Reported efficacy is based on the 2024 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
*Paclitaxel, nanoparticle albumin-bound (Abraxane) as follows:
**Cycles 1 to 4 up to 6: 100 mg/m2 IV once per day on days 1, 8, 15
====Immunotherapy====
*Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
===References===
# RATIONALE 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03594747
##HRQoL analysis: Wang J, Yu X, Barnes G, Leaw S, Bao Y, Tang B. The effects of tislelizumab plus chemotherapy as first-line treatment on health-related quality of life of patients with advanced squamous non-small cell lung cancer: Results from a phase 3 randomized clinical trial. Cancer Treat Res Commun. 2022;30:100501. Epub 2021 Dec 17. link to original article EuroPMC
##Update: Wang J, Lu S, Yu X, Hu Y, Zhao J, Sun M, Yu Y, Hu C, Yang K, Song Y, Lin X, Liang L, Leaw S, Zheng W. Tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: final analysis of the randomized, phase III RATIONALE-307 trial. ESMO Open. 2024 Oct;9(10):103727. Epub 2024 Sep 25. link to original article link to PMC article EuroPMC
==Carboplatin & Paclitaxel (CP)==
TC: Taxol (Paclitaxel) & Carboplatin
CP: Carboplatin & Paclitaxel
===Regimen variant #1, 5/175===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Wang et al. 2021 (RATIONALE 307)	2018-07 to 2019-06 	Phase 3 (C)	1. CP & Tislelizumab2. CnP & Tislelizumab	Shorter PFS
Ren et al. 2021 (CameL-Sq) 	2018-11-26 to 2019-12-31	Phase 3 (C)	CP & Camrelizumab 	Shorter OS (secondary endpoint)Median OS: 14.5 vs NYR mo(HR 1.82, 95% CI 1.33-2.50)Shorter PFS (primary endpoint)
Zhou et al. 2022 (GEMSTONE-302) 	2018-2020 	Phase 3 (C)	CP & Sugemalimab 	Shorter PFS (primary endpoint)Median PFS: 4.9 vs 9 mo(HR 2.08, 95% CI 1.67-2.56)Shorter OS1 (secondary endpoint)Median OS: 16.9 vs 25.4 mo(HR 1.54, 95% CI 1.19-2.00)
Zhong et al. 2024 (AK105-302) 	2018-12-20 to 2020-10-10	Phase 3 (C)	CP & Penpulimab 	Shorter PFSMedian PFS: 4.2 vs 7.6 mo(HR 2.33, 95% CI 1.79-3.03)
1Reported efficacy for GEMSTONE-302 is based on 2023 update.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 5 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for varying durations: 4 cycles (AK105-302, GEMSTONE-302); 4 to 6 cycles (CameL-Sq, RATIONALE 307)
===Regimen variant #2, 5/200===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mok et al. 2019 (KEYNOTE-042)	2014-2017 	Phase 3 (C)	Pembrolizumab	Shorter OS
Note: 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 #3, 6/175===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Govindan et al. 2017 (CA184-104)	2011-2015 	Phase 3 (C)	TC & Ipilimumab	Did not meet primary endpoint of OSMedian OS: 12.4 vs 13.4 mo(HR 1.10, 95% CI 0.93-1.30)
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once on day 1
*Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
====Supportive therapy====
*Corticosteroids could be used as premedication for paclitaxel infusion.
21-day cycle for up to 6 cycles
===Regimen variant #4, 6/200===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Mok et al. 2019 (KEYNOTE-042) 	2014-2017 	Phase 3 (C)	Pembrolizumab 	Shorter OS
Ramalingam et al. 2021 (M11-089) 	2014-2019 	Phase 3 (C)	CP & Veliparib 	Did not meet primary endpoint of OS1Median OS: 11.1 vs 11.9 mo(HR 1.10, 95% CI 0.91-1.34)
Paz-Ares et al. 2018 (KEYNOTE-407) 	2016-08-19 to 2017-12-28	Phase 3 (C)	1a. CP & Pembrolizumab1b. CnP & Pembrolizumab	Shorter OS2Median OS: 11.6 vs 17.1 mo(HR 1.41, 95% CI 1.14-1.72)
Cheng et al. 2021 (KEYNOTE-407 China Extension)	2017-04-21 to 2018-08-28	Phase 3 (C)	1a. CP & Pembrolizumab1b. CnP & Pembrolizumab	Shorter OSOS24: 31.7% vs 56.9%(HR 2.27, 95% CI 1.43-3.57)Shorter PFSPFS24: 3.3% vs 24.2%(HR 2.86, 95% CI 1.92-4.17)
Paz-Ares et al. 2021 (CheckMate 9LA) 	2017-2019 	Phase 3 (C)	CP, Ipilimumab, Nivolumab 	Shorter OS3 (primary endpoint)Median OS: 11 vs 15.8 mo(HR 1.39, 95% CI 1.16-1.64)
1The primary endpoint was limited to current smokers, which made up 57% of the cohort.
2Reported efficacy for KEYNOTE-407 is based on the 2021 update.
3Reported efficacy for CheckMate 9LA is based on the 2021 update.
