Assuntos
Produtos Biológicos/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Couro Cabeludo/efeitos dos fármacos , Neoplasias Cutâneas/tratamento farmacológico , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/secundário , Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Herpesvirus Humano 1 , Humanos , Injeções Intralesionais , Transplante de Fígado/efeitos adversos , Masculino , Terapia Viral Oncolítica/métodos , Couro Cabeludo/patologia , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
No head-to-head studies exist comparing BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) combination treatments for BRAF-mutant melanoma. A side-by-side analysis of randomized phase III trials is presented that evaluated dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib. The baseline characteristics, efficacy, and safety were compared: COMBI-v (dabrafenib/trametinib versus vemurafenib); coBRIM (vemurafenib/cobimetinib versus vemurafenib); and COLUMBUS (encorafenib/binimetinib versus encorafenib and vemurafenib). Vemurafenib was the control arm in all studies. The data sources included literature databases, European public assessment reports, U.S. Food and Drug Administration review documents, and prescribing information. The baseline characteristics were similar, except for coBRIM, which had a higher proportion of patients with elevated lactate dehydrogenase (LDH) levels. The median progression-free survival (PFS) and overall response rate (ORR) were similar across the trials, although numerically higher values were observed with encorafenib/binimetinib. In contrast, the median overall survival (OS) was numerically longer with encorafenib/binimetinib (33.6 months) compared to dabrafenib/trametinib (25.6 months) and vemurafenib/cobimetinib (22.3 months). Among vemurafenib arms, PFS, ORR, and OS were similar, despite variations in the baseline LDH. Each combination displayed a unique safety profile, with higher incidences of pyrexia with dabrafenib/trametinib and photosensitivity reactions with vemurafenib/cobimetinib. This analysis of BRAFi/MEKi combinations for BRAF-mutant melanoma, while limited as not a direct head-to-head clinical trial, highlights the differences in tolerability and efficacy that may be useful for therapeutic decision making.