Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC
Journal
Journal of Thoracic Oncology
Journal Volume
16
Journal Issue
1
Pages
162-168
Date Issued
2021
Author(s)
Awad M.M.
Gadgeel S.M.
Borghaei H.
Patnaik A.
Powell S.F.
Gentzler R.D.
Martins R.G.
Stevenson J.P.
Altan M.
Jalal S.I.
Panwalkar A.
Gubens M.
Sequist L.V.
Saraf S.
Zhao B.
Piperdi B.
Langer C.J.
Abstract
Introduction: In cohort G of KEYNOTE-021 (NCT02039674), first-line pembrolizumab plus pemetrexed-carboplatin significantly improved the objective response rate and progression-free survival versus chemotherapy alone with manageable toxicity in advanced nonsquamous NSCLC. We report the long-term outcomes from this study. Methods: Patients with previously untreated advanced nonsquamous NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m2 plus carboplatin at area under the concentration-time curve of 5 mg/mL/min (four cycles) with or without pembrolizumab 200 mg (up to 2 years), with optional pemetrexed maintenance, each administered every 3 weeks. Eligible patients could crossover from the chemotherapy arm to pembrolizumab monotherapy after progression. Responses were assessed per the Response Evaluation Criteria in Solid Tumors version 1.1. Results: After the median time of 49.4 months from randomization to data cutoff, objective response rate (58% versus 33%) and progression-free survival (median: 24.5 versus 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35?0.83) remained improved with pembrolizumab combination (n = 60) versus chemotherapy (n = 63), regardless of programmed death ligand 1 status. Median overall survival was 34.5 versus 21.1 months (hazard ratio: 0.71; 95% confidence interval: 0.45?1.12), despite a 70% crossover rate from chemotherapy alone to anti?programmed death (ligand) 1 therapy. Among the 12 patients who completed 2 years of pembrolizumab, 92% were alive at data cutoff; the estimated 3-year duration of response rate was 100%. Grade 3 to 5 treatment-related adverse events occurred in 39% of patients receiving pembrolizumab combination and 31% receiving chemotherapy. Conclusions: First-line pembrolizumab plus pemetrexed-carboplatin continued to show improved response and survival versus chemotherapy alone in advanced nonsquamous NSCLC, with durable clinical benefit in patients who completed 2 years of therapy. No new safety signals were observed with longer follow-up. ? 2020 International Association for the Study of Lung Cancer
Subjects
Advanced nonsquamous non?small-cell lung cancer; Chemotherapy; First-line therapy; Long-term survival; Pembrolizumab
SDGs
Other Subjects
carboplatin; pembrolizumab; pemetrexed; programmed death 1 ligand 1; antineoplastic agent; carboplatin; monoclonal antibody; pembrolizumab; pemetrexed; adult; advanced cancer; aged; ALK gene; area under the curve; Article; cancer chemotherapy; cancer growth; cohort analysis; controlled study; EGFR gene; female; gene; gene mutation; human; maintenance therapy; major clinical study; male; multiple cycle treatment; non small cell lung cancer; open study; overall survival; phase 2 clinical trial; priority journal; progression free survival; randomized controlled trial; treatment outcome; treatment response; unspecified side effect; lung tumor; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Humans; Lung Neoplasms; Pemetrexed
Publisher
Elsevier Inc.
Type
journal article