Development of encorafenib for BRAF-mutated advanced melanoma.

Article Details

Citation

Koelblinger P, Thuerigen O, Dummer R

Development of encorafenib for BRAF-mutated advanced melanoma.

Curr Opin Oncol. 2018 Mar;30(2):125-133. doi: 10.1097/CCO.0000000000000426.

PubMed ID
29356698 [ View in PubMed
]
Abstract

PURPOSE OF REVIEW: To describe the pharmacological properties, preclinical and clinical data of the novel V-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF)-inhibitor encorafenib (LGX818) and to compare these with established BRAF-inhibitors in the treatment of locally advanced or metastatic melanoma. RECENT FINDINGS: Encorafenib has shown improved efficacy in the treatment of metastatic melanoma in comparison with vemurafenib. Combination with the MEK inhibitor (MEKi) binimetinib allows for higher dose intensities of encorafenib further improving response rates (RRs). SUMMARY: Combination therapy with BRAF and MEKi has evolved as a standard of care in the treatment of locally advanced or metastatic BRAF-mutated melanoma. Despite compelling initial RRs, development of treatment resistance eventually leads to tumor progression in the majority of BRAF/MEK-inhibitor treated patients. Moreover, treatment-related adverse events are frequent, resulting in a substantial proportion of dose modifications and/or treatment discontinuations. The second-generation BRAF inhibitor encorafenib has been developed aiming at improved efficacy and tolerability through modifications in pharmacological properties. Clinical phase 3 data show improved progression-free survival both for encorafenib monotherapy and combination therapy with binimetinib compared with vemurafenib. Overall survival data and regulatory approval of this novel substance are eagerly awaited.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
EncorafenibSerine/threonine-protein kinase B-rafProteinHumans
Yes
Inhibitor
Details
Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
EncorafenibCytochrome P450 2C19ProteinHumans
No
Substrate
Details