A PHASE II trial evaluating the combination of pembrolizumab and bevacizumab in patients with untreated melanoma brain metastases (MBM) has demonstrated substantial clinical activity and promising survival outcomes. The study enrolled 37 patients who were anti–PD-(L)-1–naïve and had at least one asymptomatic, nonhemorrhagic MBM between 5-20 mm, not requiring immediate local therapy or steroids.
Patients received four doses of bevacizumab and pembrolizumab every three weeks, followed by up to two years of pembrolizumab monotherapy. The brain metastasis response rate was 54.1% (95% CI, 36.9 to 70.5), while the extracranial response rate reached 56.3% (95% CI, 37.7 to 73.6). Median intracranial progression-free survival was 2.2 years (95% CI, 0.41 to not reached), and median overall survival (OS) was 4.3 years (95% CI, 1.6 to not reached). At four years, 51.6% of patients remained alive.
The regimen was well tolerated, with grade 3 treatment-related adverse events occurring in 10.8% of patients due to bevacizumab and 18.9% due to pembrolizumab. The study also found that patients with higher pretreatment vessel density in metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were more likely to respond to treatment.
These findings highlight the potential of combining pembrolizumab with bevacizumab for patients with untreated MBM, supporting further investigation of this approach.
Reference: Weiss SA et al. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. JCO. 2025. doi:10.1200/JCO-24-02219.
Anaya Malik | AMJ
