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

Cancer. 2021 May 15;127(10):1620-1629. doi: 10.1002/cncr.33378. Epub 2021 Jan 26.


Background: Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD-L1)-positive, recurrent glioblastoma.

Methods: Adult patients with PD-L1-positive tumors were enrolled in the recurrent glioblastoma cohort of the multicohort, phase 1b KEYNOTE-028 study ( identifier, NCT02054806) and received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years. The primary endpoint was investigator-assessed overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Archival tumor samples were assessed for PD-L1 expression levels (prospectively) and T-cell-inflamed gene expression profile score (retrospectively).

Results: After a median follow-up of 14 months (range, 2-55 months) among the 26 enrolled patients, the overall response rate was 8% (95% CI, 1%-26%). Two partial responses, lasting 8.3 and 22.8 months, occurred. Progression-free survival (median, 2.8 months; 95% CI, 1.9-8.1 months) rate at 6 months was 37.7%, and the overall survival (median, 13.1 months; 95% CI, 8.0-26.6 months) rate at 12 months was 58%. Correlation of therapeutic benefit to level of PD-L1 expression, gene expression profile score, or baseline steroid use could not be established. Treatment-related adverse events occurred in 19 patients (73%), and 5 patients experienced grade 3 or 4 events (there were no grade 5 events). Immune-mediated adverse events and infusion reactions occurred in 7 patients (27%).

Conclusions: Pembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with manageable toxicity in this small, signal-finding, recurrent glioblastoma cohort. Future studies evaluating rationally designed pembrolizumab combination regimens may improve outcomes in patients with recurrent glioblastoma.

Keywords: glioblastoma; immunotherapy; pembrolizumab; programmed death ligand 1; treatment outcomes.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological / therapeutic use
  • B7-H1 Antigen* / metabolism
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Humans
  • Neoplasm Recurrence, Local* / drug therapy
  • Neoplasm Recurrence, Local* / pathology
  • Retrospective Studies
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • pembrolizumab

Associated data