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Updated: Sep 30, 2025
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas
Priscilla K Brastianos1, Albert E Kim2, Anita Giobbie-Hurder3
1Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA. pbrastianos@mgh.harvard.edu.
Abstract:
High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31-0.66) and a median PFS of 7.6 months (90% CI: 3.4-12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.
Insights
Pembrolizumab shows promise for recurrent high-grade meningiomas, with 48% of patients alive and progression-free at 6 months. This PD-1 inhibitor offers a potential new treatment avenue for these aggressive brain tumors.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer research
Background:
- High-grade meningiomas present significant neuro-cognitive challenges and limited therapeutic options.
- The immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression are implicated in meningioma aggressiveness.
Purpose of the Study:
- To evaluate the efficacy of pembrolizumab, a PD-1 inhibitor, in patients with recurrent and progressive high-grade meningiomas.
- To assess the primary endpoint of progression-free survival at 6 months (PFS-6) and secondary endpoints including survival and toxicity.
Main Methods:
- A single-arm, open-label, phase 2 clinical trial (NCT03279692) was conducted.
- Twenty-five evaluable patients with recurrent/progressive grade 2 and 3 meningiomas received pembrolizumab.
- Key assessments included PFS-6, progression-free survival (PFS), overall survival, intracranial response, and adverse events.
Main Results:
- The study met its primary endpoint, achieving a PFS-6 rate of 0.48 (90% exact CI: 0.31-0.66).
- Median PFS was 7.6 months (90% CI: 3.4-12.9 months).
- Grade 3 or higher treatment-related adverse events occurred in 20% of patients.
Conclusions:
- Pembrolizumab demonstrates promising efficacy in a subset of patients with recurrent high-grade meningiomas.
- Further research is warranted to elucidate the specific TME factors driving response to immunotherapy in meningiomas.
