Optimal sequence of targeted therapy and immunotherapy for advanced BRAF-mutant melanoma

Combination nivolumab-ipilimumab as well as combination dabrafenib-trametinib have each shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma. The multicenter phase 3 DREAMseq trial was conducted to determine which initial treatment or treatment sequence produced the best efficacy. In step 1, patients were randomised to combination nivolumab-ipilimumab (arm A) or dabrafenib-trametinib (arm B), and as disease progression werd enrolled in step 2 to receive the alternate therapy. Overall survival (panel A, progression-free survival (panel B) and duration of response (panel C) were significantly superior in arm A compared with arm B. The study was stopped early by the independent Data Safety Monitoring Committee. The authors conclude that combination nivolumab-ipilimumab treatment, if necessary followed by dabrafenib-trametinib, should be the preferred treatment sequence for a large majority of BRAFV600-mutant metastatic melanoma patients.