====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 varying durations: 4 cycles (CheckMate 9LA, KEYNOTE-407, KEYNOTE-407 China Extension); 6 cycles (KEYNOTE-042)
===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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02775435
##HRQoL analysis: Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gümüş M, Laktionov K, Hermes B, Cicin I, Rodríguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. Epub 2019 Nov 21. link to original article EuroPMC
##Update: Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazières J, Hermes B, Cicin I, Medgyasszay B, Rodríguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. Epub 2020 Jun 26. link to original article EuroPMC
##Update: Novello S, Kowalski DM, Luft A, Gümüş M, Vicente D, Mazières J, Rodríguez-Cid J, Tafreshi A, Cheng Y, Lee KH, Golf A, Sugawara S, Robinson AG, Halmos B, Jensen E, Schwarzenberger P, Pietanza MC, Paz-Ares L. Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. J Clin Oncol. 2023 Apr 10;41(11):1999-2006. Epub 2023 Feb 3. link to original article link to PMC article EuroPMC
#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 EuroPMC 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 EuroPMC
# 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03215706
## Update: Reck M, 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, Reyes F, Souquet PJ, De Marchi P, Martin C, Pérol M, Scherpereel A, Lu S, Paz-Ares L, Carbone DP, Memaj A, Marimuthu S, Zhang X, Tran P, John T. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update. ESMO Open. 2021 Oct;6(5):100273. Epub 2021 Oct 1. Erratum in: ESMO Open. 2021 Dec;6(6):100345. link to original article link to PMC article EuroPMC
# RATIONALE 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03594747
##HRQoL analysis: Wang J, Yu X, Barnes G, Leaw S, Bao Y, Tang B. The effects of tislelizumab plus chemotherapy as first-line treatment on health-related quality of life of patients with advanced squamous non-small cell lung cancer: Results from a phase 3 randomized clinical trial. Cancer Treat Res Commun. 2022;30:100501. Epub 2021 Dec 17. link to original article EuroPMC
##Update: Wang J, Lu S, Yu X, Hu Y, Zhao J, Sun M, Yu Y, Hu C, Yang K, Song Y, Lin X, Liang L, Leaw S, Zheng W. Tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: final analysis of the randomized, phase III RATIONALE-307 trial. ESMO Open. 2024 Oct;9(10):103727. Epub 2024 Sep 25. link to original article link to PMC article EuroPMC
# M11-089: Ramalingam SS, Novello S, Guclu SZ, Bentsion D, Zvirbule Z, Szilasi M, Bernabe R, Syrigos K, Byers LA, Clingan P, Bar J, Vokes EE, Govindan R, Dunbar M, Ansell P, He L, Huang X, Sehgal V, Glasgow J, Bach BA, Mazieres J. Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study. J Clin Oncol. 2021 Nov 10;39(32):3633-3644. Epub 2021 Aug 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02106546
#KEYNOTE-407 China Extension: Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03875092
# CameL-Sq: Ren S, Chen J, Xu X, Jiang T, Cheng Y, Chen G, Pan Y, Fang Y, Wang Q, Huang Y, Yao W, Wang R, Li X, Zhang W, Zhang Y, Hu S, Guo R, Shi J, Wang Z, Cao P, Wang D, Fang J, Luo H, Geng Y, Xing C, Lv D, Zhang Y, Yu J, Cang S, Yang Z, Shi W, Zou J, Zhou C; CameL-sq Study Group. Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial. J Thorac Oncol. 2022 Apr;17(4):544-557. Epub 2021 Dec 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03668496
# GEMSTONE-302: Zhou C, Wang Z, Sun Y, Cao L, Ma Z, Wu R, Yu Y, Yao W, Chang J, Chen J, Zhuang W, Cui J, Chen X, Lu Y, Shen H, Wang J, Li P, Qin M, Lu D, Yang J. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol. 2022 Feb;23(2):220-233. Epub 2022 Jan 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03789604
##Update: Zhou C, Wang Z, Sun M, Cao L, Ma Z, Wu R, Yu Y, Yao W, Sun S, Chen J, Zhuang W, Cui J, Chen X, Lu Y, Shen H, Hu C, Liu J, Liu Y, Wang M, Li X, Sun P, Shu Y, Zhou J, Li J, Gu K, Wang C, Zhao H, Zhang Y, Liu C, Wang J, Chen R, Qin M, Wang H, Yang J. Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Nat Cancer. 2023 Jun;4(6):860-871. Epub 2023 Jun 15. link to original article EuroPMC
#AK105-302: Zhong H, Sun S, Chen J, Wang Z, Zhao Y, Zhang G, Chen G, Zhou M, Zhou J, Du Y, Wu L, Xu Z, Mei X, Zhang W, He J, Cui J, Zhang Z, Luo H, Liu W, Sun M, Wu J, Shen Y, Zhang S, Yang N, Wang M, Lu J, Li K, Yao W, Sun Q, Yue H, Wang L, Ye S, Li B, Zhuang X, Pan Y, Zhang M, Shu Y, He Z, Pan L, Ling Y, Liu S, Zhang Q, Jiao S, Han B. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial. Lancet Respir Med. 2024 May;12(5):355-365. Epub 2024 Jan 31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03866993
# ENREACH-L-01: NCT04474119
==Carboplatin & Paclitaxel (CP) & Camrelizumab==
CP & Camrelizumab: Carboplatin, Paclitaxel, Camrelizumab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Ren et al. 2021 (CameL-Sq)	2018-11-26 to 2019-12-31	Phase 3 (E-esc)	CP 	Longer OS (secondary endpoint)Median OS: NYR vs 14.5 mo(HR 0.55, 95% CI 0.40-0.75)Longer PFS (primary endpoint)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 4 up to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Camrelizumab (AiRuiKa) 200 mg IV once on day 1
21-day cycles
===References===
# CameL-Sq: Ren S, Chen J, Xu X, Jiang T, Cheng Y, Chen G, Pan Y, Fang Y, Wang Q, Huang Y, Yao W, Wang R, Li X, Zhang W, Zhang Y, Hu S, Guo R, Shi J, Wang Z, Cao P, Wang D, Fang J, Luo H, Geng Y, Xing C, Lv D, Zhang Y, Yu J, Cang S, Yang Z, Shi W, Zou J, Zhou C; CameL-sq Study Group. Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial. J Thorac Oncol. 2022 Apr;17(4):544-557. Epub 2021 Dec 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03668496
==Carboplatin & Paclitaxel (CP) & Ipilimumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Govindan et al. 2017 (CA184-104)	2011-2015 	Phase 3 (E-esc)	Carboplatin & Paclitaxel	Did not meet primary endpoint of OSMedian OS: 13.4 vs 12.4 mo(HR 0.91, 95% CI 0.77-1.07)
Note: this is the "phased" approach to this regimen.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 6: AUC 6 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Ipilimumab (Yervoy) as follows:
**Cycle 3 onwards: 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 5 cycles, then 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01285609
==Carboplatin & Paclitaxel (CP) & Ipilimumab, Nivolumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Paz-Ares et al. 2021 (CheckMate 9LA)	2017-2019 	Phase 3 (E-RT-switch-ooc)	CP 	Longer OS1 (primary endpoint)Median OS: 15.8 vs 11 mo(HR 0.72, 95% CI 0.61-0.86)
1Reported efficacy is based on the 2021 update.
