alexa Vemurafenib in patients with BRAF V600E mutation-positive advanced melanoma.
Genetics & Molecular Biology

Genetics & Molecular Biology

Journal of Molecular Biomarkers & Diagnosis

Author(s): Ravnan MC, Matalka MS

Abstract Share this page

Abstract BACKGROUND: Vemurafenib is an oral, small-molecule kinase inhibitor that selectively targets activated BRAF V600E and has been approved for the treatment of advanced BRAF mutation-positive melanoma. OBJECTIVE: This article reviews the clinical pharmacology, efficacy, tolerability, and pharmacokinetics of vemurafenib and in addition outlines proposed mechanisms of vemurafenib resistance. METHODS: A literature search of MEDLINE and ScienceVerse Scopus was performed using the key words malignant melanoma, BRAF, vemurafenib, and PLX4032. Scientific abstracts, US Food and Drug Administration Web site data (www.accessdata.fda.gov), the manufacturer-submitted approval data from ClinicalTrials.gov (www.clinicaltrials.gov), and the references from applicable publications were also consulted. RESULTS: Clinical studies have reported that vemurafenib is efficacious and acceptably well-tolerated. In a Phase I study (BRIM-1), a 960-mg BID dose achieved an objective response rate of 81\% among 32 patients with melanoma who carried a BRAF V600E mutation. Of the 26 responders, 2 achieved a complete response and 24 a partial response. In BRIM-2, 132 BRAF V600E-positive patients achieved an overall response rate of 53\% (95\% CI, 44\%-62\%); 6\% achieved a complete response and 47\%, a partial response. Response was noted at 6 weeks and lasted a median of 6.7 months (95\% CI, 5.6-8.6). Median survival was 15.9 months (95\% CI, 11.6-18.3); 77\% of patients survived to 6 months (95\% CI, 70-85) and 58\% to 12 months (95\% CI, 11.6-18.3), and an estimated 43\% were expected to survive to 18 months (95\% CI, 33-53). The Phase III study (BRIM-3) compared vemurafenib to dacarbazine. The hazard ratio (HR) for death with vemurafenib was 0.37 (95\% CI, 0.26-0.55; P < 0.001). At 6 months, overall survival was 84\% (95\% CI, 78-89) versus 64\% (95\% CI, 56-73) in the vemurafenib and dacarbazine treatment arms, respectively. The HR for tumor progression in the vemurafenib cohort was 0.26 (95\% CI, 0.20-0.33; P < 0.001), and the estimated median progression-free survival was 5.3 months with vemurafenib versus 1.6 months with dacarbazine. Finally, the difference in response rates was significant (48\% vs 5\%, respectively; P < 0.001). The most common adverse events reported have been arthralgia, rash, photosensitivity, fatigue, pruritus, alopecia, cutaneous squamous cell carcinoma, diarrhea, and mild to moderate nausea. CONCLUSIONS: Vemurafenib is effective for advanced melanomas expressing the BRAF V600E mutations. Resistance to BRAF inhibition can be problematic, but new evidence suggests that combination therapy may attenuate the issue. Targeting the cellular activity of melanoma cells is reported to be efficacious and is expected to delay progression and prolong survival. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved. This article was published in Clin Ther and referenced in Journal of Molecular Biomarkers & Diagnosis

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords