Pembrolizumab (pembro; MK-3475) plus platinum doublet chemotherapy (PDC) as front-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 Cohorts A and C.

Abstract

8031 Background: As monotherapy, the anti–PD-1 antibody pembro has shown robust antitumor activity in advanced NSCLC patients (pts). KEYNOTE-021 evaluated the safety, tolerability, and clinical activity of pembro + PDC for treatment-naive advanced NSCLC. Methods: Pts with stage IIIB/IV NSCLC and no prior systemic therapy were randomized 1:1 to pembro 2 or 10 mg/kg Q3W plus carboplatin AUC 6 + paclitaxel 200 mg/m2 (cohort A; any histology) or carboplatin AUC 5 + pemetrexed 500 mg/m2 (cohort C; nonsquamous without EGFR sensitizing mutation or ALK translocation only). Pts received pembro + PDC for 4 cycles followed by pembro maintenance in A and pembro + pemetrexed in C. The dose-limiting toxicity (DLT) observation window was the first 3 wk after initial dosing. Key eligibility criteria included ECOG PS 0-1, measurable disease, and adequate tumor sample for PD-L1 assessment. Response was assessed every 6 wk until confirmed progression (RECIST v1.1, investigator review). Results: As of Dec 2014, 44 pts (20 in cohort A and 24 in cohort C) were treated. One DLT was reported (hospitalization for gr 3 rash, C [pembro 10 mg/kg]). Gr 3-4 treatment-related AE rate was 27% (15% in A, 38% in C); AEs were reversible transaminase elevation (n = 3 in C), anemia (n = 1 in A, 2 in C), rash (n = 1 in A, 1 in C), and colitis (n = 2 in C); no gr 3-4 febrile neutropenia was observed. One patient in C discontinued due to treatment-related gr 3 rash. No treatment-related deaths have occurred. Preliminary ORR (confirmed and unconfirmed) is 30% in A and 58% in C (Table). At the time of analysis, 16 pts in A and 21 pts in C remained on treatment. Conclusions: These data suggest that pembro + PDC has a reasonable safety profile and provides antitumor activity as front-line therapy for stage IIIB/IV NSCLC. Based on the promising ORR observed for pembro + carboplatin and pemetrexed, this combination is being evaluated in a larger cohort. Clinical trial information: NCT02039674. A (carboplatin/paclitaxel) C (carboplatin/pemetrexed) Pembro 10 n = 10 Pembro 2 n = 10 Pembro 10 n = 12 Pembro 2 n = 12 ORR (all PR) 3 (30%) 3 (30%) 8 (67%) 6 (50%) SD 3 (30%) 5 (50%) 4 (33%) 5 (42%) DCR (PR + SD) 6 (60%) 8 (80%) 12 (100%) 11 (92%) PD 3 (30%) 1 (10%) 0 0 No assessment 1 (10%) 1 (10%) 0 1 (8%)

Keywords

Affiliated Institutions

• Cleveland Clinic US
• Merck & Co., Inc., Rahway, NJ, USA (United States) US
• Massachusetts General Hospital US
• Fox Chase Cancer Center US
• Dana-Farber Cancer Institute US
• The Barbara Ann Karmanos Cancer Institute US
• The University of Texas MD Anderson Cancer Center US
• South Texas Accelerated Research Therapeutics US
• University of California, San Francisco US
• National Taiwan University Hospital TW

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