Two-institution phase 2 trial of pembrolizumab plus bevacizumab for previously untreated melanoma brain metastases

Anti-VEGFR therapy enhances PD-1 inhibitor activity in preclinical models and has been used to treat perilesional cerebral edema and radiation necrosis. A two-institution phase 2 trial evaluated the combination of pembrolizumab and bevacizumab for previously untreated brain metastases from melanoma (MBM). Patients received four doses of pembrolizumab and bevacizumab every 3 weeks followed by up to 2 years of pembrolizumab. The brain metastasis response rate (primary endpoint) was 54.1% (95% CI 36.9-70.5) with extranial response rate 56.3% (37.7-73.6); median intracranial progression-free survival was 2,2 years (0.41-NR) and median overall survival was 4.3 years (1.6-NR). Grade 3 treatment-related adverse event rates from bevacizumab and pembrolizumab were 10.8% and 18.9%, respectively. The authors conclude that the combination of pembrolizumab and bevacizumab was well tolerated and demonstrated substantial activity among patients with previously untreated MBM.