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

Conference Correspondent - ASCO 2016

The anti–PD-1 antibody pembrolizumab (pembro) has been shown to exhibit robust antitumor activity in patients with advanced non–small-cell lung cancer (NSCLC) in the KEYNOTE-001 and KEYNOTE-010 studies.1,2 In cohorts A-C of KEYNOTE-021, Gadgeel and coworkers evaluated the efficacy and safety of pembro + various chemotherapy combinations in advanced NSCLC.3 In this study, chemotherapy-naive, advanced, EGFR/ALK (-) NSCLC patients were randomly assigned to pembro 2 mg/kg or 10 mg/kg every 3 weeks 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 weeks by a central imaging vendor. As of December 16, 2015, 74 patients (25 in A, 25 in B, and 24 in C) had been treated, with a median follow-up duration of 12 months (A = 13; B = 9; C = 16). Grade 3-4 treatment-related adverse events occurred in 36%, 46%, and 42% of patients in cohorts A, B, and C, respectively, most commonly liver enzyme elevation, anemia, neutropenia, and febrile neutropenia. One treatment-related death occurred (in group B, due to a pericardial effusion). Efficacy is shown in the Table by cohort and by PD-L1 status and pembro dose with cohorts combined. This study showed that pembro in combination with standard chemotherapy regimens is feasible and yields substantial clinical efficacy regardless of pembro dose or PD-L1 status in patients with treatment-naive advanced NSCLC. A randomized phase 3 study evaluating PEM/platinum ± pembro is currently recruiting.Article3_Table
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  1. Garon EB, et al. N Engl J Med. 2015;372:2018-2028.
  2. Herbst RS, et al. Lancet. 2016;387:1540-1550.
  3. Gadgeel SM, et al. ASCO 2016. Abstract 9016.