Related Experiment Video
Updated: Nov 20, 2025
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the
David A Reardon1, Tae Min Kim2, Jean-Sebastien Frenel3
1Dana-Farber Cancer Institute, Boston, Massachusetts.
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 (ClinicalTrials.gov 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.
Insights
Pembrolizumab immunotherapy showed antitumor activity in recurrent glioblastoma patients with PD-L1 positive tumors. This treatment demonstrated manageable toxicity, suggesting potential for future combination therapies in glioblastoma treatment.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Clinical Trials
Background:
- Recurrent glioblastoma treatment options are limited.
- Investigating anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, for recurrent glioblastoma.
- Focus on programmed death ligand 1 (PD-L1)-positive tumors.
Purpose of the Study:
- Evaluate the antitumor activity and safety of pembrolizumab in recurrent glioblastoma.
- Assess overall response rate (ORR) in PD-L1-positive patients.
- Explore potential correlations with biomarkers.
Main Methods:
- Phase 1b, multicohort study (KEYNOTE-028) enrolling adult patients with PD-L1-positive recurrent glioblastoma.
- Pembrolizumab administered at 10 mg/kg every 2 weeks for up to 2 years.
- Primary endpoint: investigator-assessed ORR; secondary: safety, progression-free survival (PFS), overall survival (OS).
Main Results:
- Overall response rate (ORR) was 8% (2 partial responses) among 26 patients after median 14-month follow-up.
- Median PFS was 2.8 months; 6-month PFS rate was 37.7%.
- Median OS was 13.1 months; 12-month OS rate was 58%. Treatment-related adverse events (AEs) in 73%, grade 3/4 AEs in 19%.
Conclusions:
- Pembrolizumab monotherapy showed durable antitumor activity in a subset of recurrent glioblastoma patients.
- The treatment was associated with manageable toxicity.
- Future research should explore pembrolizumab combination regimens to improve outcomes.
