Vemurafenib Joins Ipilimumab for Treating Metastatic Melanoma

October 2011, Vol 2, No 6 - FDA Approvals, News & Updates


The US Food and Drug Administration (FDA) approved the targeted therapy vemurafenib tablets (Zelboraf, Hoffmann-La Roche) for the treatment of patients with unresectable or metastatic mela noma with the BRAF V600E gene mutation. The BRAF V600E mutation occurs in 40% to 60% of patients with melanoma.

Vemurafenib received accelerated approval under the FDA’s priority review program, ahead of its October 28, 2011, regulatory date. “This has been an important year for patients with late-stage melanoma. Zelboraf is the second new cancer drug approved that demonstrates an improvement in overall survival,” said Richard Pazdur, MD, Director of the Office of Oncology Drug Products in the FDA.

In an international, randomized, open-label trial, 675 patients with previously untreated metastatic or unresectable melanoma with the BRAF V600E mutation received either vemurafenib 960 mg orally twice daily or dacarbazine (DTIC) 1000 mg/m2 intravenously every 3 weeks.

After a median follow-up of 6.2 months in the vemurafenib arm and 4.5 months in the dacarbazine arm, the overall survival rate was significantly greater with vemurafenib than with dacarbazine (P <.001), as was the progression-free survival (PFS) rate (P <.001).

The median survival of patients receiving vemurafenib had not been reached in the trial; it was 7.9 months for those receiving dacarbazine; median PFS rates were 5.3 months and 1.6 months, respectively. T

he most common adverse effects associated with vemurafenib were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, and nausea. Cutaneous squamous-cell carcinomas, including those of the skin and keratoacanthomas, were reported in 24% of patients receiving vemurafenib. Other reactions, sometimes severe, included hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, uveitis, QT prolongation, and liver enzyme laboratory abnormalities.

The recommended dose is 960 mg, taken every 12 hours, with or without a meal. Vemurafenib is approved with a medication guide and is not indicated for patients with the wild-type BRAF (ie, no mutation) melanoma. (August 17, 2011)