Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.
Other Scholarly Work
Sahebjam, Solmaz, Forsyth, Peter A, Tran, Nam D et al. (2021). Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.
. NEURO-ONCOLOGY, 23(4), 677-686. 10.1093/neuonc/noaa260
Sahebjam, Solmaz, Forsyth, Peter A, Tran, Nam D et al. (2021). Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.
. NEURO-ONCOLOGY, 23(4), 677-686. 10.1093/neuonc/noaa260
Radiotherapy may synergize with programmed cell death 1 (PD1)/PD1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high-grade gliomas (HGGs).
Methods
Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W.
Results
Thirty-two patients were enrolled (bevacizumab-naïve, n = 24; bevacizumab-resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab-naïve cohort, 20 patients (83%) had a complete response or partial response. The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab-resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (n = 20/26; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%.
Conclusions
The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.
