Authors' recommendations: In 2014, there were an estimated 76,100 new cases of malignant melanoma and approximately 9710 deaths from the disease in the United States. The overall 5-year survival rate for skin cancer is 90.9%, but median overall survival (OS) drops to 8 to 18 months in patients with metastatic melanoma, the most aggressive form of skin cancer. Until recently, treatment options for advanced melanoma were limited and relatively ineffective. In 2011, however, the Food and Drug Administration (FDA) approved novel therapies for melanoma that are targeted toward tumors with particular molecular characteristics. An early example was the BRAF inhibitor vemurafenib (proprietary name Zelboraf; Hoffman-LaRoche), reported to increase OS in metastatic melanoma patients who harbor an activating sequence variant in the B-Raf proto-oncogene, serine/threonine kinase (BRAF) gene. Common BRAF variants include p.Val600Glu (also known as V600E) and p.Val600Lys (also known as V600K). The cobas 4800 BRAF V600 Mutation Test (Roche Molecular Systems Inc.) was approved by the FDA for detection of the BRAF p.Val600Glu variant in patients with metastatic melanoma for treatment with vemurafenib. In May 2013, the FDA approved trametinib (proprietary name Mekinist) and dabrafenib (proprietary name Tafinlar), selective inhibitors manufactured by GlaxoSmithKline, as single agents for treatment of metastatic or unresectable (a tumor that cannot be surgically removed) melanoma harboring the BRAF p.Val600Glu variant (dabrafenib), or either the BRAF p.Val600Glu or p.Val600Lys variant (trametinib). In January 2014, the FDA issued approvals for a combination treatment using trametinib and dabrafenib in patients with advanced melanoma that is metastatic or unresectable when the tumor harbors a BRAF p.Val600Glu or p.Val600Lys variant. Trametinib is an inhibitor of mitogen-activated protein kinase (MEK) enzymes, key components in the mitogen-activated protein kinases (MAPK) signaling pathway. Increased activation of this pathway is a driving force in many cancers, including melanomas that have BRAF gene variants. In order to be treated with trametinib, tumor tissue of an affected patient must be positive for the BRAF p.Val600Glu and/or p.Val600Lys variant, as determined using an FDA-approved test. The THxID-BRAF kit (bioMérieux Inc.) was approved in May 2013 by the FDA to detect BRAF p.Val600Glu and p.Val600Lys variants.

Project Status: Completed

Year Published: 2014

URL for published report: The report may be purchased from: http://www.hayesinc.com/hayes/crd/?crd=17410

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: HAYES, Inc.

Contact Address: 157 S. Broad Street, Suite 200, Lansdale, PA 19446, USA. Tel: 215 855 0615; Fax: 215 855 5218

Contact Name: saleinfo@hayesinc.com

Contact Email: saleinfo@hayesinc.com

Copyright: 2014 Winifred S. Hayes, Inc