Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC

IntroductionIn 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 long-term outcomes from this study.MethodsPatients previously untreated NSCLC without sensitizing EGFR or ALK alterations were randomly assigned 1:1 to receive open-label pemetrexed 500 mg/m2 carboplatin at area under concentration-time curve 5 mg/mL/min (four cycles) 200 mg (up 2 years), optional maintenance, each administered every 3 weeks. Eligible patients could crossover arm monotherapy after progression. Responses assessed per Response Evaluation Criteria Solid Tumors version 1.1.ResultsAfter median time 49.4 months randomization data cutoff, (58% 33%) (median: 24.5 9.9 mo; hazard ratio: 0.54; 95% confidence interval: 0.35‒0.83) remained combination (n = 60) 63), regardless programmed death ligand 1 status. Median overall was 34.5 21.1 (hazard 0.71; 0.45‒1.12), despite a 70% anti‒programmed (ligand) therapy. Among 12 who completed years pembrolizumab, 92% alive cutoff; estimated 3-year duration 100%. Grade treatment-related adverse events occurred 39% receiving 31% chemotherapy.ConclusionsFirst-line continued show NSCLC, durable clinical benefit No new safety signals observed longer follow-up.