Pembrolizumab Plus Bevacizumab Shows Promise Among Previously Untreated Patients With Melanoma Brain Metastases

Results from a phase 2 study found that pembrolizumab plus bevacizumab demonstrated promising activity and safety among previously untreated patients with melanoma brain metastases. 

According to prior phase 1 results, “pembrolizumab was well tolerated, and although most neurologic toxicities were grade 1-2, the rate of RN [radiation necrosis] was 50% in patients with previous brain irradiation,” stated Sarah Weiss, MD, Rutgers Cancer Institute, New Brunswick, New Jersey, and coauthors. “The antiangiogenic and potential immune-enhancing properties of bevacizumab provided the basis for a phase II trial of pembrolizumab in combination with bevacizumab.” 

In this open-label study, researchers enrolled 37 patients who had not yet received anti–PD-1/L1 agents with ≥ 1 asymptomatic nonhemorrhagic metastatic melanoma brain metastases of 5 to 20 mm that did not require local therapy or steroids. Patients were assigned to receive 200 mg of pembrolizumab plus 7.5 mg/kg of bevacizumab once every 3 weeks for up to 4 cycles, followed by pembrolizumab monotherapy for up to 24 months or until disease progression or unacceptable toxicity. The primary end point was brain metastasis response rate. Key secondary end points included extracranial response rate, intracranial progression-free survival (PFS), overall survival (OS), and safety. 

At analysis, the brain metastasis response rate was 54.1%. The extracranial response rate was 56.3%, the median intracranial PFS was 2.2 years, and the median OS was 4.3 years. The 4-year OS rate was 51.6%. Grade 3 pembrolizumab-related adverse events occurred in 18.9% of patients and grade 3 bevacizumab-related adverse events occurred in 10.8% of patients. 

“Pembrolizumab/bevacizumab has clinical activity for melanoma patients with untreated [melanoma brain metastasis] with a [brain metastasis response rate] that exceeds historical data for anti–PD-1 monotherapy and appears less toxic than ipilimumab/nivolumab, although these regimens have not been compared in a randomized setting,” concluded Dr Weiss et al. 

“This prospective study provides data to support a comparative trial of combined PD-1/vascular endothelial growth factor inhibition versus PD-1/CTLA-4 inhibition for untreated [melanoma brain metastasis], and could later impact treatment of brain metastases from other diagnoses,” added Journal of Clinical Oncology associate editor Robert Maki, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York. 

Source: 

Weiss SA, Djuerinovic D, Wei W, et al. Phase II trial of pembrolizumab in combination with bevacizumab for untreated melanoma brain metastases. J Clin Oncol. Published online: March 6, 2025. doi: 10.1200/JCO-24-02219