Best of ASCO 2025 narrative review article Ó? Skin cancer

DREAMseq: A phase III trial of treatment sequences in BRAFV600-mutant (m) metastatic melanoma (MM) -Final clinical resultsBRAF is one of the most commonly mutated oncogenes in melanoma 1 .Patients with BRAF-mutant MM can be treated either with targeted therapy (TT) or with combined immunotherapy (IO) 2-4 such as nivolumab and ipilimumab 5 both of which have demonstrated significant clinical benefit.However, the optimal sequencing of these treatments has remained unclear, with limited data available to guide clinical decision-making.The DREAMseq, led by ECOG-ACRIN Cancer Research Group, was a phase 3, two-arm, two-step, open-label, randomized study.The trial enrolled treatment-naive patients with BRAFV600-mutant MM, who were stratified by ECOG performance status (PS) and lactate dehydrogenase (LDH) levels, and then randomized to arm A (combination nivolumab/ipilimumab) or arm B (dabrafenib/trametinib) in Step 1, and at disease progression, if eligible, they were enrolled in Step 2 receiving the alternate therapy, dabrafenib/trametinib (Arm C) or nivolumab/ipilimumab (Arm D).The primary endpoint was 2-year overall survival (OS), with secondary endpoints including 3-year OS, overall response rate (ORR), response duration, progression-free survival (PFS), crossover feasibility, and safety.The primary analysis-first presented at the 2023 ASCO inaugural virtual plenary session and published in JCO 6 -demonstrated a significantly higher 2-year OS for patients receiving IO first (72% vs. 52%; p = 0.01).