Vemurafenib for the treatment of melanoma.

Abstract

INTRODUCTION:

Metastatic 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.

• Authors: Emmet John Jordan, Catherine M Kelly
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 13 Issue 17 Pg. 2533-43 (Dec 2012) ISSN: 1744-7666 [Electronic] England
• PMID: 23094782 (Publication Type: Journal Article, Review)

Chemical References

• Antineoplastic Agents
• Indoles
• Protein Kinase Inhibitors
• Sulfonamides
• Vemurafenib
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• Indoles (pharmacology, therapeutic use)
• Melanoma (drug therapy)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Proto-Oncogene Proteins B-raf (antagonists & inhibitors, genetics)
• Sulfonamides (pharmacology, therapeutic use)
• Vemurafenib