June 7th, 2011

BRAF Inhibitor Improves Melanoma Survival


Compared with standard chemotherapy, the investigational targeted therapy vemurafenib (also known as PLX4032) delayed the progression of advanced melanoma and improved overall survival. The results of this Phase III clinical trial were presented at the 2011 annual meeting of the American Society of Clinical Oncology.

Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. What makes melanoma so dangerous is that it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Approximately half of all melanomas carry a specific BRAF mutation known as V600E. Vemurafenib targets this mutation.

To evaluate vemurafenib in the treatment of advanced melanoma, researchers conducted a Phase III clinical trial among 675 patients with previously untreated, inoperable, Stage IIIC or Stage IV melanoma. The study was restricted to patients with a V600E mutation in the BRAF gene. Study participants were treated with either vemurafenib or the chemotherapy drug dacarbazine.

  • Compared with patients in the chemotherapy group, patients in the vemurafenib group had a 63% reduction in risk of death and a 74% reduction in risk of melanoma progression.
  • Tumor shrinkage occurred in 48.4% of patients in the vemurafenib group and 5.5% of patients in the dacarbazine group.
  • Less than 10% of patients in the vemurafenib group experienced severe side effects (grade 3 or worse). The most common side effects of vemurafenib were skin rashes, sensitivity to light, and joint pain.

In a prepared statement, the lead author of the study concluded “This is really a huge step toward personalized care in melanoma. This is the first successful melanoma treatment tailored to patients who carry a specific gene mutation in their tumor, and could eventually become one of only two drugs available that improves overall survival in advanced cancers.” The other drug that has improved melanoma outcomes is Yervoy™ (ipilimumab).

Reference: Chapman PB, Hauschild A, Robert C et al. Phase III randomized, open-label, multicenter trial (BRIM3) comparing BRAF inhibitor vemurafenib with dacarbazine (DTIC) in patients with V600E BRAF-mutated melanoma. Paper presented at: 2011 Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA4.

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Tags: Melanoma, News, Stage III Melanoma, Stage IV Melanoma, Uncategorized