Sequencing Debate for Frontline BRAF-Mutant Melanoma in Full Force

Source: OncLive, October 2020

Now that BRAF/MEK combination regimens and immunotherapeutic approaches have demonstrated significant benefit in patients with BRAF-mutated melanoma, efforts are being focused on addressing the question of sequencing and determining biomarkers for optimal patient selection, according to Geoffrey T. Gibney, MD.

Research such as the COMBI-d and COMBI-v trials have demonstrated that durable responses can be achieved with BRAF/MEK combinations, and many patients who receive these regimens have proven to be long-term survivors, according to Gibney. Pooled data from the 2 trials indicated that patients who received the combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) experienced a 5-year PFS rate of 19% and a 5-year overall survival (OS) rate of 34%.

Now, efforts like the EA6134 trial (NCT02224781) are examining whether it is more beneficial to utilize a BRAF/MEK combination or an immunotherapy combination first in a patient who presents with BRAF V600-mutated disease. Specifically, the phase 3 trial will examine initial treatment with ipilimumab (Yervoy) and nivolumab (Opdivo) followed by dabrafenib and trametinib versus initial treatment with dabrafenib/trametinib followed by ipilimumab/nivolumab in patients with unresectable disease.