BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma

In around 50% of melanomas, the BRAF V600 mutation, resulting in an activation of the MAP kinase pathway, is detected. BRAF inhibitors have shown remarkable activity on the disease. However, efficacy is short-lived in most cases, with a median disease-free survival of 6 months. This short duration of response could be explained by the acquisition of resistance mechanisms. Some cancers show sensitivity to the reintroduction of previously active drugs after disease progression. We carried out a retrospective monocentric study on patients with BRAF V600-mutated melanoma who were rechallenged with BRAF inhibitors that were previously beneficial, but in whom the disease had progressed. Nine patients were included. Five patients showed a subsequent partial response, two showed a dissociated response leading to clinical improvement, and two showed no radiological nor clinical response. Eight patients who received rechallenge BRAF inhibitor had received an intercurrent treatment with ipilimumab. These cases suggest that intermittent treatment with BRAF inhibitors could provide clinical benefit and that sequential therapies should be further evaluated in clinical trials.