Abstract
Treatment with nivolumab alone or nivolumab plus ipilimumab achieves intracranial responses.
Major finding: Treatment with nivolumab alone or nivolumab plus ipilimumab achieves intracranial responses.
Concept: Nivolumab with or without ipilimumab exhibits no unexpected toxicities in patients with brain metastases.
Impact: Nivolumab plus ipilimumab may be effective first-line therapy in patients with untreated brain metastases.
Immune checkpoint blockade with nivolumab monotherapy or combination nivolumab plus ipilimumab has improved survival in patients with melanoma. However, it is not known if these therapies are effective in active brain metastases. Long and colleagues evaluated the safety and efficacy of nivolumab alone or in combination with ipilimumab in an open-label phase II trial that treated 77 patients with melanoma brain metastases in three cohorts. In cohort A, 35 patients with asymptomatic brain metastases without previous local brain therapy were treated with nivolumab plus ipilimumab. In cohort B, 26 patients with asymptomatic brain metastases without previous local brain therapy were treated with nivolumab alone. In cohort C, 16 patients with active brain metastases or who had failed local therapy were treated with nivolumab monotherapy. The primary endpoint was intracranial response from week 12, and secondary endpoints included safety. Intracranial responses were achieved by 16 of 35 (46%) patients in cohort A, including 6 intracranial complete responses, 5 of 25 (20%) patients in cohort B, including 3 intracranial complete responses, and 1 of 16 (6%) patients in cohort C. Patients who had progressed on combined BRAF and MEK inhibitors had poorer progression-free survival, supporting first-line up-front treatment with ipilimumab plus nivolumab. No unexpected toxicities occurred. Treatment-related grade 3–4 adverse events occurred in 54% of patients in cohort A, 16% of patients in cohort B, and 13% of patients in cohort C. Taken together, the results of this phase II trial suggest that immune checkpoint blockade with nivolumab or nivolumab plus ipilimumab is effective in melanoma brain metastases. As a high proportion of patients achieved responses with combination therapy, more than that observed with nivolumab monotherapy, these findings support the use of nivolumab plus ipilimumab as first-line therapy in patients with asymptomatic untreated 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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