Available treatments for patients with melanoma with BRAF mutations include the cancer immunotherapy nivolumab/ ipilimumab combination and the dabrafenib/trametinib combination, which also targets BRAF mutations. The results of the DREAMseq phase 3 trial, which tested which of the two treatments is more effective used first, reported that nivolumab/ipilimumab as first-line treatment and dabrafenib/trametinib as second-line treatment at disease progression was superior to the reverse order of first-line treatment with dabrafenib/trametinib and second-line treatment with nivolumab/ipilimumab.

The open-label, multicenter trial began in June 2015 and enrolled a total of 265 patients through June 2021. Enrolled patients were randomized to two treatment arms, with 133 patients starting treatment with nivolumab/ipilimumab as first-line (nivolumab/ipilimumab arm) and 132 patients starting treatment with dabrafenib/trametinib as first-line (dabrafenib/trametinib arm). Twenty-seven patients in the nivolumab/ipilimumab arm subsequently failed and switched to dabrafenib/trametinib as second-line treatment, and 46 patients in the dabrafenib/trametinib arm switched to nivolumab/ipilimumab.

The 2-year survival rates for both treatment arms were 71.8% in the nivolumab/ipilimumab arm and 51.5% in the dabrafenib/trametinib arm, respectively. Median progression-free survival was 11.8 months in the nivolumab/ipilimumab arm and 8.5 months in the dabrafenib/trametinib arm, demonstrating better outcomes for patients who started first-line nivolumab/ipilimumab.

The median progression-free survival for patients who crossed over from nivolumab/ipilimumab to dabrafenib/trametinib was 9.9 months, while the median progression-free survival for patients who crossed over from dabrafenib/trametinib to nivolumab/ipilimumab was shorter, at 2.9 months.

In first-line treatment, objective response rates were similar at 46% for nivolumab/ipilimumab and 43% for dabrafenib/trametinib, whereas in second-line treatment, objective response rates were 47.8% for dabrafenib/trametinib crossover and 29.6% for nivolumab/ipilimumab crossover.

Grade 3 or higher serious adverse events were similar in 59.5% of patients who received nivolumab/ipilimumab as first-line treatment and 53.1% of patients who received dabrafenib/trametinib as first-line treatment, and were also similar in 53.8% and 50.0% of patients who received dabrafenib/trametinib as second-line treatment and nivolumab/ipilimumab, respectively.

The researchers concluded that the use of a BRAF/MEK inhibitor should be favored after nivolumab/ ipilimumab in patients with BRAF-mutated melanoma.