J Clin Oncol: Optimal treatment sequence for patients with BRAF V600 mutant metastatic melanoma

In patients with BRAF V600 mutant metastatic melanoma, the combination of programmed cell death protein 1/cytotoxic T lymphocyte-4 blocker and dual BRAF/MEK inhibitors has demonstrated significant clinical benefit and received broad regulatory approval
.
However, in this patient population, there is little prospective data to guide the choice
of initial treatment or treatment sequence.

The study aimed to determine which initial treatment or sequence of treatment would yield the best results
.

This is a phase 3 trial that enrolled patients with untreated BRAFV600-mutated metastatic melanoma randomly divided into two groups, with nivolumab/ipilimab (group A) or dabrafenib/trametinib (group B) in the first step, and then progression to step 2, with a change of treatment, dabrafenib/trametinib (group C) or nivolumab/ipilimab (group D).

The primary endpoint was 2-year overall survival (OS).

Secondary endpoints were 3-year OS, objective response rate, duration of response, progression-free survival, crossover feasibility, and safety
.

Overall survival and progression-free survival in both groups

A total of 265 patients were enrolled, of which 73 entered the second (27 in group C and 46 in group D).

Due to the achievement of significant clinical endpoints, an independent data safety monitoring committee stopped the study
early.
The 2-year OS was 71.
8% (95% CI 62.
5-79.
1) in group A and 51.
5% (95% CI 41.
7-60.
4, p=0.
010)
in group B.
Progression-free survival in step 1 favored group A (P=0.
054).

objective response rate, group A: 46.
0%; Group B: 43.
0%; Group C: 47.
8%; Group D: 29.
6%.

The median duration of response was not achieved in group A and 12.
7 months (p<0.
001)
in group B.
Among patients with documented disease progression, cross-treatment was 52% of
patients.
The incidence of ≥grade 3 toxicity was similar in both groups, and the toxicity distribution was consistent
with expectations.

In summary, if necessary, nivolumab/ipilimab in combination with BRAF and MEK inhibitors should be the preferred treatment order
for the vast majority of patients with BRAF V600 mutant metastatic melanoma.

Original source:

Michael B.
Atkins, et al.
Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma: The DREAMseq Trial—ECOG-ACRIN EA6134.
Journal of Clinical Oncology.
October 26, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
01763