Combination treatment with a BRAF inhibitor and
MEK inhibitor is the standard of care for patients with advanced BRAFV600 mutation-positive
melanoma. With the currently available combinations of
dabrafenib plus
trametinib and
vemurafenib plus
cobimetinib, median progression-free survival (PFS) of over 12 months has been achieved. However, treatment resistance and disease recurrence remain a clinical challenge. Areas covered:
Encorafenib in combination with bimetinib offers a new approach that may offer benefits over existing BRAF/
MEK inhibitor combinations. Expert opinion: While other BRAF/
MEK inhibitor combinations have achieved a median overall survival (OS) of 22 months, patients with advanced BRAF mutation-positive
melanoma treated with
encorafenib plus
binimetinib achieved a median OS of 33.6 months in the phase III COLUMBUS trial. PFS also appears to be improved with
encorafenib plus
binimetinib. This improved efficacy may be related to the distinct pharmacokinetics of
encorafenib, with prolonged binding to the target molecule providing greater BRAF inhibition and increased potency compared with other drugs in the same class. Increased specificity of
encorafenib may also result in better tolerability with less off-target effects, including reduced occurrence of
pyrexia and photosensitivity.
Encorafenib plus
binimetinib seems likely to emerge as a valuable therapeutic alternative to established BRAF/
MEK inhibitor combinations.