(ChemotherapyAdvisor) – The oral BRAF inhibitor vemurafenib (PLX4032; Zelboraf) induced a high rate of response in patients with previously treated BRAF V600-mutant metastatic melanoma, with a median overall survival nearly twice that currently observed, according to results of a multicenter Phase 2 trial in the February 23 issue of The New England Journal of Medicine.

Approximately 50% of melanomas harbor BRAF V600E mutant kinase, the investigators noted. In this study, patients received vemurafenib 960mg orally twice daily until disease progression or unacceptable toxicity. Median follow-up was 12.9 months.

Of the 132 patients treated, 6% had a complete response and 47% a partial response, for a confirmed overall response rate of 53%. Median overall survival was 15.9 months. Median duration of response was 6.7 months; median progression-free survival, 6.8 months; primary progression was observed in 14% of patients. Some patients responded after receiving vemurafenib for >6 months.

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Grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia were the most common adverse events observed. Cutaneous squamous cell carcinomas were diagnosed in 26% of patients; the majority was keratoacanthoma type.

“These results independently confirm the high response rate and response duration shown in a phase 1 trial. The long follow-up period in our study provides critical information on long-term overall survival, not yet shown in the phase 3 trial comparing vemurafenib with dacarbazine,” the investigators concluded.

Zelboraf, manufactured by Genentech, Inc., was approved by the U.S. Food and Drug Administration for use in BRAF V600E mutation positive metastatic melanoma in August 2011.


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