24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer

Hossein Borghaei, Corey J. Langer, Shirish Gadgeel, Vassiliki A. Papadimitrakopoulou, Amita Patnaik, Steven F. Powell, Ryan D. Gentzler, Renato G. Martins, James P. Stevenson, Shadia I. Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V. Sequist, Mark M. Awad, Joseph Fiore, Sanatan Saraf, Steven M. Keller, Leena Gandhi

Research output: Contribution to journalArticle

  • 1 Citations

Abstract

Introduction: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.

LanguageEnglish (US)
JournalJournal of Thoracic Oncology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Pemetrexed
Carboplatin
Non-Small Cell Lung Carcinoma
Survival
Therapeutics
Confidence Intervals
Disease-Free Survival
pembrolizumab

Keywords

  • Chemotherapy
  • Combination therapy
  • Nonsquamous non‒small cell lung cancer
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

24-Month Overall Survival from KEYNOTE-021 Cohort G : Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer. / Borghaei, Hossein; Langer, Corey J.; Gadgeel, Shirish; Papadimitrakopoulou, Vassiliki A.; Patnaik, Amita; Powell, Steven F.; Gentzler, Ryan D.; Martins, Renato G.; Stevenson, James P.; Jalal, Shadia I.; Panwalkar, Amit; Chih-Hsin Yang, James; Gubens, Matthew; Sequist, Lecia V.; Awad, Mark M.; Fiore, Joseph; Saraf, Sanatan; Keller, Steven M.; Gandhi, Leena.

In: Journal of Thoracic Oncology, 01.01.2018.

Research output: Contribution to journalArticle

Borghaei, H, Langer, CJ, Gadgeel, S, Papadimitrakopoulou, VA, Patnaik, A, Powell, SF, Gentzler, RD, Martins, RG, Stevenson, JP, Jalal, SI, Panwalkar, A, Chih-Hsin Yang, J, Gubens, M, Sequist, LV, Awad, MM, Fiore, J, Saraf, S, Keller, SM & Gandhi, L 2018, '24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer' Journal of Thoracic Oncology. https://doi.org/10.1016/j.jtho.2018.08.004
Borghaei, Hossein ; Langer, Corey J. ; Gadgeel, Shirish ; Papadimitrakopoulou, Vassiliki A. ; Patnaik, Amita ; Powell, Steven F. ; Gentzler, Ryan D. ; Martins, Renato G. ; Stevenson, James P. ; Jalal, Shadia I. ; Panwalkar, Amit ; Chih-Hsin Yang, James ; Gubens, Matthew ; Sequist, Lecia V. ; Awad, Mark M. ; Fiore, Joseph ; Saraf, Sanatan ; Keller, Steven M. ; Gandhi, Leena. / 24-Month Overall Survival from KEYNOTE-021 Cohort G : Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer. In: Journal of Thoracic Oncology. 2018.
@article{663b8d3937b3468b8a2c54b9b4b4300c,
title = "24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non–Small Cell Lung Cancer",
abstract = "Introduction: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95{\%} confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7{\%} with pembrolizumab plus PC versus 30.2{\%} with PC alone (estimated difference 26.4{\%} [95{\%} CI: 8.9{\%}‒42.4{\%}, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95{\%} CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95{\%} CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27{\%} in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.",
keywords = "Chemotherapy, Combination therapy, Nonsquamous non‒small cell lung cancer, Pembrolizumab",
author = "Hossein Borghaei and Langer, {Corey J.} and Shirish Gadgeel and Papadimitrakopoulou, {Vassiliki A.} and Amita Patnaik and Powell, {Steven F.} and Gentzler, {Ryan D.} and Martins, {Renato G.} and Stevenson, {James P.} and Jalal, {Shadia I.} and Amit Panwalkar and {Chih-Hsin Yang}, James and Matthew Gubens and Sequist, {Lecia V.} and Awad, {Mark M.} and Joseph Fiore and Sanatan Saraf and Keller, {Steven M.} and Leena Gandhi",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.jtho.2018.08.004",
language = "English (US)",
journal = "Journal of Thoracic Oncology",
issn = "1556-0864",
publisher = "International Association for the Study of Lung Cancer",

}

TY - JOUR

T1 - 24-Month Overall Survival from KEYNOTE-021 Cohort G

T2 - Journal of Thoracic Oncology

AU - Borghaei, Hossein

AU - Langer, Corey J.

AU - Gadgeel, Shirish

AU - Papadimitrakopoulou, Vassiliki A.

AU - Patnaik, Amita

AU - Powell, Steven F.

AU - Gentzler, Ryan D.

AU - Martins, Renato G.

AU - Stevenson, James P.

AU - Jalal, Shadia I.

AU - Panwalkar, Amit

AU - Chih-Hsin Yang, James

AU - Gubens, Matthew

AU - Sequist, Lecia V.

AU - Awad, Mark M.

AU - Fiore, Joseph

AU - Saraf, Sanatan

AU - Keller, Steven M.

AU - Gandhi, Leena

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.

AB - Introduction: Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the primary analysis (median follow-up time 10.6 months), pembrolizumab significantly improved objective response rate (ORR) and progression-free survival (PFS); the hazard ratio (HR) for overall survival (OS) was 0.90 (95% confidence interval [CI]: 0.42‒1.91). Herein, we present an updated analysis. Methods: A total of 123 patients with previously untreated stage IIIB/IV nonsquamous NSCLC without EGFR and/or ALK receptor tyrosine kinase gene (ALK) aberrations were randomized 1:1 to four cycles of PC with or without pembrolizumab, 200 mg every 3 weeks. Pembrolizumab treatment continued for 2 years; maintenance pemetrexed was permitted in both groups. Eligible patients in the PC-alone group with radiologic progression could cross over to pembrolizumab monotherapy. p Values are nominal (one-sided p < 0.025). Results: As of December 1, 2017, the median follow-up time was 23.9 months. The ORR was 56.7% with pembrolizumab plus PC versus 30.2% with PC alone (estimated difference 26.4% [95% CI: 8.9%‒42.4%, p = 0.0016]). PFS was significantly improved with pembrolizumab plus PC versus PC alone (HR = 0.53, 95% CI: 0.33‒0.86, p = 0.0049). A total of 41 patients in the PC-alone group received subsequent anti‒programmed death 1/anti‒programmed death ligand 1 therapy. The HR for OS was 0.56 (95% CI: 0.32‒0.95, p = 0.0151). Forty-one percent of patients in the pembrolizumab plus PC group and 27% in the PC-alone group had grade 3 to 5 treatment-related adverse events. Conclusions: The significant improvements in PFS and ORR with pembrolizumab plus PC versus PC alone observed in the primary analysis were maintained, and the HR for OS with a 24-month median follow-up was 0.56, favoring pembrolizumab plus PC.

KW - Chemotherapy

KW - Combination therapy

KW - Nonsquamous non‒small cell lung cancer

KW - Pembrolizumab

UR - http://www.scopus.com/inward/record.url?scp=85053358614&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053358614&partnerID=8YFLogxK

U2 - 10.1016/j.jtho.2018.08.004

DO - 10.1016/j.jtho.2018.08.004

M3 - Article

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

ER -