Abstract
Nivolumab plus ipilimumab provides clinical benefit in 57% of patients with melanoma with brain metastases.
Major finding: Nivolumab plus ipilimumab provides clinical benefit in 57% of patients with melanoma with brain metastases.
Approach: An open-label phase II trial assessed nivolumab plus ipilimumab in untreated brain metastases.
Impact: Combination therapy with nivolumab and ipilimumab achieves intracranial and extracranial responses.
Brain metastases occur frequently in patients with melanoma. The anti-CTLA4 antibody ipilimumab and the anti–PD-1 antibodies pembrolizumab and nivolumab have each achieved single-agent intracranial activity in clinical trials in patients with untreated brain metastases. Combination therapy with ipilimumab plus nivolumab has exhibited superior efficacy compared with either monotherapy in phase II and III trials of patients with advanced melanoma, but these trials have excluded patients with untreated brain metastases. To determine the safety and efficacy of nivolumab plus ipilimumab, Tawbi and colleagues conducted an open-label, phase II study, enrolling 94 patients with metastatic melanoma with at least one measurable, nonirradiated brain metastasis and no neurologic symptoms. The primary end points were the rates of intracranial clinical benefit, complete response, and partial response. Overall, 57% of patients experienced clinical benefit, with 26% of patients achieving a complete response and 30% achieving a partial response. In patients with an objective response in the brain, 90% were ongoing at the time of analysis. Extracranial clinical benefit was observed in 56% of patients. The safety profile was similar to what had been reported in patients with melanoma without brain metastases. Treatment-related grade 3–4 adverse events occurred in 55% of patients, with adverse events involving the central nervous system in 7% of patients. There was one treatment-related death, due to immune-related myocarditis. Taken together, the results of this phase II trial suggest that combination treatment with nivolumab and ipilimumab achieves intracranial responses in patients with melanoma with untreated brain metastases, without unexpected toxicity. These findings support further clinical investigation in patients with brain metastases.
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.
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