Nivolumab + Ipilimumab First Doubles 5-Year OS vs Dabrafenib/Trametinib in BRAFV600-Mutant Melanoma

In the Phase III DREAMseq trial (NCT02224781), 267 untreated patients with BRAF V600-mutant metastatic melanoma were randomized to receive either nivolumab (a PD-1–directed monoclonal antibody) plus ipilimumab (a CTLA-4–directed monoclonal antibody) as first-line therapy (Arm A), followed by the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib upon progression, or the reverse sequence (Arm B). After a median follow-up of 58 months, 5-year OS was 63.3% with immunotherapy first, compared to 33.9% with targeted therapy first (p < 0.01, log-rank test). Five-year PFS similarly favored the immunotherapy-first sequence (39.4% vs. 12.8%). Confirmed ORRs were comparable (~51%), but response durability differed significantly—median DOR was not reached with initial nivolumab/ipilimumab, versus 15.5 months after initial dabrafenib/trametinib. Additionally, targeted therapy was associated with a higher rate of unconfirmed responses (41% vs. 17%) and earlier brain progression (median 8.4 vs. 12.2 months).