CheckMate 204: Long-Term Outcomes With Nivolumab Plus Ipilimumab in Active Melanoma Brain Metastases

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As reported in The Lancet Oncology by Tawbi et al, final results of the phase II CheckMate 204 trial indicate good long-term outcomes with the combination of nivolumab and ipilimumab in patients with asymptomatic active melanoma brain metastases, with poorer outcomes observed in those with symptomatic metastases.

Study Details

In the multicenter trial, 119 patients with measurable melanoma brain metastases (0.5–3.0 cm in diameter) enrolled between February 2015 and November 2017 received nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg every 3 weeks for four doses followed by nivolumab at 3 mg/kg every 2 weeks for up to 2 years or until disease progression or unacceptable toxicity.

Among the 119 patients, 111 in the asymptomatic cohort had no neurologic symptoms or baseline corticosteroid use and 18 in the symptomatic cohort had stable neurologic symptoms and could be receiving low-dose dexamethasone. The primary endpoint was investigator-assessed intracranial clinical benefit rate (complete response, partial response, or stable disease ≥ 6 months) assessed in all treated patients.

Key Findings

Median follow-up was 34.3 months (interquartile range [IQR] = 14.7–36.4 months) in the asymptomatic cohort and 7.5 months (IQR = 1.2–35.2 months) in the symptomatic cohort.

In the asymptomatic cohort, clinical benefit was observed in 58 patients (57.4%, 95% confidence interval [CI] = 47.2%–67.2%), objective response was seen in 54 (53.5%, 95% CI = 43.3%–63.5), and complete response was observed in 33 (32.6%). On blinded independent central review assessment of 50 patients with response, median duration of response was not reached, with response lasting more than 2 years in 58%.

In the symptomatic cohort, clinical benefit was observed in three patients (16.7%, 95% CI = 3.6%–41.4%), objective response was noted in three (16.7%, 95% CI = 3.6%–41.4%), and complete response was observed in three (16.7%). On blinded independent central review assessment of three patients who had achieved a response, the median duration of response was not reached, with all responses ongoing at more than 2.5 years.

In the asymptomatic cohort, 36-month intracranial progression-free survival was 54.1% (95% CI = 42.7%–64.1%), and overall survival was 71.9% (95% CI = 61.8%–79.8%). In the symptomatic cohort, 36-month intracranial progression-free survival was 18.9% (95% CI = 4.6%–40.5%), and overall survival was 36.6% (95% CI = 14.0%–59.8%).

Subsequent systemic therapy was received by 19% of the asymptomatic cohort and 22% of the symptomatic cohort. More than 90% of patients had stopped treatment at the last database lock in 2018; few changes in treatment-related adverse events were observed since the prior report of the study.

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

Hussein A Tawbi, MD, of the Department of Melanoma Medical Oncology at The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet Oncology article.

Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of the study authors, visit

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