====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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03215706
## Update: Reck M, 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, Reyes F, Souquet PJ, De Marchi P, Martin C, Pérol M, Scherpereel A, Lu S, Paz-Ares L, Carbone DP, Memaj A, Marimuthu S, Zhang X, Tran P, John T. First-line nivolumab plus ipilimumab with two cycles of chemotherapy versus chemotherapy alone (four cycles) in advanced non-small-cell lung cancer: CheckMate 9LA 2-year update. ESMO Open. 2021 Oct;6(5):100273. Epub 2021 Oct 1. Erratum in: ESMO Open. 2021 Dec;6(6):100345. link to original article link to PMC article EuroPMC
==Carboplatin & Paclitaxel (CP) & Pembrolizumab==
===Regimen variant #1, AUC 5===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Tan et al. 2023 (CANOPY-1)	2019-06-25 to 2020-01-17	Phase 3 (C)	1a. CP, Canakinumab, Pembrolizumab1b. CnP, Canakinumab, Pembrolizumab	Did not meet co-primary endpoint of PFSMedian PFS: 6.8 vs 6.8 mo(HR 1.18, 95% CI 0.92-1.49)Did not meet co-primary endpoint of OSMedian OS: 20.2 vs 20.8 mo(HR 1.15, 95% CI 0.91-1.43)
====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====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1, given first
21-day cycle for up to 35 cycles (2 years)
===Regimen variant #2, AUC 6===
FDA-recommended dose
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Paz-Ares et al. 2018 (KEYNOTE-407) 	2016-08-19 to 2017-12-28	Phase 3 (E-RT-esc)	1a. CP1b. Carboplatin & nab-Paclitaxel 	Longer OS1 (co-primary endpoint)Median OS: 17.1 vs 11.6 mo (HR 0.71, 95% CI 0.58-0.88)
Cheng et al. 2021 (KEYNOTE-407 China Extension)	2017-04-21 to 2018-08-28	Phase 3 (E-RT-esc)	1a. CP1b. Carboplatin & nab-Paclitaxel 	Longer OS (co-primary endpoint)OS24: 56.9% vs 31.7%(HR 0.44, 95% CI 0.28-0.70)Longer PFS (co-primary endpoint)PFS24: 24.2% vs 3.3%(HR 0.35, 95% CI 0.24-0.52)
Shiraishi et al. 2024 (JCOG2007) 	2021-04-06 to 2023-03-30	Phase 3 (C) 	1a. CP, Ipilimumab, Nivolumab1b. CnP, Ipilimumab, Nivolumab 	Did not meet primary endpoint of OSMedian OS: 20.5 vs 23.7 mo(HR 1.02, 95% CI 0.75-1.39)
Awaiting publication (KEYVIBE-007) 	2022-2025 	Phase 3 (C) 	1a. CP, Pembrolizumab, Vibostolimab1b. CnP, Pembrolizumab, Vibostolimab	TBD if different co-primary endpoints of PFS/OS
1Reported efficacy for KEYNOTE-407 is based on the 2021 update.
