Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings.

Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings.

Publication date: Apr 12, 2019

Selective inhibition of the MAPK pathway with BRAF and MEK inhibitors has emerged as a key component of the treatment of BRAF-mutant unresectable/locally advanced metastatic melanoma. Areas covered: Current data are presented on the efficacy and safety of BRAFi + MEKi combination therapy (dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib) from phase I, II, and III trials in the unresectable/locally advanced metastatic setting, as well as neoadjuvant and adjuvant applications. The theoretical basis, pre-clinical findings, clinical trial results and current ongoing clinical studies of combined BRAF/MEK inhibition with immunotherapy, also known as “triplet therapy,” are also explored. Expert opinion: Combination therapy with BRAF and MEK inhibitors dramatically improves response rates, progression free survival and overall survival in patients with BRAF-mutant metastatic melanoma compared to historical treatments such as chemotherapy. Some serious adverse effects, including cutaneous squamous cell carcinoma, are attenuated with combination therapy, while less severe and reversible effects including pyrexia, left ventricular dysfunction, and ocular events can be more common with combination therapy. Existing data are insufficient to recommend triplet therapy, or a particular treatment sequence, with respect to BRAF and MEK inhibitors and immune therapies, though results from multiple ongoing trials are anticipated.

Broman, K.K., Dossett, L.A., Sun, J., Eroglu, Z., and Zager, J.S. Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings. 22286. 2019 Expert Opin Drug Saf.

Concepts Keywords
Adjuvant Chemotherapy
BRAF Binimetinib
Chemotherapy Dabrafenib
Clinical Trial Vemurafenib
Combination Therapy MEK inhibitor
Immunotherapy Benzamides
Left Ventricular Genentech
MEK Sulfonamides
Melanoma B-Raf inhibitor
Metastatic Cancer treatments
Mutant Clinical medicine
Neoadjuvant Organic compounds
Phase II Chemical compounds
Pyrexia Immunotherapy
Squamous Carcinoma Chemotherapy
Triplet Carcinoma
Vemurafenib Ventricular dysfunction
Neoadjuvant adjuvant applications

Semantics

Type Source Name
disease MESH multiple
disease MESH left ventricular dysfunction
disease DOID squamous cell carcinoma
disease MESH squamous cell carcinoma
drug DRUGBANK Binimetinib
drug DRUGBANK Encorafenib
drug DRUGBANK Cobimetinib
drug DRUGBANK Vemurafenib
drug DRUGBANK Trametinib
drug DRUGBANK Dabrafenib
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT MAP2K7
gene UNIPROT BRAF

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