Top Line: Does combination nivolumab and ipilimumab provide long-term intracranial control for melanoma patients with brain metastases?
The Study: Back in ‘18, the phase 2 CheckMate 204 trial demonstrated that patients with asymptomatic brain metastases from melanoma derive an intracranial benefit similar to their extracranial benefit from combined nivolumab and ipilimumab. Here is long-term followup of CheckMate 204 that also includes outcomes for a smaller cohort of patients (15%) with symptomatic disease. 119 patients were treated with combo nivo+ipi and had brain MRI every 6 weeks. Over half of asymptomatic patients (53.5% on independent review) had clinical benefit, which included 33% with investigator assessed complete response, 21% with partial response, and 4% with at least 6 months stable disease. Median duration of response wasn’t reached with 58% of responding patients maintaining response at 2 years. Response wasn’t reported according to PD-L1 status. Median intracranial PFS was 39.3 months, and overall survival at 3 years was a whopping 72%. In fact, disease and survival outcomes were comparable to those of metastatic melanoma patients without brain mets. It was a different story, though, for those with symptomatic disease with a 21% clinical benefit rate including 6% complete response and 17% partial response with 61% having progressive intracranial disease. Median intracranial PFS was just 1.2 months and 3-year overall survival was 37%. These long-term results provide data to carefully select patients who may do well with initial immunotherapy alone for asymptomatic mets.
TBL: Over half of patients with limited, asymptomatic melanoma brain metastases respond to combination nivo + ipi with a 3-year intracranial PFS rate of 54% and OS rate of 72%. However, those with symptomatic disease have low response rates and relatively rapid intracranial progression. | Tawbi, Lancet Oncol 2021