====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====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1, given first
21-day cycle for up to 35 cycles (2 years)
===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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02775435
##HRQoL analysis: Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gümüş M, Laktionov K, Hermes B, Cicin I, Rodríguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. Epub 2019 Nov 21. link to original article EuroPMC
##Update: Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazières J, Hermes B, Cicin I, Medgyasszay B, Rodríguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. Epub 2020 Jun 26. link to original article EuroPMC
##Update: Novello S, Kowalski DM, Luft A, Gümüş M, Vicente D, Mazières J, Rodríguez-Cid J, Tafreshi A, Cheng Y, Lee KH, Golf A, Sugawara S, Robinson AG, Halmos B, Jensen E, Schwarzenberger P, Pietanza MC, Paz-Ares L. Pembrolizumab Plus Chemotherapy in Squamous Non-Small-Cell Lung Cancer: 5-Year Update of the Phase III KEYNOTE-407 Study. J Clin Oncol. 2023 Apr 10;41(11):1999-2006. Epub 2023 Feb 3. link to original article link to PMC article EuroPMC
#KEYNOTE-407 China Extension: Cheng Y, Zhang L, Hu J, Wang D, Hu C, Zhou J, Wu L, Cao L, Liu J, Zhang H, Sun H, Wang Z, Gao H, Sun Y, Li B, Hu X, Schwarzenberger P, Paz-Ares L. Pembrolizumab Plus Chemotherapy for Chinese Patients With Metastatic Squamous NSCLC in KEYNOTE-407. JTO Clin Res Rep. 2021 Sep 25;2(10):100225. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03875092
#CANOPY-1: Tan DSW, Felip E, de Castro G, Solomon BJ, Greystoke A, Cho BC, Cobo M, Kim TM, Ganguly S, Carcereny E, Paz-Ares L, Bennouna J, Garassino MC, Schenker M, Kim SW, Brase JC, Bury-Maynard D, Passos VQ, Deudon S, Dharan B, Song Y, Caparica R, Johnson BE. Canakinumab Versus Placebo in Combination With First-Line Pembrolizumab Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer: Results From the CANOPY-1 Trial. J Clin Oncol. 2024 Jan 10;42(2):192-204. Epub 2023 Dec 1. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03631199
#JCOG2007: Shiraishi Y, Nomura S, Sugawara S, Horinouchi H, Yoneshima Y, Hayashi H, Azuma K, Hara S, Niho S, Morita R, Yamaguchi M, Yokoyama T, Yoh K, Kurata T, Okamoto H, Okamoto M, Kijima T, Kasahara K, Fujiwara Y, Murakami S, Kanda S, Akamatsu H, Takemoto S, Kaneda H, Kozuki T, Ando M, Sekino Y, Fukuda H, Ohe Y, Okamoto I. Comparison of platinum combination chemotherapy plus pembrolizumab versus platinum combination chemotherapy plus nivolumab-ipilimumab for treatment-naive advanced non-small-cell lung cancer in Japan (JCOG2007): an open-label, multicentre, randomised, phase 3 trial. Lancet Respir Med. 2024 Nov;12(11):877-887. Epub 2024 Aug 16. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC jRCTs031210013
#KEYLYNK-008: NCT03976362
#KEYVIBE-007: NCT05226598
==Carboplatin & Paclitaxel (CP) & Penpulimab==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Zhong et al. 2024 (AK105-302)	2018-12-20 to 2020-10-10	Phase 3 (E-RT-esc)	CP 	Longer PFS (primary endpoint)Median PFS: 7.6 vs 4.2 mo(HR 0.43, 95% CI 0.33-0.56)
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 4: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Penpulimab (Anniko) 200 mg IV once on day 1
21-day cycles
===References===
#AK105-302: Zhong H, Sun S, Chen J, Wang Z, Zhao Y, Zhang G, Chen G, Zhou M, Zhou J, Du Y, Wu L, Xu Z, Mei X, Zhang W, He J, Cui J, Zhang Z, Luo H, Liu W, Sun M, Wu J, Shen Y, Zhang S, Yang N, Wang M, Lu J, Li K, Yao W, Sun Q, Yue H, Wang L, Ye S, Li B, Zhuang X, Pan Y, Zhang M, Shu Y, He Z, Pan L, Ling Y, Liu S, Zhang Q, Jiao S, Han B. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial. Lancet Respir Med. 2024 May;12(5):355-365. Epub 2024 Jan 31. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03866993
==Carboplatin & Paclitaxel (CP) & Sugemalimab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Zhou et al. 2022 (GEMSTONE-302)	2018-2020 	Phase 3 (E-esc)	CP 	Longer OS1 (secondary endpoint)Median OS: 25.4 vs 16.9 mo(HR 0.65, 95% CI 0.50-0.84)Longer PFS (primary endpoint)Median PFS: 9 vs 4.9 mo(HR 0.48, 95% CI 0.39-0.60)
1Reported efficacy is based on 2023 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4: AUC 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 4: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Sugemalimab (Cejemly) 1200 mg IV once on day 1
21-day cycles
===References===
# GEMSTONE-302: Zhou C, Wang Z, Sun Y, Cao L, Ma Z, Wu R, Yu Y, Yao W, Chang J, Chen J, Zhuang W, Cui J, Chen X, Lu Y, Shen H, Wang J, Li P, Qin M, Lu D, Yang J. Sugemalimab versus placebo, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer (GEMSTONE-302): interim and final analyses of a double-blind, randomised, phase 3 clinical trial. Lancet Oncol. 2022 Feb;23(2):220-233. Epub 2022 Jan 14. link to original article dosing details in abstract have been reviewed by our editors EuroPMC NCT03789604
##Update: Zhou C, Wang Z, Sun M, Cao L, Ma Z, Wu R, Yu Y, Yao W, Sun S, Chen J, Zhuang W, Cui J, Chen X, Lu Y, Shen H, Hu C, Liu J, Liu Y, Wang M, Li X, Sun P, Shu Y, Zhou J, Li J, Gu K, Wang C, Zhao H, Zhang Y, Liu C, Wang J, Chen R, Qin M, Wang H, Yang J. Interim survival analysis of the randomized phase III GEMSTONE-302 trial: sugemalimab or placebo plus chemotherapy as first-line treatment for metastatic NSCLC. Nat Cancer. 2023 Jun;4(6):860-871. Epub 2023 Jun 15. link to original article EuroPMC
==Carboplatin & Paclitaxel (CP) & Tislelizumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Wang et al. 2021 (RATIONALE 307)	2018-07 to 2019-06 	Phase 3 (E-esc)	1. CP 	Longer PFS1 (primary endpoint)Median PFS: 7.7 vs 5.5 mo(sHR 0.45, 95% CI 0.33-0.62)Might have longer OS1 (secondary endpoint)Median OS: 22.8 vs 20.2 mo(sHR 0.68, 95% CI 0.46-1.01)
Wang et al. 2021 (RATIONALE 307)	2018-07 to 2019-06 	Phase 3 (E-esc)	2. CnP & Tislelizumab	Not reported
1Reported efficacy is based on the 2024 update.
