The U.S. Food and Drug Administration recently approved a new drug called vemurafenib (Zelboraf®, Roche) that targets some cases of melanoma, a deadly skin cancer, that has metastasized or cannot be removed surgically (unresectable). In addition, a companion genetic test that identifies individuals with this particular type of melanoma that may respond to therapy with the new drug was also approved (BRAF V600E Mutation Test).
Skin cancer is one of the most common types of cancer. Although melanoma comprises only 5% of skin cancers, it causes the most deaths. According to the most recent American Cancer Society estimates, there are more than 70,000 new cases of melanoma and 9,000 deaths from melanoma in the U.S. annually.
The newly FDA-approved test detects a mutation known as V600E in the BRAF gene, which codes for a signaling protein called B-raf that regulates cell growth. The test detects major BRAF gene mutations in cells from biopsied tissue, identifying those melanomas that may show response to vemurafenib. The BRAF V600E mutation occurs in about half of patients with melanoma.
The BRAF V600E genetic mutation can lead to an overactive B-raf protein, resulting in uncontrolled cell growth and decreased cell death and degradation. The mutation, which is acquired during a person's lifetime rather than inherited, is involved in about half of moles, birthmarks, and melanomas and confers a worse prognosis in patients with melanomas.
Vemurafenib inhibits the B-raf protein and proliferation of cancer cells. The drug is approved to treat late-stage melanoma that cannot be removed surgically and/or has spread to other parts of the body (known as metastatic melanoma). The FDA based its approval of the drug and the test on results of a study, published in the New England Journal of Medicine, of 647 patients with melanoma who had not received prior treatment and were identified with the new test as having the BRAF V600E mutation. An international team of researchers randomly assigned these patients to receive vemurafenib or standard chemotherapy with dacarbazine.
Results of the study show that vermurafenib improved overall survival and increased the time period from start of treatment that patients' cancers did not worsen (progression-free survival). At 6 months after the start of treatment, more patients treated with vemurafenib had survived (84%) compared with patients treated with standard chemotherapy (64%). Subsequently, an independent data and safety group recommended that patients receiving dacarbazine be switched over to vemurafenib.
Writing in Medscape Today News, nationally renowned oncologist Maurie Markman, MD, of Cancer Treatment Centers of America called the FDA's approval of the test and drug "a very important event in the oncology world." That’s not just because so many malignant melanoma patients have BRAF mutations, he continued. "I think the results of this trial and the approval by the FDA clearly demonstrate once again how we are entering a brand new era, and you can even call it a revolutionary era, where treatment will be based in oncology increasingly on demonstrated molecular abnormalities present within the tumors of patients. We are in the era of genomic medicine as it relates to cancer treatments."
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
U.S. Food and Drug Administration. Press release: FDA approves Zelboraf and companion diagnostic test for late-stage skin cancer. Available online at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm268241.htm through http://www.fda.gov. Issued August 17, 2011. Accessed October 5, 2011.
Chapman, P et al. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. New England Journal of Medicine 2011; 364:2507-2516. Available online at http://www.nejm.org/doi/full/10.1056/NEJMoa1103782 through http://www.nejm.org. Published online June 5, 2011. Accessed October 5, 2011.
Lowery-Nordberg, M. Melanoma BRAF Testing. Dermatopathology Newsletter. Delta Pathology. Issued July 26, 2011. Accessed October 5, 2011.
American Cancer Society. Melanoma Skin Cancer Overview. Available online at http://www.cancer.org/Cancer/SkinCancer-Melanoma/OverviewGuide/melanoma-skin-cancer-overview-key-statistics through http://www.cancer.org. Last reviewed May 5, 2011. Accessed Sept 20, 2011.
Markman, M. Broader Implications of Vemurafenib Approval. Medscape Today News. Available online at http://www.medscape.com/viewarticle/748749 through http://www.medscape.com. Posted September 7, 2011. Accessed October 6, 2011.
Roche Media Release (Basel, 17 August 2011). FDA approves Zelboraf (vemurafenib) and companion diagnostic for BRAF mutation-positive metastatic melanoma, a deadly form of skin cancer. Available online at http://www.roche.com/media/media_releases/med-cor-2011-08-17.htm through http://www.roche.com. Accessed October 2001.