Phase 1 study of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC
Takayasu Kurata, Kazuhiko Nakagawa, Miyako Satouchi, Takashi Seto, Takeshi Sawada, Shirong Han, Masae Homma, Kazuo Noguchi, Naoyuki Nogami, Takayasu Kurata, Kazuhiko Nakagawa, Miyako Satouchi, Takashi Seto, Takeshi Sawada, Shirong Han, Masae Homma, Kazuo Noguchi, Naoyuki Nogami
Abstract
Introduction: Pembrolizumab plus chemotherapy significantly improved outcomes over chemotherapy alone as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC) in phase 3 international trials. In the phase 1 KEYNOTE-011 study (parts B and C), we evaluated the safety/activity of pembrolizumab plus chemotherapy as first-line treatment in Japanese patients with advanced NSCLC.
Methods: Eligible patients received 4 cycles (every 3 weeks) of pembrolizumab 200 mg plus chemotherapy (cisplatin 75 mg/m2/carboplatin area under the curve [AUC] 5 mg/mL/min and pemetrexed 500 mg/m2 in part B [nonsquamous]; carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m2/nab-paclitaxel 100 mg/m2 (weekly) in part C [squamous]), followed by maintenance pembrolizumab (and pemetrexed, part B). The primary endpoint was incidence of dose-limiting toxicities (DLTs) during the first 3 weeks of treatment. Overall response rate (ORR; RECIST v1.1 by central review) was exploratory.
Results: In part B (median follow-up, 16.0 months; n = 12) 1 DLT occurred (grade 4 hyponatremia). Grade ≥3 treatment-related adverse events (AEs) occurred in 9 patients (75%). Two patients had grade 5 treatment-related AEs (pneumonitis and interstitial lung disease). In part C (median follow-up, 9.9 months; n = 14), 2 DLTs occurred (both grade 3 febrile neutropenia). Grade ≥3 treatment-related AEs occurred in 11 patients (79%); none were fatal. ORR was 73% in part B and 50% in part C, irrespective of PD-L1 status.
Conclusion: Safety results show first-line pembrolizumab plus chemotherapy is feasible in Japanese patients with advanced NSCLC. Antitumor activity was observed irrespective of PD-L1 status and was comparable to that in international studies.
Trial register: ClinicalTrials.gov, NCT01840579.
Keywords: Antineoplastic agents; Antitumor activity; Japan; Non–small-cell lung carcinoma; Programmed death ligand 1.
Copyright © 2021 Merck Sharp & Dohme Corp., The Author(s). Published by Elsevier Ltd.. All rights reserved.
Source: PubMed