Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study |
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Authors: | Solmaz Sahebjam Peter A Forsyth Nam D Tran John A Arrington Robert Macaulay Arnold B Etame Christine M Walko Theresa Boyle Edwin N Peguero Michael Jaglal Sepideh Mokhtari Heiko Enderling Natarajan Raghunand Tyra Gatewood Wendy Long Jennifer L Dzierzeski Brittany Evernden Timothy Robinson Melissa C Wicklund Sungjune Kim Zachary J Thompson Dung-Tsa Chen Prakash Chinnaiyan Hsiang-Hsuan Michael Yu |
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Affiliation: | 1. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida;2. University of South Florida, Tampa, Florida;3. Beaumont Health and Oakland University School of Medicine, Royal Oak, Michigan, USA |
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Abstract: | BackgroundRadiotherapy 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).MethodsEligible 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.ResultsThirty-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%.ConclusionsThe 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. |
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Keywords: | bevacizumab hypofractionated stereotactic re-irradiation PD-L1 pembrolizumab recurrent high-grade glioma |
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