ASCO 2025 | Final DREAMseq results favor first-line immunotherapy for melanoma

At the time the DREAMSeq trial was launched in 2015, there were two combination therapy approaches for patients with metastatic treatment-naive, BRAF mutant melanoma. One was targeted therapy looking at BRAF MEK inhibitors, and the other was combination immunotherapy, looking at anti-PD-1, anti-CTLA-4 combination. And both produced overall survival advantage versus standard of care. And the question at the time of the DREAMSeq trial was launched was which approach was preferred, and because both were FDA approved, was there a preferred sequence. And so the DREAMSeq trial took patients with treatment-naive BRAF mutant melanoma, stratified them by performance status and LDH, and randomized them in step one to combination nivo-ipi immune therapy versus dabrafenib-trametinib targeted therapy. And if patients showed progression and met the eligibility criteria, they crossed over to step two, which was the alternative therapy. Because we thought the survival curves might cross, we chose two-year overall survival as the primary endpoint, estimating that the immunotherapy first would have 72% of patients alive at two years versus 52% for the targeted therapy first. We first presented the clinical data at the inaugural ASCO plenary session online in 2021 when the study was stopped early because of a clinically meaningful two-year overall survival benefit favoring immunotherapy first with a 20% difference in two-year overall survival. Exactly replicating what we had predicted from the start of the study. And when we looked at things at that time, it looked like most of a group of patients benefited from immunotherapy first in terms of two-year overall survival, and that there was primarily an improved duration of response related to the immunotherapy first. About 10% of patients who got immunotherapy first actually did worse and died earlier than with targeted therapy. And all of those patients had aggressive disease and didn’t receive targeted therapy in crossover, at least on protocol. And the toxicities were similar between the two arms in terms of incidence, but differed according to the known toxicities of the classes of therapy. So, what we’ll be presenting at ASCO this year is the five-year data, which is the endpoint of the clinical trial with now median overall survival from time of, or median time from randomization being close to five years.

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