Impact of sequence of checkpoint inhibitors and BRAF/MEK inhibitors on development of brain metastases in BRAFV600-mutant melanoma

The multinational SECOMBIT trial included patients with metastatic unresectable BRAFV600-mutant melanoma, who were treated with the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A), or ipilimumab and nivolumab until progressive disease followed by encorafenib and binimetinib (arm B), or encorafenib plus binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib and binimetinib (arm C). The median follow-up was 56 months. Development of brain metastases was seen in 23 of 69 patients in arm A, 11 of 69 patients in arm B, and 9 of 68 patiens in arm C. The 60-month brain metastasis-free survival rates were 56% for arm A, 80% for arm B (versus A HR 0.40; 95% CI 0.23-0.58), and 85% for arm C (0.35; 0.16-0.76). The authors conclude that the sequence of checkpoint inhibitors and BRAF/MEK inhibitors was associated with brain metastasis-free survival among patients with metastatic unresectable BRAFV600-mutant melanoma.