====Chemotherapy====
*Carboplatin (Paraplatin) as follows:
**Cycles 1 to 4 up to 6: AUC 5 IV once on day 1
*Paclitaxel (Taxol) as follows:
**Cycles 1 to 4 up to 6: 175 mg/m2 IV once on day 1
====Immunotherapy====
*Tislelizumab (Baizean) 200 mg IV once on day 1
21-day cycles
===References===
# RATIONALE 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03594747
##HRQoL analysis: Wang J, Yu X, Barnes G, Leaw S, Bao Y, Tang B. The effects of tislelizumab plus chemotherapy as first-line treatment on health-related quality of life of patients with advanced squamous non-small cell lung cancer: Results from a phase 3 randomized clinical trial. Cancer Treat Res Commun. 2022;30:100501. Epub 2021 Dec 17. link to original article EuroPMC
##Update: Wang J, Lu S, Yu X, Hu Y, Zhao J, Sun M, Yu Y, Hu C, Yang K, Song Y, Lin X, Liang L, Leaw S, Zheng W. Tislelizumab plus chemotherapy versus chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: final analysis of the randomized, phase III RATIONALE-307 trial. ESMO Open. 2024 Oct;9(10):103727. Epub 2024 Sep 25. link to original article link to PMC article EuroPMC
==Carboplatin & S-1==
===Regimen===
Study 	Dates of enrollment	Evidence
Tanaka et al. 2020 (WJOG7512L)	2013-2017 	Non-randomized part of phase 3 RCT
====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 4 cycles
====Subsequent treatment====
*S-1 maintenance versus no further treatment
===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 dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000010396
==Cisplatin & Docetaxel (DC)==
DC: Docetaxel & Cisplatin
CD: Cisplatin & Docetaxel
===Regimen variant #1, 75/75===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lu et al. 2018 (5501068)	2013-2015 	Phase 3 (C)	Docetaxel & Nedaplatin	Might have shorter 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 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Shukuya et al. 2015 (WJOG5208L)	2009-2012 	Phase 3 (C)	Docetaxel & Nedaplatin	Might have shorter OSMedian OS: 11.4 vs 13.6 mo(HR 1.23, 95% CI 0.98-1.54)
====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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02088515
==Cisplatin & Gemcitabine (GC)==
GC: Gemcitabine & Cisplatin
GP: Gemcitabine & Platinol (Cisplatin)
===Regimen variant #1, 75/1000===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	1. Durvalumab 	Might have shorter OS
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	2. Durvalumab & Tremelimumab 	Did not meet co-primary endpoints of PFS/OS
Zhang et al. 2021 (LY-TM-LPS-2016-01)	2016-12 to 2019-12 	Phase 3 (C)	Cisplatin & Paclitaxel liposomal	Did not meet primary endpoints of PFSMedian PFS: 5.5 vs 5.2 mo(HR 0.97, 95% CI 0.79-1.19)
Note: This was the lower bound of gemcitabine and cisplatin dosing in MYSTIC.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once on day 1
*Gemcitabine (Gemzar) 1000 mg/m2 IV over 2 hours once per day on days 1 & 8
21-day cycle for 4 to 6 cycles
===Regimen variant #2, 75/1250===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Thatcher et al. 2015 (SQUIRE) 	2010-2012 	Phase 3 (C)	Cisplatin, Gemcitabine, Necitumumab 	Seems to have shorter OSMedian OS: 9.9 vs 11.5 mo(HR 1.19, 95% CI 1.04-1.35)
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	1. Durvalumab 	Might have shorter OS
Rizvi et al. 2020 (MYSTIC) 	2015-07-21 to 2016-06-08	Phase 3 (C)	2. Durvalumab & Tremelimumab 	Did not meet co-primary endpoints of PFS/OS
Herbst et al. 2020 (IMpower110) 	2015-2018 	Phase 3 (C)	Atezolizumab 	Shorter OS1Median OS: 13.1 vs 20.2 mo(HR 1.69, 95% CI 1.12-2.50)
Peters et al. 2022 (B-FAST cohort C)	2017-09-22 to 2019-11-21	Phase 3 (C)	Atezolizumab 	Might have shorter PFS (primary endpoint)Median PFS: 13.1 vs 20.2 mo(HR 1.30, 95% CI 1.00-1.69)
Zhou et al. 2021 (ORIENT-12) 	2018-09-25 to 2019-07-26	Phase 3 (C)	1a. GCb & Sintilimab1b. GC & Sintilimab	Shorter PFSMedian PFS: 4.9 vs 5.5 mo(HR 1.85, 95% CI 1.47-2.38)
1Reported efficacy for IMpower110 is for TC3/IC3 only i.e., PD-L1 TC>50%.
