Chicago, IL—Sorafenib (Nexavar) has become the first drug in years to prove effective in the treatment of differentiated thyroid cancer (DTC) that has become resistant to radioactive iodine, according to phase 3 study results that were reported at the ASCO 2013 meeting.
DTC is the most common subtype of thyroid cancer, and its incidence is rising. DTC is rarely fatal, although up to 15% of patients become resistant to the current standard of care, radioactive iodine, and can die from the malignancy.
For this group, there has never been an effective treatment, said Marcia S. Brose, MD, PhD, Assistant Professor of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
“We have had no effective drugs for these patients for many years, so it is very exciting to have an oral drug that halts cancer growth for several months,” Dr Brose said at a press briefing. “This is the first time we have had a systemic treatment that can help them.”
Remission Prolonged by 5 Months
The 89-center Study of Sorafenib in Locally Advanced or Metastatic Patients with Radioactive Iodine Refractory Thyroid Cancer (DECISION) trial enrolled 417 patients who had become resistant to radioactive iodine. Patients were randomly assigned to sorafenib 400 mg twice daily or to placebo. On disease progression, the placebo recipients could cross over to receive sorafenib.
The median progression-free survival was 10.8 months in the sorafenib arm versus 5.8 months in the placebo arm, for a 42% reduction in mortality that was highly significant (P<.001). The median overall survival has not been reached in either arm, but a difference is unlikely to emerge, because 70% of patients have crossed over to receive active treatment, Dr Brose said.
Responses were observed in 12.2% of patients in the sorafenib arm versus in 0.5% of patients in the placebo arm. Stable disease was achieved by 42% of the patients receiving sorafenib, reflecting a disease control rate of 54% with the drug compared with 34% with placebo.
New Standard of Care?
Commenting on this study at the plenary session, Ezra Cohen, MD, Associate Professor of Medicine, University of Chicago, IL, commented, “These patients finally have options.” Dr Cohen was enthusiastic about the data, but he reminded oncologists that “not all iodine-refractory patients need treatment.”
He noted that 25% of placebo recipients did not progress during the trial, and in reality, most patients with radioactive iodine–refractory disease are asymptomatic. Dr Cohen said that the choice to use sorafenib should be based on the presence of symptoms, as well as on the location and growth rate of the disease.
He also noted that DTC that becomes refractory to vascular endothelial growth factor receptor inhibitors, such as sorafenib, “is an emerging entity that needs to be addressed.”