Mutations in a gene that codes for the enzyme BRAF kinase have been associated with increased risk for papillary thyroid cancer (PTC). An early-stage clinical trial of the BRAF inhibitor vemurafenib resulted in either a partial response or stable disease in patients with PTC and BRAF mutations.
R. Dadu and colleagues from M. D. Anderson Cancer Center, Houston, TX, will report on a series of patients with advanced metastatic PTC and the V600E BRAF mutation who were treated with the selective BRAF inhibitor vemurafenib in a poster presentation at the upcoming 83rd Annual Meeting of the American Thyroid Association, October 16-20, in San Juan, Puerto Rico.
Three of 12 patients (25%) had a partial response to treatment (>30% reduction) and 75% had stable disease (of which 56% had a minor response) to treatment. In the poster "Efficacy and Tolerability of Vemurafenib in BRAFV600E Positive Papillary Thyroid Cancer (PTC)" the researchers report that the treatment was well tolerated.
BP Danysh and coworkers from M. D. Anderson Cancer Center explore why responses to vemurafenib are typically incomplete, drug resistance develops, and a patient's disease inevitably progresses despite treatment. In the poster "Effects of Activated Estrogen Receptors on Acquired BRAF Inhibitor Resistance in Papillary Thyroid Cancer (PTC)" they describe the role that estrogen receptors may have in acquired resistance to BRAF inhibitors. This may help explain the gender disparity in PTC (3:1 female:male ratio) and why the cancer is more prevalent among women of childbearing age.
Nearly 50% of papillary thyroid cancers in the U.S. are BRAF V600E mutation positive, and this characteristic has been exploited with the development of novel small molecule therapies that target BRAF for treating patients with advanced thyroid cancer," says Julie Ann Sosa, MD, Program Committee Co-Chair; Professor of Surgery and Medicine, Chief, Section of Endocrine Surgery, and Director of Health Services Research, Department of Surgery, Duke University School of Medicine; and Leader, Endocrine Neoplasia Diseases Group, Duke Cancer Institute and Duke Clinical Research Institute, Durham, NC. "Unfortunately, treatment effect can be short-lived. These emerging data regarding vemurafenib, a BRAF-targeted inhibitor used with good effect for BRAF V600E mutation positive melanomas, are much anticipated. Additional information regarding estrogen receptors and the extent of effect of BRAF-targeted inhibitors could be helpful in moving forward the development of new combinations of agents with more durable effect."
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