Vemurafenib Study Builds on Positive Response Data

Sanjiv S. Agarwala, MD

Professor of Medicine

Temple University School

of Medicine

Chief, Oncology /Hematology

St. Luke’s Hospital and Health Network Bethlehem, PA

Vemurafenib (Zelboraf) continues to demonstrate clinical response and overall survival (OS) benefits for patients with metastatic melanoma, according to a recent trial with a long-term follow-up period.

In the phase II trial, vemurafenib delivered an overall response rate, the primary endpoint of the study, in >50% of 132 patients with BRAF V600-mutated metastatic melanoma. The median OS, a secondary endpoint, was 15.9 months (95% confidence interval [CI], 11.6-18.3). Historically, patients diagnosed with metastatic melanoma survive an average of 6 to 10 months.

Patients in the study were followed for a median period of 12.9 months (range, 0.6-20.1). The study found that 8 patients (6%) achieved a complete response and 62 patients (47%) achieved a partial response for an overall response rate of 53% (95% CI, 0.44 -0.62). The median duration of response was 6.7 months (95% CI, 5.6-8.6), and the median length of progression-free survival (PFS) was similar at 6.8 months (95%, 5.6-8.1). At the time of data cut-off, 33 patients (25%) had not progressed.

While these data were expected, they strengthen the status of vemurafenib as a go-to treatment for patients with metastatic melanoma, according to Sanjiv S. Agarwala, MD. He noted that the median OS data were particularly encouraging. “That’s the biggest number we’ve seen in melanoma survival yet,” Agarwala said.

Investigators said some of the patients were treated for up to 6 months before showing any sign of response. However, Agarwala noted that even if it took months to observe a response to the drug, the fact that the disease was stable in those patients is significant in its own right.

“Stable disease is still a very important clinical benefit in these patients,” Agarwala said.

Vemurafenib, an oral small molecule, was approved by the FDA in August 2011 for the treatment of patients with unresectable or metastatic melanoma with the BRAF V600 mutation. A DNA-based companion diagnostic, the cobas 4800 BRAF V600 Mutation Test, was approved along with it.

Plexxikon, a member of Daiichi Sankyo Group, and Genentech, a member of the Roche Group, are working together to develop and promote the drug.