Treatment sequence can impact survival in patients with BRAF V600-mutant metastatic melanoma, according to results from the phase 3 DREAMseq trial.
Starting treatment with nivolumab plus ipilimumab (nivo-ipi) and proceeding to dabrafenib plus trametinib (dab-tram) led to superior overall survival (OS) when compared with the opposite treatment sequence.
These results were presented at the inaugural American Society of Clinical Oncology (ASCO) Virtual Plenary Series by Michael B. Atkins, MD, of the Georgetown Lombardi Comprehensive Cancer Center in Washington, DC.
The DREAMseq trial (ClinicalTrials.gov Identifier: NCT02224781) included 265 patients with treatment-naive BRAF V600-mutant metastatic melanoma. The patients’ median age was 61 years (range, 25-85 years).
Patients were randomly assigned to arm A or arm B for initial treatment. Arm A received nivo-ipi induction for 12 weeks followed by nivolumab maintenance for 72 weeks (133 patients). Arm B received continuous dab-tram (132 patients). Baseline characteristics were well balanced between the 2 arms.
Patients who experienced disease progression on initial treatment went on to receive the alternate therapy. Patients in arm C received continuous dab-tram, and patients in arm D received nivo-ipi followed by nivolumab maintenance. At a median follow-up of 27.7 months, 27 patients had gone on to arm C and 46 to arm D.
Results: Efficacy and Safety
The overall response rates were 46% in arm A, 43% in arm B, 48% in arm C, and 30% in arm D.
The median duration of response was not reached in arm A and was 12.7 months in arm B (P <.001). At the data cutoff, 88% of responders in arm A were still in response, compared with 49% of responders in arm B.
The median progression-free survival (PFS) was 11.8 months in arm A and 8.5 months in arm B. The 2-year PFS rate was 42% and 19%, respectively (P =.054).
The 2-year overall survival rate was 72% for patients who started treatment with nivo-ipi (arms A and C) and 52% for those who started with dab-tram (arms B and D; P =.0095).
A total of 100 deaths were reported, with 38 occurring in patients who started on nivo-ipi and 62 in those who started on dab-tram.
Grade 3 or higher adverse events (AEs) were observed in 60% of patients in arm A, 52% in arm B, 54% in arm C, and 50% in arm D.
Fatal treatment-related AEs occurred in in 2 patients in arm A (myocarditis and gastrointestinal toxicity) and 1 in arm C (stroke).
“We conclude that, in this population with an oncogene-driven tumor and an effective targeted therapy, nivo-ipi followed by BRAF/MEK inhibitors, if necessary, should be the preferred treatment sequence,” Dr Atkins concluded.
Disclosures: This research was supported by Bristol Myers Squibb. Dr Atkins disclosed affiliations with Bristol Myers Squibb and several other companies. Please see the original reference for a full list of disclosures.
Atkins MB, Lee SJ, Chmielowski B, et al. DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134. ASCO Virtual Plenary; November 16, 2021. Abstract 356154.