FCCC LOGO Faculty Publications
Awad MM , Gadgeel SM , Borghaei H , Patnaik A , Yang JC , Powell SF , Gentzler RD , Martins RG , Stevenson JP , Altan M , Jalal SI , Panwalkar A , Gubens M , Sequist LV , Saraf S , Zhao B , Piperdi B , Langer CJ
Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC
J Thorac Oncol. 2021 jan;16(1) :162-168
Back to previous list
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/m(2) 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.
1556-1380 Awad, Mark M Gadgeel, Shirish M Borghaei, Hossein Patnaik, Amita Yang, James Chih-Hsin Powell, Steven F Gentzler, Ryan D Martins, Renato G Stevenson, James P Altan, Mehmet Jalal, Shadia I Panwalkar, Amit Gubens, Matthew Sequist, Lecia V Saraf, Sanatan Zhao, Bin Piperdi, Bilal Langer, Corey J Journal Article United States J Thorac Oncol. 2021 Jan;16(1):162-168. doi: 10.1016/j.jtho.2020.09.015. Epub 2020 Oct 15.