Final results from the CheckMate 204 trial show a lasting benefit with combination nivolumab and ipilimumab in patients with asymptomatic melanoma brain metastases (MBM).

However, the combination was less effective in patients with symptomatic MBM. Researchers reported these results in The Lancet Oncology.

The phase 2 CheckMate 204 trial (ClinicalTrials.gov Identifier: NCT02320058) included 119 patients with measurable MBM (0.5-3.0 cm in diameter) who were treated at 28 sites in the United States.


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The patients received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) intravenously every 3 weeks for 4 doses, followed by nivolumab (3 mg/kg) every 2 weeks for up to 2 years, until disease progression or unacceptable toxicity.

There were 101 asymptomatic patients. The remaining 18 patients were symptomatic, which meant they either had neurological signs or symptoms at baseline or were receiving dexamethasone.

Results

The median follow-up was 34.3 months for the asymptomatic cohort and 7.5 months for the symptomatic cohort.

In the asymptomatic cohort, 57.4% of patients had investigator-assessed intracranial clinical benefit, and 53.5% had an objective intracranial response. The median duration of response was not reached.

In the symptomatic cohort, 16.7% of patients had investigator-assessed intracranial clinical benefit, and 16.7% had an objective response. The median duration of response was not reached.

In the asymptomatic cohort, at 36 months, the intracranial progression-free survival (PFS) rate was 54.1%, and the overall survival (OS) rate was 71.9%. In the symptomatic cohort, the intracranial PFS rate was 18.9% and the OS rate was 36.6% at 36 months.

The rate of grade 3-4 treatment-related adverse events was 55% in the asymptomatic cohort and 67% in the symptomatic cohort. There was 1 treatment-related death in the asymptomatic cohort. The cause of death was myocarditis.

“The durable 3-year response, overall survival, and progression-free survival rates for asymptomatic patients support first-line use of nivolumab plus ipilimumab,” the researchers concluded. “Symptomatic disease in patients with MBM remains difficult to treat, but some patients achieve a long-term response with the combination.”

Disclosures: This research was supported by Bristol Myers Squibb. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Tawbi HA, Forsyth PA, Hodi FS, et al. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): Final results of an open-label, multicentre, phase 2 study. Lancet Oncol. Published online November 10, 2021. doi:10.1016/S1470-2045(21)00545-3