title: Do BRAF inhibitors select for populations with different disease progression kinetics?
abstract: Ipilimumab, an anti-CTLA-4 monoclonal antibody, has been shown to improve overall survival in patients with metastatic melanoma. Preliminary data suggest that patients who fail BRAF inhibitor treatment experience a very rapid progression of disease. Such selectivity for more rapid disease progression may mean these patients do not receive the same benefit from subsequent treatment with ipilimumab as patients without prior BRAF inhibitor treatment. The current challenge is focused on how to identify and approach the two populations of fast and slow progressors and recent hypothesis suggest that treatment choice could be guided by baseline risk factors. However, no data have yet defined which the best sequence is and more research is needed to identify predictors of response in patients with metastatic melanoma to help guide whether a BRAF inhibitor or ipilimumab should be used first in sequential therapy.
authors.affiliation: Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Department of Melanoma, Istituto Nazionale Tumori Fondazione G. Pascale, Naples, Italy. paolo.ascierto@gmail.com
authors.forename: Paolo Antonio
authors.initials: PA
authors.lastname: Ascierto
authors.forename: Ester
authors.initials: E
authors.lastname: Simeone
authors.forename: Antonio Maria
authors.initials: AM
authors.lastname: Grimaldi
authors.forename: Marcello
authors.initials: M
authors.lastname: Curvietto
authors.forename: Assunta
authors.initials: A
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
authors.forename: Nicola
authors.initials: N
authors.lastname: Mozzillo
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf