AffiliationWaterford Regional Hospital, Department of Medical Oncology, Dunmore Road, Waterford, Ireland.
Drug Resistance, Neoplasm
Protein Kinase Inhibitors
Proto-Oncogene Proteins B-raf
MetadataShow full item record
CitationVemurafenib for the treatment of melanoma. 2012, 13 (17):2533-43 Expert Opin Pharmacother
JournalExpert opinion on pharmacotherapy
AbstractMetastatic melanoma is an aggressive disease resistant to chemotherapy. Recent clinical trials have reported improved survival for two novel agents; ipilimumab, a humanized, IgG1 monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and vemurafenib , a BRAF (v-raf murine sarcoma viral oncogene homolog B1) inhibitor targeting an activating mutation in the serine-threonine-protein kinase BRAF gene. AREAS COVERED: The authors reviewed preclinical and clinical data examining the safety of vemurafenib in melanoma. MEDLINE and EMBASE were searched using the medical subject heading 'vemurafenib' and the following text terms: melanoma, BRAF inhibition, vemurafenib. This review provides the reader with an overview of current data examining the efficacy and safety of vemurafenib in metastatic melanoma. EXPERT OPINION: Vemurafenib is an oral agent licensed for patients with BRAF V600E mutation-positive inoperable and metastatic melanoma. The most common adverse effects observed in Phase III clinical trials were dermatological events, arthralgia and fatigue. Specific dermatological toxicities included development of cutaneous squamous cell cancers and keratoacanthomas. Prolongation of the QT interval was also reported. Regular dermatological assessments and electrocardiograms are recommended. Ongoing trials are examining vemurafenib in both the adjuvant setting and metastatic setting in combination with ipilimumab and MEK inhibitors (mitogen-activated protein kinase/extracellular signal-regulated kinase). Understanding and overcoming mechanisms of resistance to BRAF inhibitors is the focus of ongoing research.
- Vemurafenib for the treatment of BRAF mutant metastatic melanoma.
- Authors: Martin-Liberal J, Larkin J
- Issue date: 2015
- Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma.
- Authors: Ravnan MC, Matalka MS
- Issue date: 2012 Jul
- Vemurafenib in patients with BRAF(V600) mutated metastatic melanoma: an open-label, multicentre, safety study.
- Authors: Larkin J, Del Vecchio M, Ascierto PA, Krajsova I, Schachter J, Neyns B, Espinosa E, Garbe C, Sileni VC, Gogas H, Miller WH Jr, Mandalà M, Hospers GA, Arance A, Queirolo P, Hauschild A, Brown MP, Mitchell L, Veronese L, Blank CU
- Issue date: 2014 Apr
- Novel ATP-competitive MEK inhibitor E6201 is effective against vemurafenib-resistant melanoma harboring the MEK1-C121S mutation in a preclinical model.
- Authors: Narita Y, Okamoto K, Kawada MI, Takase K, Minoshima Y, Kodama K, Iwata M, Miyamoto N, Sawada K
- Issue date: 2014 Apr
- Cutaneous manifestations of vemurafenib therapy for metastatic melanoma.
- Authors: Owen JL, Lopez IE, Desai SR
- Issue date: 2015 May