Pembrolizumab (pembro) plus chemotherapy as front-line therapy for advanced NSCLC: KEYNOTE-021 cohorts A-C.

Abstract

9016 Background: The anti–PD-1 antibody pembro exhibits robust antitumor activity in patients (pts) with advanced NSCLC. In cohorts A-C of KEYNOTE-021 (NCT02039674), we evaluated the efficacy and safety of pembro + various chemotherapy combinations in advanced NSCLC. Methods: Chemotherapy-naive, advanced, EGFR/ALK (-) NSCLC pts, PS 0 or 1, were randomly assigned to pembro 2 or 10 mg/kg Q3W plus either carboplatin AUC 6 + paclitaxel 200 mg/m2 (A, any histology), carboplatin AUC 6 + paclitaxel 200 mg/m2 + bevacizumab (BEV) 15 mg/kg (B, nonsquamous), or carboplatin AUC 5 + pemetrexed (PEM) 500 mg/m2(C, nonsquamous) for 4 cycles followed by maintenance pembro (A), pembro + BEV (B), or pembro + PEM (C). Response was assessed every 6 wk by central imaging vendor. Results: As of Dec 16, 2015, 74 pts (25 in A, 25 in B, and 24 in C) had been treated; median follow-up duration was 12 mo (A = 13; B = 9; C = 16). 1 DLT occurred in cycle 1 (gr 3 rash, C). Gr 3-4 treatment-related AEs occurred in 36%, 46%, and 42% of pts, in cohorts A, B, and C, respectively, most commonly AST elevation (n = 3 in C), anemia (n = 2 each in A and C), neutropenia (n = 2 each in A and B), and febrile neutropenia (n = 2 each in A and B). 1 treatment-related death occurred (B, pericardial effusion). Efficacy is shown by cohort and by PD-L1 status and pembro dose with cohorts combined. At data cutoff, 24 pts remained on treatment. Conclusions: Pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in treatment-naive advanced NSCLC. Longitudinal follow-up is ongoing. A randomized phase 3 study evaluating pemetrexed/platinum +/- pembro is currently recruiting. Clinical trial information: NCT02039674. N ORR (confirmed) Survival, median (95% CI), mo n (%) 95% CI PFS OS Total 74 42 (57) 45-68 10 (6-NR) NR (17-NR) Cohort A 25 13 (52) 31-72 10 (4-NR) NR (11-NR) Cohort B 25 12 (48) 28-69 NR (4.1-NR) NR (NR-NR) Cohort C 24 17 (71) 49-87 10 (6-15) NR (14-NR) PD-L1 25 15 (60) 39-79 15 (6-15) 17 (15-NR) TPS ≥50% TPS ≥1%-49% 26 14 (54) 33-73 14 (6-NR) NR (14-NR) TPS <1% 22 12 (55) 32-76 6 (4-NR) 11 (7-NR) Pembro dose 2 mg/kg 37 23 (62) 45-78 NR (6-NR) NR (15-NR) 10 mg/kg 37 19 (51) 34-68 7 (4-10) NR (10-NR) NR = not reached; TPS = tumor proportion score.