In a phase II trial reported in Journal of Clinical Oncology, Weiss et al found that the combination of pembrolizumab and bevacizumab was active in patients with previously untreated melanoma brain metastases.
Study Details
In the trial, 37 patients, enrolled at Yale Cancer Center and Moffitt Cancer Center between August 2016 and February 2023, were treated with pembrolizumab at 200 mg every 3 weeks and bevacizumab at 7.5 mg/kg every 3 weeks for four cycles followed by pembrolizumab at 200 mg every 3 weeks for up to 24 months. Patients had received no prior PD-L1 inhibitor treatment and had ≥ 1 asymptomatic nonhemorrhagic 5–20-mm melanoma brain metastases that did not require immediate local therapy or steroids.
Key Findings
The brain metastasis objective response rate was 54.1% (95% confidence interval [CI] = 36.9%–70.5%). Higher pretreatment vessel density in the metastatic tumors and smaller on-therapy increases in circulating angiopoietin-2 were associated with objective response. The extracranial objective response rate was 56.3% (95% CI = 37.7%–73.6%).
Median intracranial progression-free survival was 2.2 years (95% CI = 0.41 years to not reached). Median overall survival was 4.3 years (95% CI = 1.6 years to not reached), with a 4-year overall survival rate of 51.6%.
Grade ≥ 3 pembrolizumab-related adverse events occurred in 18.9% of patients, most commonly increased alanine transaminase (11%) and increased aspartate transaminase (5%), and grade ≥ 3 bevacizumab-related adverse events occurred in 10.8%, most commonly hypertension (5%).
The investigators concluded: “Pembrolizumab with bevacizumab was well tolerated and demonstrated substantial activity in patients with untreated [melanoma brain metastasis] with promising [overall survival], justifying further evaluation of this regimen.”
Harriet M. Kluger, MD, of Yale University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.
Disclosures: The study was supported by Merck, Sharp and Dohme, LLC, and others.For full disclosures of all study authors, visit the ascopubs.org.
