Re-Irradiation Plus Pembrolizumab: A Phase II Study for Patients with Recurrent Glioblastoma
Phase 2 or 3 results paper on Pembrolizumab in Glioma & glioblastoma, in Clinical Cancer Research (2025), one of the most cited Europe PMC records with Pembrolizumab in its title.
Overview
Purpose: Radiotherapy may enhance antitumor immune responses by several mechanisms, including induction of immunogenic cell death. We performed a phase 2 study of pembrolizumab with re-irradiation in patients with recurrent glioblastoma.
Patients and methods: Sixty patients with recurrent glioblastoma received pembrolizumab with re-irradiation alone (cohort A, bevacizumab-naïve; n = 30) or with bevacizumab continuation (cohort B, n = 30). Dual primary endpoints, including the overall response rate and overall survival (OS) at either 12 (OS-12; cohort A) or 6 months (OS-6; cohort B), were assessed per cohort relative to historic benchmarks. Paired paraffin-embedded formalin-fixed tumor samples were assessed for immunologic biomarkers by IHC using digital quantification and co-detection-by-indexing (CODEX).
Results: Study therapy was well tolerated, with most toxicities being grade ≤3. For cohort B, the primary endpoint of OS-6 was achieved (57%); however, survival was not improved for cohort A patients. The overall response rate was 3.3% and 6.7% for cohorts A and B, respectively. CODEX analysis of paired tumor samples from five patients revealed an increase of activated T cells in the tumor microenvironment after study therapy.
Conclusions: Compared with historic controls, re-irradiation plus pembrolizumab seemed to improve survival among bevacizumab-refractory patients but not among bevacizumab-naïve patients. CODEX revealed evidence of intratumoral infiltration of activated immune effector cells. A randomized, properly controlled trial of PD-1 blockade plus re-irradiation is warranted to further evaluate this regimen for bevacizumab-refractory patients, but alternative approaches are needed for bevacizumab-naïve patients.
Indexed on Europe PMC as PubMed record 39513953 (DOI 10.1158/1078-0432.ccr-24-1629). Its title names Pembrolizumab and its text names Glioma & glioblastoma; PubMed types it as a clinical trial report (Clinical Trial, Phase II). It was matched automatically to the idea "Neoadjuvant immunotherapy with surgical window for glioblastoma" and no figure has been checked by an editor.
One of the most cited trial reports Europe PMC returns for Pembrolizumab in Glioma & glioblastoma, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
- Matched by Pembrolizumab in the title and Glioma & glioblastoma in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.
- Chosen as a phase 2 or 3 report by the record's publication type or its own wording, not by reading the paper.