BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.
By: Jennifer Roux, Cecile Pages, Diane Malouf, Nicole Basset Seguin, Nika Madjlessi, Michel Baccard, Christelle Comte, Alain Archimbaud, Maxime Battistella, Manuelle Viguier, Samia Mourah, Martine Bagot, Céleste Lebbe

Departments of aDermatology bPathology cPharmacology, Hôpital Saint Louis, APHP dINSERM U976, Université Paris 7 Diderot, Paris, France.
2015-9-24; doi: 10.1097/CMR.0000000000000196
Abstract

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.





PMID:26397052






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