FDA approves Zelboraf and companion diagnostic test for late-stage skin cancer

FDA has approved vemurafenib (Zelboraf, Genentech), the second melanoma drug this year to improve overall survival. Zelboraf is indicated for the treatment of patients with late-stage (metastatic) or unresectable melanoma, the most dangerous type of skin cancer.

Zelboraf is being approved with a first-of-a-kind test known as the cobas 4800 BRAF V600 Mutation Test, a companion diagnostic that will help determine whether a patient's melanoma cells have the BRAF V600E mutation.

Zelboraf is specifically indicated for the treatment of patients with melanoma whose tumors express a gene mutation known as BRAF V600E. The drug has not been studied in patients whose melanoma tested negative for that mutation through an FDA-approved diagnostic.

Normally involved in regulating cell growth, the BRAF protein is mutated in about half of the patients with late-stage melanomas. Zelboraf is a BRAF inhibitor with the capacity to block the function of the V600E-mutated BRAF protein.

"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, in a press release. Pazdur is director of the Office of Oncology Drug Products in FDA's Center for Drug Evaluation and Research.

In March, FDA approved ipilimumab (Yervoy, Bristol-Myers ), another new treatment for late-stage melanoma that also showed patients to live longer after receiving the drug.

Zelboraf was reviewed under FDA's priority review program, which provides for an expedited 6-month review of drugs that may offer major advances in treatment or that provide a treatment when no adequate therapy exists. Zelboraf and the companion BRAF V600E test are being approved ahead of the drug's Oct. 28, 2011 goal date and the companion diagnostics' Nov. 12, 2011 goal date.

Zelboraf's safety and effectiveness were established in a single international trial of 675 patients with late-stage melanoma with the BRAF V600E mutation who had not received prior therapy. Patients were assigned to receive either Zelboraf or dacarbazine, another anticancer therapy. The trial was designed to measure overall survival (the length of time between start of treatment and death of a patient).

The median survival (the length of time a patient lives after treatment) of patients receiving Zelboraf has not been reached (77% still living) while the median survival for those who received dacarbazine was 8 months (64% still living).

"Today's approval of Zelboraf and the cobas test is a great example of how companion diagnostics can be developed and used to ensure that patients are exposed to highly effective, more personalized therapies in a safe manner," said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostic Device Evaluation and Safety in FDA's Center for Devices and Radiological Health.

FDA's approval of the cobas 4800 BRAF V600 Mutation Test was based on data from the clinical study that also evaluated the safety and effectiveness of Zelboraf. Samples of a patient's melanoma tissue were collected to test for the mutation.

The most common side effects reported by patients receiving Zelboraf included joint pain, rash, hair loss, fatigue, nausea, and skin sensitivity when exposed to the sun. About 26% of patients developed cutaneous squamous cell carcinoma, which was managed with surgery. Patients treated with Zelboraf should avoid sun exposure.

Zelboraf is being approved with a Medication Guide to inform healthcare professionals and patients of Zelboraf's potential risks.

In July 2011, FDA issued a new draft guidance to facilitate the development and review of companion diagnostics. The guidance, currently available for public comment, is intended to provide companies with information on the agency's policy for reviewing a companion diagnostic and the corresponding drug therapy.

Melanoma is the leading cause of death from skin disease. The National Cancer Institute estimated that 68,130 new cases of melanoma were diagnosed in the United States during 2010; about 8,700 people died from the disease.