The targeted agent Tafinlar® (dabrafenib) produced a high response rate in patients with metastatic melanoma with a BRAF-V600E mutation, according to the results of a study published in the Journal 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. Melanoma is dangerous because it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.
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. This mutation produces an abnormal version of the BRAF protein that stimulates cancer growth. Some melanomas carry another BRAF mutation known as V600K.
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Targeted therapies provide an opportunity to deliver more individualized and more effective cancer therapy. Tafinlar is a targeted therapy known as a kinase inhibitor that targets the BRAF mutation.
Researchers conducted a single-arm, multicenter study that included 76 patients with BRAF-V600E and 16 patients with BRAF-V600K mutant metastatic melanoma. All patients received oral Tafinlar (150 mg twice daily) until disease progression, death, or unacceptable toxicity. The primary endpoint was overall response rate in BRAF-V600E mutant patients. The study also assessed the ability of tumor-specific circulating cell-free DNA (cfDNA) to predict outcome.
Among patients with a BRAF-V600E mutation, 59 percent of patients had a confirmed response, including 7 percent with complete responses. The median progression-free survival in this group was 6.3 months and median overall survival was 13.1 months.
Among patients with a BRAF-V600K mutation, 13 percent had a confirmed partial response. Median progression-free survival in this group was 4.5 months and median overall survival was 12.9 months.
The researchers could not find a clear explanation for the difference in response rate between patients with BRAF-V600E and BRAF-V600K.
Use of the cfDNA assay showed that increasing baseline BRAF-V600E mutation fraction was associated with reduced response rate and progression-free survival.
The most common adverse events were arthralgia (33%), hyperkeratosis (27%), and pyrexia (24%). Overall, 27 percent of patients experienced a serious adverse event and 10 percent of patients had squamous cell carcinoma.
The researchers concluded that Tafinlar was well tolerated and clinically active in patients with BRAF-V600E/K mutant metastatic melanoma. What’s more—they note that cfDNA may be a useful prognostic and response marker in future studies.
Ascierto PA, Minor D, Ribas A, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. Journal of Clinical Oncology. Published early online August 5, 2013. doi: 10.1200/JCO.2013.49.8691
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