Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial.

摘要: Background Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, in programmed ligand (PD-L1)-positive, glioblastoma. Methods Adult patients with PD-L1-positive tumors were enrolled cohort multicohort, phase 1b KEYNOTE-028 study (ClinicalTrials.gov identifier, NCT02054806) received pembrolizumab 10 mg/kg every 2 weeks up to years. primary endpoint was investigator-assessed overall response rate according Response Evaluation Criteria Solid Tumors, version 1.1. Archival tumor samples assessed PD-L1 expression levels (prospectively) T-cell-inflamed gene profile score (retrospectively). Results After a median follow-up 14 months (range, 2-55 months) among 26 patients, 8% (95% CI, 1%-26%). Two partial responses, lasting 8.3 22.8 months, occurred. Progression-free survival (median, 2.8 months; 95% 1.9-8.1 at 6 37.7%, 13.1 8.0-26.6 12 58%. Correlation therapeutic benefit level expression, score, or baseline steroid use could not be established. Treatment-related adverse events occurred 19 (73%), 5 experienced grade 3 4 (there no events). Immune-mediated infusion reactions 7 (27%). Conclusions Pembrolizumab monotherapy demonstrated durable subset manageable toxicity this small, signal-finding, cohort. Future studies evaluating rationally designed combination regimens may improve outcomes