(ASCO, June 2, 2013) A large phase III clinical trial reported that sorafenib improves progression free survival for patients with radioactive iodine refractory, differentiated thyroid cancer.

June 2, 2013 marks a major milestone in thyroid cancer, as ITOG member Marcia Brose, MD, PhD, Assistant Professor of Medicine, Hematology/Oncology and of Otolaryngology and Head and Neck Surgery in the Abramson Cancer Center and Perelman School of Medicine at the University of Pennsylvania in Philadelphia, presented the results from the DECISION trial, the first randomized, phase III clinical trial of systemic therapy in patients with differentiated thyroid cancer (DTC) resistant to radioactive iodine therapy (RAI)*. Dr. Brose presented the results of DECISION in the plenary session at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago. This international study showed that sorafenib (Nexavar) improves progression-free survival (PFS) in RAI-refractory DTC, a disease for which there has been no FDA-approved new therapy for the last 40 years.

DTC is the most common type of thyroid cancer, accounting for about 85% of cases each year. Although DTC generally has high cure rates following surgery and RAI, some patients will develop RAI-resistant disease. The only FDA-approved treatment is doxorubicin, which is rarely used because of low efficacy and high toxicity. 

Sorafenib is an oral multikinase inhibitor that targets VEGF receptor kinases 1-3 and Raf, which control cell division and new blood vessel formation. At present, sorafenib is FDA-approved for advanced kidney cancer and liver cancer.

In the DECISION study, 417 patients with RAI-resistant DTC that had progressed within the past 14 months were randomly assigned to receive sorafenib or placebo. Patients in the placebo control arm were allowed to cross over to the sorafenib arm upon disease progression. The primary endpoint was PFS, which was 10.8 months with sorafenib vs 5.8 months with placebo (hazard ratio=0.58; 95% CI, 0.45–0.75; p<.0001). Tumor shrinkage of at least 30% was achieved in 12.2% of patients on sorafenib, and an additional 42% of patients had stable disease for at least six months. Thus, the disease control rate with sorafenib was 54%, compared to 34% in the placebo arm. Overall survival data are not yet mature, but are anticipated to be impacted by cross over from placebo to sorafenib.

While sorafenib, made by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals, which funded the study, has now has proven benefits in RAI-resistant DTC, it is associated with side effects, the most common of which include hand-foot syndrome, diarrhea, rash, fatigue, weight loss, and hypertension. These and more rare side effects require that patients and providers weigh the potential risks and benefits prior to starting therapy.

It is expected that the DECISION trial will form the basis for a supplemental New Drug Application to the FDA later this year.

*Brose MS, Nutting C, Jarzab B, et al. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. J Clin Oncol. 2013;31(suppl; abstr 4).