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
Journal of Thoracic Oncology
Journal Volume
14
Journal Issue
1
Pages
124-129
Date Issued
2019
Author(s)
Borghaei H
Langer C.J
Gadgeel S
Papadimitrakopoulou V.A
Patnaik A
Powell S.F
Gentzler R.D
Martins R.G
Stevenson J.P
Jalal S.I
Panwalkar A
Gubens M
Sequist L.V
Awad M.M
Fiore J
Saraf S
Keller S.M
Gandhi L.
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. ? 2018 International Association for the Study of Lung Cancer
Subjects
Chemotherapy; Combination therapy; Nonsquamous non?small cell lung cancer; Pembrolizumab
SDGs
Other Subjects
alanine aminotransferase; aspartate aminotransferase; carboplatin; creatinine; pembrolizumab; pemetrexed; antineoplastic agent; carboplatin; monoclonal antibody; pembrolizumab; pemetrexed; advanced cancer; alanine aminotransferase blood level; anemia; Article; aspartate aminotransferase blood level; cancer growth; cancer staging; cohort analysis; colitis; constipation; controlled study; creatinine blood level; decreased appetite; diarrhea; drug efficacy; drug safety; dysgeusia; fatigue; follow up; human; hyperthyroidism; hypothyroidism; infusion related reaction; lacrimation disorder; major clinical study; multiple cycle treatment; nausea; neutrophil count; non small cell lung cancer; open study; overall survival; phase 1 clinical trial; phase 2 clinical trial; pneumonia; priority journal; progression free survival; pruritus; rash; side effect; skin toxicity; vomiting; female; lung tumor; male; mortality; non small cell lung cancer; pathology; survival rate; time factor; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Pemetrexed; Progression-Free Survival; Survival Rate; Time Factors
Publisher
Elsevier Inc
Type
journal article