Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. Issue 4 (11th November 2020)

• Record Type: Journal Article
• Authors: Sahebjam, Solmaz; Forsyth, Peter A; Tran, Nam D; Arrington, John A; Macaulay, Robert; Etame, Arnold B; Walko, Christine M; Boyle, Theresa; Peguero, Edwin N; Jaglal, Michael; Mokhtari, Sepideh; Enderling, Heiko; Raghunand, Natarajan; Gatewood, Tyra; Long, Wendy; Dzierzeski, Jennifer L; Evernden, Brittany; Robinson, Timothy; Wicklund, Melissa C; Kim, Sungjune; Thompson, Zachary J; Chen, Dung-Tsa; Chinnaiyan, Prakash; Yu, Hsiang-Hsuan Michael
• Is Part Of: Neuro-oncology. Volume 23:Issue 4(2021)
• Page Start: 677
• Page End: 686
• Publication Date: 2020-11-11
• Subjects: bevacizumab -- hypofractionated stereotactic re-irradiation -- PD-L1 -- pembrolizumab -- recurrent high-grade glioma; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa260
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: 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.