KEYNOTE‐025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1–positive advanced non–small‐cell lung cancer

Abstract

Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD‐1), has been shown to improve overall survival (OS) in patients with previously treated advanced non–small‐cell lung cancer (NSCLC) with programmed death ligand 1 (PD‐L1) tumor proportion score (TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE‐025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD‐L1 TPS ≥1% and had received ≥1 platinum‐doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD‐L1 TPS ≥1% and the objective response rate (ORR) per RECIST version 1.1 in patients with PD‐L1 TPS ≥50%. Thirty‐eight patients were enrolled and received ≥1 pembrolizumab dose. The median (range) age was 66.0 (41‐78) years, and 61% had received ≥2 prior systemic therapies. Eleven patients (29%) experienced grade 3‐5 treatment‐related adverse events (AE); 9 patients (24%) experienced immune‐mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD‐L1 TPS ≥50% (n = 11), ORR was 27% (95% CI, 6‐61). Among evaluable patients with PD‐L1 TPS ≥1% (n = 37), ORR was 22% (95% CI, 10‐38). Median (95% CI) progression‐free survival and OS were 3.9 (2.0‐6.2) months and 19.2 (8.0‐26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD‐L1–expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE‐010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.)

Pembrolizumab monotherapy in Japanese patients with advanced ovarian cancer: Subgroup analysis from the KEYNOTE‐100

“…Although no cases of pneumonitis were reported in the Japanese subgroup, it is a life‐threatening immune‐mediated AE that requires immediate action by healthcare providers. The results from the phase 1b KEYNOTE‐025 study (ClinicalTrials.gov identifier, NCT02007070) regarding efficacy and safety of pembrolizumab in 38 Japanese patients with previously treated PD‐L1‐expressing advanced NSCLC were recently reported . The most common immune‐mediated AE in this study was pneumonitis (n = 4, 10.5%), including 1 fatal case (the remaining three cases resolved).…”

Different patterns of treatment‐related adverse events of programmed cell death‐1 and its ligand‐1 inhibitors in different cancer types: A meta‐analysis and systemic review of clinical trials

“…The process of study selection was illustrated in Figure 1. Ninety‐six clinical trials were finally selected for meta‐analysis, after being screened and assessed 11–106 . We focused on cancer types with no less than 3 relative clinical trials, including lung cancer (small cell and non–small cell; n = 20), melanoma ( n = 18), urothelial carcinoma ( n = 16), renal cell cancer ( n = 5), digestive system cancers (esophageal/gastric/colorectal/anal/liver; n = 15), head and neck squamous cell carcinoma (including nasopharyngeal cancer; n = 9), breast cancer ( n = 4), gynecological cancer (ovarian/cervical/endometrial; n = 5) and malignant mesothelioma ( n = 4).…”

Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

“…Compared with clinical trials (2.8-6.6%), the occurrence of pneumonitis in our study was higher, at 14.3% ( 10 – 13 ). Reports suggest that the occurrence of pneumonitis may be higher in Japanese patients receiving ICI monotherapy; this suggests that the incidence of pneumonitis may be higher in Japanese patients receiving immunotherapy plus chemotherapy ( 23 , 24 ).…”