Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non–small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. (November 2018)

• Record Type: Journal Article
• Authors: Gadgeel, Shirish M.; Stevenson, James P.; Langer, Corey J.; Gandhi, Leena; Borghaei, Hossein; Patnaik, Amita; Villaruz, Liza C.; Gubens, Matthew; Hauke, Ralph; Yang, James Chih-Hsin; Sequist, Lecia V.; Bachman, Robert; Saraf, Sanatan; Raftopoulos, Harry; Papadimitrakopoulou, Vassiliki
• Is Part Of: Lung cancer. Volume 125(2018)
• Page Start: 273
• Page End: 281
• Publication Date: 2018-11
• Subjects: AUC area under the serum concentration-time curve -- DLT dose-limiting toxicity -- PD-1 programmed death 1 -- PD-L1 programmed death ligand 1 -- SLD sum of longest diameters -- TPS tumor proportion score; Carcinoma -- Non–small-cell lung -- Pembrolizumab -- Drug therapy -- Combination -- Antineoplastic agents -- Bevacizumab; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2018.08.019
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: KEYNOTE-021 A-C evaluated pembrolizumab + platinum chemotherapy in advanced NSCLC. No dose-limiting toxicity occurred in any cohort at pembrolizumab 2 or 10 mg/kg. Evidence of antitumor activity in all 3 cohorts at both pembrolizumab doses. Pembrolizumab + platinum chemotherapy is a feasible front-line treatment strategy. Abstract: Objectives: Platinum-based chemotherapy for advanced non–small-cell lung cancer (NSCLC) has modest benefit overall, but has the potential to amplify immune responses. In cohorts A-C of the multicohort phase 1/2 study KEYNOTE-021 (Clinicaltrials.gov, NCT02039674), we evaluated combinations of platinum-doublet chemotherapy with the anti–programmed death 1 monocloncal antibody pembrolizumab. Materials and methods: Patients with previously untreated, advanced NSCLC without EGFR / ALK aberrations were randomized to pembrolizumab 2 or 10 mg/kg Q3W plus carboplatin area under the serum concentration-time curve (AUC) 6 mg/mL/min plus paclitaxel 200 mg/m 2 (cohort A, any histology), carboplatin AUC 6 mg/mL/min plus paclitaxel 200 mg/m 2 plus bevacizumab 15 mg/kg (cohort B, non-squamous), or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m 2 (cohort C, non-squamous) for 4 cycles followed by maintenance pembrolizumab (cohort A), pembrolizumab plus bevacizumab (cohort B), or pembrolizumab plus pemetrexed (cohort C). Response was assessed by blinded independent central review. Results: Overall, 74 patients were randomized; median follow-up was 21.4, 16.4, and 17.4 months in cohorts A, B, and C, respectively. No dose-limiting toxicities occurred in any cohort at either pembrolizumab dose. Most frequent treatment-related adverse events (AEs) were alopecia, fatigue, and nausea. Treatment-related grade 3/4 AEs occurred in 40%, 42%, and 46% of patients in cohorts A, B, and C, respectively; AEs with possible immune etiology occurred in 24%, 50%, and 38% of patients, respectively. Objective response rates were 48%, 56%, and 75% in cohorts A, B, and C, respectively. Conclusion: Pembrolizumab in combination with carboplatin-paclitaxel and with pemetrexed-carboplatin yielded encouraging antitumor activity and toxicity consistent with known toxicities of platinum-based chemotherapy or pembrolizumab monotherapy.