Pembrolizumab is well tolerated and achieves durable intracranial responses lasting more than 24 months.

  • Major finding: Pembrolizumab is well tolerated and achieves durable intracranial responses lasting more than 24 months.

  • Approach: A phase II trial evaluated the safety and efficacy of pembrolizumab in 23 patients with brain metastases.

  • Impact: Pembrolizumab may be beneficial for the treatment of patients with melanoma with brain metastases.

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Immune checkpoint blockade with the anti–PD-1 antibody pembrolizumab has achieved responses in a variety of tumor types including melanoma. However, the randomized trials of pembrolizumab in patients with melanoma have excluded patients with untreated brain metastases. In a phase II trial, Kluger and colleagues investigated the safety and activity of pembrolizumab in a cohort of 23 patients with melanoma with one or more asymptomatic brain metastases. The primary endpoint was brain metastasis response. Overall, 6 patients (26%) had a brain metastasis response, including 4 complete and two partial responses. One patient had stable disease and 8 patients had progressive disease. Intracranial responses were concordant with systemic responses. Eight of the patients (35%) were unevaluable for a brain metastasis response, but 3 of these patients remained progression free after more than 30 months, suggesting that the clinical benefit rate may be higher than the overall response rate indicates. The median progression-free survival was 2 months, and the median overall survival was 17 months. Pembrolizumab was well tolerated, with the majority of adverse events being grade 1–2. Neurologic adverse events occurred in 65% of patients, all but one grade 1–2. Responses were associated with high expression of PD-1 and pretreatment tumor CD8 T-cell density. Taken together, these findings demonstrate that immune checkpoint blockade with pembrolizumab is safe and can achieve durable responses in melanoma brain metastases. This long-term follow-up study supports further investigation and clinical use of pembrolizumab in patients with cancer with small, asymptomatic brain lesions.

Kluger HM, Chiang V, Mahajan A, Zito CR, Sznol M, Tran T, et al. Long-term survival of patients with melanoma with active brain metastases treated with pembrolizumab on a phase II trial. J Clin Oncol 2018 Nov 8 [Epub ahead of print].

Note: Research Watch is written by Cancer Discovery editorial staff. Readers are encouraged to consult the original articles for full details. For more Research Watch, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/CDNews.

©2019 American Association for Cancer Research.
2019
American Association for Cancer Research.