Improved Survival With Vemurafenib in Melanoma

In This Article

Abstract and Introduction

Abstract

Patients with unresectable melanoma and the BRAF V600E mutation saw rapid response and improved rates of overall and progression-free survival.

Introduction

From the moment that the BRAF V600E mutation was first associated with melanoma, nearly 10 years ago, this large, phase 3 trial of vemurafenib (PLX4032), a potent inhibitor of mutated BRAF, has been in the making. The brisk march of this drug from benchside to bedside was marked by positive indicators along the way: A phase 1 trial established the maximum tolerated dose and found consistent tumor responses, and a phase 2 trial (BRIM-2; J Clin Oncol 2011; 29:S8509) showed a response rate of 53% and a median response duration of 6.7 months.

Investigators conducted an open-label, multicenter clinical trial in patients with untreated, unresectable stage IIIc or IV melanoma and a BRAF V600E mutation. Patients were randomly assigned to vemurafenib (960 mg orally, twice daily) or dacarbazine (the only FDA-approved chemotherapeutic for metastatic melanoma). In 672 evaluable patients, overall survival at 6 months was 84% with vemurafenib and 64% with dacarbazine — high survival rates that reflect the short follow-up. In fact, the trial was terminated early after an interim analysis showed a significant survival difference. The hazard ratio for tumor progression with vemurafenib was 0.26. The estimated median progression-free survival was 5.3 months in vemurafenib recipients and 1.6 months with dacarbazine. Nearly half of vemurafenib recipients met RECIST criteria for tumor response, versus <10% of dacarbazine recipients. Cutaneous squamous cell carcinomas and keratoacanthomas were among the most common adverse effects.

Cite this: Improved Survival with Vemurafenib in Melanoma - Medscape - Jun 06, 2011.

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