Kinase inhibitors target advanced thyroid cancer

Recent discoveries about the genetics and cell signaling pathways of thyroid tumors have lead to the development of kinase inhibitors that target tumor cell division and blood vessels. These new approaches showed great promise in results from two recent clinical trials presented at the 2013 European Cancer Congress in Amsterdam, The Netherlands.

The first study provides newly released data from the phase III DECISION trial of the drug sorafenib, a kinase inhibitor already approved for the treatment of kidney and liver cancers. Lead author Marcia Brose, MD, PhD, of the Abramson Cancer Center of the University of Pennsylvania, and her colleagues examined the effectiveness of sorafenib on thyroid cancers that harbor BRAF and RAS mutations. They previously reported that for patients who received sorafenib, progression-free survival was 10.8 months versus 5.8 months in the placebo arm. The most common mutations for the enrolled patients were found in the BRAF and RAS genes, but all groups, regardless of the presence of a BRAF and RAS mutation, benefited from treatment with sorafenib.

"Our results are important because they show that regardless of the presence of these two common genetic changes, the group that was treated with sorafenib did better than the placebo," Brose says. "There was no subgroup that did not appear to benefit from the intervention with sorafenib." The use of sorafenib as first line treatment for advanced differentiated thyroid cancer is now undergoing evaluation for FDA approval, which would represent the first effective drug for patients with advanced thyroid cancer in more than 40 years.

The second study Brose presented focused on the subgroup of patients with papillary thyroid cancer (PTC), which is the most prevalent form of advanced thyroid cancer. About half of PTC patients harbor the BRAFV600E mutation, which is also present in melanomas that can be successfully treated with BRAF inhibitor drugs.

"In this phase II study, we took the BRAFV600E inhibitor, vemurafenib, and studied it in BRAF-mutated papillary thyroid cancer patients to see if there's an effect," Brose explained. Approximately 50 patients with the BRAFV600E mutation were enrolled in the study, all with progressive PTC that had failed to respond to radioactive iodine treatment. The patients were divided into two groups: one that had not received sorafenib or other similar kinase inhibitor, and one that had.

The progression free survival of the treatment naïve group was 15.6 months and had a response rate of 35%, while the progression free survival in the previously treated group was 6.3 months with a response rate of 26%. "Our results show that we can effectively treat PTC patients [who] have progressive disease by targeting a common mutation, and produce clinically meaningful periods of progression free survival," Brose said. Taken together, the two trials offer substantial new hope for patients with progressive thyroid cancer.

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