title: BRAF inhibitor rechallenge in patients with advanced BRAF V600-mutant melanoma.
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.
authors.affiliation: Departments of aDermatology bPathology cPharmacology, Hôpital Saint Louis, APHP dINSERM U976, Université Paris 7 Diderot, Paris, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roux
authors.forename: Cecile
authors.initials: C
authors.lastname: Pages
authors.forename: Diane
authors.initials: D
authors.lastname: Malouf
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset Seguin
authors.forename: Nika
authors.initials: N
authors.lastname: Madjlessi
authors.forename: Michel
authors.initials: M
authors.lastname: Baccard
authors.forename: Christelle
authors.initials: C
authors.lastname: Comte
authors.forename: Alain
authors.initials: A
authors.lastname: Archimbaud
authors.forename: Maxime
authors.initials: M
authors.lastname: Battistella
authors.forename: Manuelle
authors.initials: M
authors.lastname: Viguier
authors.forename: Samia
authors.initials: S
authors.lastname: Mourah
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010091:Oximes / Q000008:administration & dosage*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics; D013449:Sulfonamides / Q000008:administration & dosage*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib