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- W2014696095 abstract "Targeted therapy for BRAF-mutant melanoma has revolutionised the management of patients with metastatic melanoma 1 Chapman PB Hauschild A Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011; 364: 2507-2516 Crossref PubMed Scopus (6025) Google Scholar , 2 Hauschild A Grob JJ Demidov LV et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012; 380: 358-365 Summary Full Text Full Text PDF PubMed Scopus (2313) Google Scholar and ignited a quest for even more effective strategies. Situated just downstream of BRAF is MEK, which has become a second molecular target of great interest. The MEK inhibitor trametinib was recently approved by the US Food and Drug Administration (FDA), and other MEK inhibitors are in clinical development. 3 Ascierto PA Schadendorf DA Berking C et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013; 14: 249-256 Summary Full Text Full Text PDF PubMed Scopus (508) Google Scholar , 4 Flaherty KT Robert C Hersey P et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012; 367: 107-114 Crossref PubMed Scopus (1681) Google Scholar Targeted drugs have pushed cytotoxic chemotherapy research into the background, yet chemotherapy regimens are still offered as first-line therapy in countries where access to targeted drugs is limited. Chemotherapy has a deservedly poor reputation in the treatment of advanced melanoma, but it is now valid to ask whether targeted therapy has made chemotherapy obsolete, or alternatively whether combination with a molecularly targeted agent could breathe new life into old drugs. Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised studySelumetinib plus dacarbazine showed clinical activity in patients with BRAF-mutant cutaneous or unknown primary melanoma, reflected by a significant benefit in progression-free survival compared with placebo plus dacarbazine group, although no significant change in overall survival was noted. The tolerability of this combination was generally consistent with monotherapy safety profiles. Full-Text PDF" @default.
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- W2014696095 title "Has targeted therapy for melanoma made chemotherapy obsolete?" @default.
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- W2014696095 doi "https://doi.org/10.1016/s1470-2045(13)70298-5" @default.
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