====Biomarker eligibility criteria====
*B-FAST cohort C: blood-based TMB of at least 10
====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 (B-FAST cohort C, IMpower110, MYSTIC, ORIENT-12); 6 cycles (SQUIRE)
===Regimen variant #3, 80/1000 or 80/1250===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Rizvi et al. 2020 (MYSTIC)	2015-07-21 to 2016-06-08	Phase 3 (C)	1. Durvalumab 	Might have shorter OS
Rizvi et al. 2020 (MYSTIC)	2015-07-21 to 2016-06-08	Phase 3 (C)	2. Durvalumab & Tremelimumab	Did not meet co-primary endpoints of PFS/OS
Note: This was the upper bound of cisplatin dosing in MYSTIC.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV over 30 minutes once on day 1
*Gemcitabine (Gemzar) 1000 to 1250 mg/m2 IV over 2 hours once per day on days 1 & 8
21-day cycle for 4 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00981058
##HRQoL analysis: Reck M, Socinski MA, Luft A, Szczęsna A, Dediu M, Ramlau R, Losonczy G, Molinier O, Schumann C, Gralla RJ, Bonomi P, Brown J, Soldatenkova V, Chouaki N, Obasaju C, Peterson P, Thatcher N. The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial. J Thorac Oncol. 2016 Jun;11(6):808-18. Epub 2016 Mar 12. link to original article EuroPMC
##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 dosing details in supplement have been reviewed by our editors link to PMC article EuroPMC NCT02453282
##PRO analysis: Garon EB, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, Robinet G, Le Moulec S, Natale R, Schneider J, Shepherd FA, Garassino MC, Geater SL, Szekely ZP, Van Ngoc T, Liu F, Scheuring U, Patel N, Peters S, Rizvi NA. Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Clin Lung Cancer. 2021 Jul;22(4):301-312.e8. Epub 2021 Feb 19. link to original article EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02409342
##Update: Jassem J, de Marinis F, Giaccone G, Vergnenegre A, Barrios CH, Morise M, Felip E, Oprean C, Kim YC, Andric Z, Mocci S, Enquist I, Komatsubara K, McCleland M, Kuriki H, Villalobos M, Phan S, Spigel DR, Herbst RS. Updated Overall Survival Analysis From IMpower110: Atezolizumab Versus Platinum-Based Chemotherapy in Treatment-Naive Programmed Death-Ligand 1-Selected NSCLC. J Thorac Oncol. 2021 Nov;16(11):1872-1882. Epub 2021 Jul 12. link to original article EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03629925
#LY-TM-LPS-2016-01: Zhang J, Pan Y, Shi Q, Zhang G, Jiang L, Dong X, Gu K, Wang H, Zhang X, Yang N, Li Y, Xiong J, Yi T, Peng M, Song Y, Fan Y, Cui J, Chen G, Tan W, Zang A, Guo Q, Zhao G, Wang Z, He J, Yao W, Wu X, Chen K, Hu X, Hu C, Yue L, Jiang D, Wang G, Liu J, Yu G, Li J, Bai J, Xie W, Zhao W, Wu L, Zhou C. Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study. Cancer Commun (Lond). 2022 Jan;42(1):3-16. Epub 2021 Oct 26. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02996214
#B-FAST cohort C: Peters S, Dziadziuszko R, Morabito A, Felip E, Gadgeel SM, Cheema P, Cobo M, Andric Z, Barrios CH, Yamaguchi M, Dansin E, Danchaivijitr P, Johnson M, Novello S, Mathisen MS, Shagan SM, Schleifman E, Wang J, Yan M, Mocci S, Voong D, Fabrizio DA, Shames DS, Riehl T, Gandara DR, Mok T. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial. Nat Med. 2022 Sep;28(9):1831-1839. Epub 2022 Aug 22. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03178552
==Cisplatin & Gemcitabine (GC) & Necitumumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Thatcher et al. 2015 (SQUIRE)	2010-2012 	Phase 3 (E-RT-esc)	Cisplatin & Gemcitabine	Seems to have longer OS (primary endpoint)Median OS: 11.5 vs 9.9 mo(HR 0.84, 95% CI 0.74-0.96)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 75 mg/m2 IV over 2 hours once on day 1
*Gemcitabine (Gemzar) as follows:
**Cycles 1 to 6: 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 therapy====
*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===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00981058
##HRQoL analysis: Reck M, Socinski MA, Luft A, Szczęsna A, Dediu M, Ramlau R, Losonczy G, Molinier O, Schumann C, Gralla RJ, Bonomi P, Brown J, Soldatenkova V, Chouaki N, Obasaju C, Peterson P, Thatcher N. The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial. J Thorac Oncol. 2016 Jun;11(6):808-18. Epub 2016 Mar 12. link to original article EuroPMC
##Dataset: Project Data Sphere
==Cisplatin & Gemcitabine (GC) & Sintilimab==
GC & Sintilimab: Gemcitabine, Cisplatin, Sintilimab
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Zhou et al. 2021 (ORIENT-12)	2018-09-25 to 2019-07-26	Phase 3 (C)	1a. GCb1b. GC	Longer PFS (primary endpoint)Median PFS: 5.5 vs 4.9 mo(HR 0.54, 95% CI 0.42-0.68)
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 4 up to 6: 75 mg/m2 IV once on day 1
*Gemcitabine (Gemzar) as follows:
**Cycles 1 to 4 up to 6: 1000 mg/m2 IV over 30 minutes once per day on days 1 & 8
====Immunotherapy====
*Sintilimab (Tyvyt) 200 mg IV once on day 1
21-day cycle for up to 39 cycles
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT03629925
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kogure et al. 2022 (CAPITAL)	2016-2020 	Phase 3 (C)	CnP 	Shorter OSMedian OS: 10.9 vs 16.9 mo(HR 1.92, 90% CI 1.43-2.63)
Note: This trial enrolled patients who were 70 or older.
====Chemotherapy====
*Docetaxel (Taxotere) 60 mg/m2 IV over 60 minutes once on day 1
21-day cycles
===References===
#CAPITAL: Kogure Y, Iwasawa S, Saka H, Hamamoto Y, Kada A, Hashimoto H, Atagi S, Takiguchi Y, Ebi N, Inoue A, Kurata T, Okamoto I, Yamaguchi M, Harada T, Seike M, Ando M, Saito AM, Kubota K, Takenoyama M, Seto T, Yamamoto N, Gemma A. Efficacy and safety of carboplatin with nab-paclitaxel versus docetaxel in older patients with squamous non-small-cell lung cancer (CAPITAL): a randomised, multicentre, open-label, phase 3 trial. Lancet Healthy Longev. 2021 Dec;2(12):e791-e800. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000019843
==Docetaxel & Nedaplatin==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Shukuya et al. 2015 (WJOG5208L)	2009-2012 	Phase 3 (E-switch-ic)	Cisplatin & Docetaxel	Might have longer OS (primary endpoint)Median OS: 13.6 vs 11.4 mo(HR 0.81, 95% CI 0.65-1.02)
====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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT02088515
==Ipilimumab & Nivolumab==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hellmann et al. 2018 (CheckMate 227)	2015-08 to 2016-11 	Phase 3 (E-RT-switch-ooc)	1. Nivolumab 	Not reported
Hellmann et al. 2018 (CheckMate 227)	2015-08 to 2016-11 	Phase 3 (E-RT-switch-ooc)	2a. GC2b. GCb	Longer OS (co-primary endpoint)1OS60: 24% vs 14%
1Reported efficacy is based on the 2022 update. Note that the proportional hazards assumption was not met; HR is therefore not reported here.
