Optimal regimen of short-term MAPK pathway inhibition for pembrolizumab-treated advanced BRAFV600-mutated melanoma

Continuous combination of MAPK pathway inhibition (MAPKi) and anti-PD-(L)1 showed high response rates, but only limited improvement in progression-free survival at the cost of a high frequency of treatment-related adverse events in patients with BRAF^V600-mutated melanoma. Short –term MAPKi induced T-cell infiltration in patients and was synergistic with anti-PD-1 in a melanoma mouse model. The phase 2 IMPemBra trial in The Netherlands found that the combination of pembrolizumab plus intermittent dabrafrenib and trametinib was more feasible and tolerable than continuous triple therapy. The efficacy was promising and more favorable than pembrolizumab monotherapy.