Immune checkpoint inhibitors have shown significant antitumor activity in melanoma. However, previous randomized trials have excluded patients with untreated brain metastases due to concerns regarding central nervous system penetration and poor prognosis. In this phase II trial, 23 patients with stage IV melanoma and at least one 5-20 mm brain metastasis (untreated or radiographically progressing despite local therapy) were treated with pembrolizumab (a PD-1 inhibitor) every 2 weeks for up to 24 months to study the impact on brain metastasis radiographic response rate. Response to treatment was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Researchers found that 6 patients (26%) exhibited a brain metastasis response rate (95% CI 10% to 48%). Of note, 8 (35%) of patients could not be evaluated for brain metastasis response. The median progression-free and overall survival times were 2 months (95% CI 2 months to not reached) and 17 months (95% CI 10 months to not reached), respectively. At 24 months, 11 patients were alive (48%, 95% CI 31% to 73%). Interestingly, all patients who experienced disease progression had lower stromal PD-L1 expression and fewer CD8-positive tumor-infiltrating lymphocytes than those who responded to treatment. Neurologic adverse events occurred in 65% of patients, most of which were grade 1-2 in severity. Limitations of this study include the small sample size and the large number of unevaluable patients. Overall, results from this study suggest that pembrolizumab is active in small melanoma brain metastases and has an acceptable safety profile. However, larger studies are warranted to conclusively determine the antitumor effect of pembrolizumab in melanoma brain metastases.
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