====Biomarker eligibility criteria====
*PD-L1 expression of 1% or more
====Immunotherapy====
*Ipilimumab (Yervoy) 1 mg/kg IV once on day 1
*Nivolumab (Opdivo) 3 mg/kg IV once per day on days 1, 15, 29
42-day cycles
===References===
#CheckMate 227: Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018 May 31;378(22):2093-2104. Epub 2018 Apr 16. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT02477826
##PRO analysis: Reck M, Schenker M, Lee KH, Provencio M, Nishio M, Lesniewski-Kmak K, Sangha R, Ahmed S, Raimbourg J, Feeney K, Corre R, Franke FA, Richardet E, Penrod JR, Yuan Y, Nathan FE, Bhagavatheeswaran P, DeRosa M, Taylor F, Lawrance R, Brahmer J. Nivolumab plus ipilimumab versus chemotherapy as first-line treatment in advanced non-small-cell lung cancer with high tumour mutational burden: patient-reported outcomes results from the randomised, open-label, phase III CheckMate 227 trial. Eur J Cancer. 2019 Jul;116:137-147. Epub 2019 Jun 11. link to original article EuroPMC
##Update: Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. Epub 2019 Sep 28. link to original article EuroPMC
##Update: Paz-Ares LG, Ramalingam SS, Ciuleanu TE, Lee JS, Urban L, Caro RB, Park K, Sakai H, Ohe Y, Nishio M, Audigier-Valette C, Burgers JA, Pluzanski A, Sangha R, Gallardo C, Takeda M, Linardou H, Lupinacci L, Lee KH, Caserta C, Provencio M, Carcereny E, Otterson GA, Schenker M, Zurawski B, Alexandru A, Vergnenegre A, Raimbourg J, Feeney K, Kim SW, Borghaei H, O'Byrne KJ, Hellmann MD, Memaj A, Nathan FE, Bushong J, Tran P, Brahmer JR, Reck M. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial. J Thorac Oncol. 2022 Feb;17(2):289-308. Epub 2021 Oct 12. link to original article EuroPMC
##Update: Brahmer JR, Lee JS, Ciuleanu TE, Bernabe Caro R, Nishio M, Urban L, Audigier-Valette C, Lupinacci L, Sangha R, Pluzanski A, Burgers J, Mahave M, Ahmed S, Schoenfeld AJ, Paz-Ares LG, Reck M, Borghaei H, O'Byrne KJ, Gupta RG, Bushong J, Li L, Blum SI, Eccles LJ, Ramalingam SS. Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227. J Clin Oncol. 2023 Feb 20;41(6):1200-1212. Epub 2022 Oct 12. link to original article link to PMC article EuroPMC
=Maintenance after first-line therapy=
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tanaka et al. 2020 (WJOG7512L)	2013-2017 	Phase 3 (E-esc)	Observation	Longer PFS (primary endpoint)Median PFS: 1.6 vs 1 mo(HR 0.55, 95% CI 0.37-0.80)
====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 dosing details in manuscript have been reviewed by our editors EuroPMC UMIN000010396
=Advanced or metastatic disease, second-line=
==Afatinib monotherapy==
===Regimen variant #1, 30 mg/day===
FDA-recommended dose
Note: This is the FDA-recommended dose for patients with "severe renal impairment".
====Targeted therapy====
*Afatinib (Gilotrif) 30 mg PO once per day
Continued indefinitely
===Regimen variant #2, 40 mg/day===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Soria et al. 2015 (LUX-Lung 8)	2012-2014 	Phase 3 (E-RT-switch-ic)	Erlotinib 	Seems to have longer PFS (primary endpoint)Median PFS: 2.4 vs 1.9 mo(HR 0.82, 95% CI 0.68-1.00)Seems to have longer OS1 (secondary endpoint)Median OS: 7.8 vs 6.8 mo(HR 0.84, 95% CI 0.73-0.97)
1Reported efficacy for OS is based on the 2021 update.
====Targeted therapy====
*Afatinib (Gilotrif) 40 mg PO once per day on days 1 to 28, taken at least 1 hour before eating food
28-day cycles
====Dose and schedule modifications====
*LUX-Lung 8: Patients without grade 2 or higher adverse events could escalate to 50 mg PO once per day beginning with cycle 2.
