BRAF and Melanoma: Taking It Personally

In This Article

Abstract and Introduction

Abstract

More than 80% of melanoma patients with an activating mutation in BRAF responded to treatment with PLX4032.

Introduction

Ever since researchers first described the role of BRAF mutations in melanoma, we have eagerly awaited a clinically effective anti-BRAF drug. A recent multicenter trial of a new agent seems to be the first step toward personalized medicine for melanoma. Investigators conducted a dose-escalation trial, with an extension phase, of PLX4032, an orally available kinase inhibitor of mutated BRAF; the co-developers of this agent supported the research. Fifty-five patients (49 with melanoma) were enrolled in an initial dose-escalation phase; another 32 patients with metastatic melanoma and tumors harboring the BRAF ^V600E mutation were enrolled in an extension phase.

In the first phase, the investigators analyzed antitumor activity and dose-limiting toxicity to arrive at a dose of 960 mg twice daily for the extension phase. Cutaneous squamous cell carcinomas (SCCs) occurred in 8 (15%) and 10 (31%) of the patients in the dose-escalation and extension cohorts, respectively, (median onset, 8 weeks). All but one of the SCCs were or had features of keratoacanthoma, and none required therapy discontinuation. Sixteen patients in the first phase harbored the BRAF ^V600E mutation; 11 (69%) had a response, 10 partial and 1 complete. Patients without BRAF mutations showed no evidence of tumor regression; four had progressive disease within the first 2 months of treatment. The extension phase included only patients with the BRAF ^V600E mutation. Of these 32 patients, 26 (81%) had a response, 2 complete and 24 partial. The estimated median progression-free survival among these patients at the time of analysis was more than 7 months.

Cite this: BRAF and Melanoma: Taking it Personally - Medscape - Sep 27, 2010.

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