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{8c47d8678e25461b91da5583f8b1bf4a,
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 -