===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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT01523587
##PRO analysis: Felip E, Hirsh V, Popat S, Cobo M, Fülöp A, Dayen C, Trigo JM, Gregg R, Waller CF, Soria JC, Goss GD, Gordon J, Wang B, Palmer M, Ehrnrooth E, Gadgeel SM. Symptom and Quality of Life Improvement in LUX-Lung 8, an Open-Label Phase III Study of Second-Line Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung After First-Line Platinum-Based Chemotherapy. Clin Lung Cancer. 2018 Jan;19(1):74-83.e11. Epub 2017 Jun 23. link to original article EuroPMC
##Update: Goss GD, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Isla D, Morabito A, Min YJ, Ardizzoni A, Bender S, Cseh A, Felip E. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung: Final analysis of the randomised phase 3 LUX-Lung 8 trial. EClinicalMedicine. 2021 Jun 18;37:100940. link to original article link to PMC article EuroPMC
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Shi et al. 2022 (ORIENT-3)	2017-08-25 to 2018-11-07	Phase 3 (C)	Sintilimab	Seems to have shorter OSMedian OS: 8.25 vs 11.79 mo(HR 1.35, 95% CI 1.04-1.79)
====Prior treatment criteria====
*Failure of first-line platinum-containing chemotherapy
====Chemotherapy====
*Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycles
===References===
#ORIENT-3: Shi Y, Wu L, Yu X, Xing P, Wang Y, Zhou J, Wang A, Shi J, Hu Y, Wang Z, An G, Fang Y, Sun S, Zhou C, Wang C, Ye F, Li X, Wang J, Wang M, Liu Y, Zhao Y, Yuan Y, Feng J, Chen Z, Shi J, Sun T, Wu G, Shu Y, Guo Q, Zhang Y, Song Y, Zhang S, Chen Y, Li W, Niu H, Hu W, Wang L, Huang J, Zhang Y, Cheng Y, Wu Z, Peng B, Sun J, Mancao C, Wang Y, Sun L. Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3). Cancer Commun (Lond). 2022 Dec;42(12):1314-1330. Epub 2022 Nov 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03150875
==Sintilimab monotherapy==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Shi et al. 2022 (ORIENT-3)	2017-08-25 to 2018-11-07	Phase 3 (E-switch-ooc)	Docetaxel 	Seems to have longer OS (primary endpoint)Median OS: 11.79 vs 8.25 mo(HR 0.74, 95% CI 0.56-0.96)
====Prior treatment criteria====
*Failure of first-line platinum-containing chemotherapy
====Immunotherapy====
*Sintilimab (Tyvyt) 200 mg IV once on day 1
21-day cycles
===References===
#ORIENT-3: Shi Y, Wu L, Yu X, Xing P, Wang Y, Zhou J, Wang A, Shi J, Hu Y, Wang Z, An G, Fang Y, Sun S, Zhou C, Wang C, Ye F, Li X, Wang J, Wang M, Liu Y, Zhao Y, Yuan Y, Feng J, Chen Z, Shi J, Sun T, Wu G, Shu Y, Guo Q, Zhang Y, Song Y, Zhang S, Chen Y, Li W, Niu H, Hu W, Wang L, Huang J, Zhang Y, Cheng Y, Wu Z, Peng B, Sun J, Mancao C, Wang Y, Sun L. Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer: an open-label, randomized controlled phase 3 trial (ORIENT-3). Cancer Commun (Lond). 2022 Dec;42(12):1314-1330. Epub 2022 Nov 6. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03150875
=Advanced or metastatic disease, subsequent lines of therapy=
Note: this section includes regimens that were tested in second-line and beyond.
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Brahmer et al. 2015 (CheckMate 017)	2012-10 to 2013-12 	Phase 3 (C)	Nivolumab 	Shorter OSMedian OS: 6 vs 9 mo(HR 1.69, 95% CI 1.27-2.27)
====Prior treatment criteria====
*CheckMate 017: One prior platinum-containing regimen
====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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 link to PMC article EuroPMC
##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 EuroPMC
##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 link to PMC article EuroPMC
==Nivolumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Rizvi et al. 2015 (CheckMate 063) 	2012-2013 	Phase 2 	 	
Brahmer et al. 2015 (CheckMate 017)	2012-10 to 2013-12 	Phase 3 (E-RT-switch-ooc)	Docetaxel 	Longer OS (primary endpoint)Median OS: 9 vs 6 mo(HR 0.59, 95% CI 0.44-0.79)
Gettinger et al. 2021 (Lung-MAP) 	2015-2018 	Phase 3 (C) 	Ipilimumab & Nivolumab	Did not meet primary endpoint of OSMedian OS: 11 vs 10 mo(HR 1.15, 95% CI 0.86-1.52)
Note: On 2016-09-13 the FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.
====Prior treatment criteria====
*CheckMate 017: One prior platinum-containing regimen
*Lung-MAP: Previously treated with platinum-doublet chemotherapy, no prior immunotherapy
====Immunotherapy====
*Nivolumab (Opdivo) 3 mg/kg IV once on day 1
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 Mar;16(3):257-65. Epub 2015 Feb 20. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC 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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 link to PMC article EuroPMC
##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 EuroPMC
##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 link to PMC article EuroPMC
#Lung-MAP: Gettinger SN, Redman MW, Bazhenova L, Hirsch FR, Mack PC, Schwartz LH, Bradley JD, Stinchcombe TE, Leighl NB, Ramalingam SS, Tavernier SS, Yu H, Unger JM, Minichiello K, Highleyman L, Papadimitrakopoulou VA, Kelly K, Gandara DR, Herbst RS. Nivolumab Plus Ipilimumab vs Nivolumab for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer: The Lung-MAP S1400I Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1368-1377. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT02785952
##HRQoL analysis: Unger JM, Qian L, Redman MW, Tavernier SS, Minasian L, Sigal EV, Papadimitrakopoulou VA, Leblanc M, Cleeland CS, Dzingle SA, Summers TJ, Chao H, Madhusudhana S, Villaruz L, Crawford J, Gray JE, Kelly KL, Gandara DR, Bazhenova L, Herbst RS, Gettinger SN, Moinpour CM. Quality-of-life outcomes and risk prediction for patients randomized to nivolumab plus ipilimumab vs nivolumab on LungMAP-S1400I. J Natl Cancer Inst. 2023 Apr;115(4):437-446. link to original article link to EuroPMC
Category:Non-small cell lung cancer regimens
Category:Histology-specific pages
Category:Non-small cell lung cancers