Sorafenib to Treat Patients with Radioactive Iodine-Refractory Differentiated Thyroid Cancer

Chicago—An international, multicenter, double-blind, randomized, phase 3 trial found that patients with radioactive iodine-refractory differentiated thyroid cancer who took sorafenib had a significant improvement in progression-free survival compared with patients who received placebo. The median progression-free survival was 10.8 months in the sorafenib group compared with 5.8 months in the placebo group (hazard ratio, 0.587; 95% confidence interval, 0.454-0.758; P<.0001).

Median overall survival of the patients has not yet been reached, according to Marcia S. Brose, MD, PhD, the study’s lead author, who presented the data during the plenary session at the ASCO meeting. Onyx Pharmaceuticals and Bayer HealthCare Pharmaceuticals, the drug’s marketers, supported the study.

Sorafenib, an oral multikinase inhibitor, is FDA approved to treat unresectable hepatocellular carcinoma and advanced renal cell carcinoma. Patients take two, 400-mg tablets twice daily with or without food.

Thyroid cancer is the most common type of endocrine cancer, and differentiated thyroid cancer accounts for approximately 85% of thyroid cancers diagnosed each year in the United States. In 2013, there will be an estimated 60,000 diagnoses of thyroid cancer in the United States, and 1850 people with the disease will die, according to Dr. Brose.

Most patients diagnosed with differentiated thyroid cancer are cured after receiving standard treatment consisting of surgery and radioactive iodine. However, approximately 5% to 15% of patients with differentiated thyroid cancer are resistant to radioactive iodine. The median survival for radioactive iodine-refractory patients is estimated at 2.5 to 3.5 years. As the disease progresses, patients have significant morbidity and frequent bone, pulmonary, and brain complications.

Dr. Brose said there are no treatment options available for patients with radioactive iodine-refractory differentiated thyroid cancer. The standard of care is palliative care, and, in recent years, patients have been referred to enter clinical trials.

In the DECISION (Study of Sorafenib in Locally Advanced or Metastatic Patients with Radioactive Iodine Refractory Thyroid Cancer) trial, the authors randomized 417 patients from October 2009 to July 2011 in a 1:1 ratio to receive 400 mg of sorafenib or placebo twice daily. The study was conducted at 89 centers in the United States, Europe, and Asia.

All patients had locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer, disease progression within the previous 14 months, adequate bone marrow, liver, and renal function, and an Eastern Cooperative Oncology Group performance status score of 0, 1, or 2. Exclusion criteria were prior chemotherapy, targeted therapy, or thalidomide and eligibility for surgery or radiotherapy with a curative intent.

The 2 groups were well balanced. Approximately half of patients in each arm were women, 60% were from Europe, and median age was 63 years.

When their disease progressed, patients in the placebo group were allowed to cross over and receive sorafenib. Of the 210 patients in the placebo group, 71 had crossed over to take sorafenib as of early June. An independent central review board assessed disease progression every 8 weeks.

Dr. Brose said there were no complete responses during the study, but 12.2% of patients in the sorafenib group and 0.5% of patients in the placebo group had partial responses, defined as tumor shrinkage ≥30% (P<.0001). Dr. Brose noted that although most patients did not have a partial response, the tumor shrinkage observed in many patients led to an alleviation of symptoms.

The median treatment duration was 46.1 weeks in the sorafenib group and 28.3 weeks in the placebo group. In addition, 77.8% of patients who took sorafenib had a dose modification compared with 30.1% of patients who received placebo. Further, 18.8% of patients discontinued sorafenib due to adverse events compared with 3.8% of the placebo group.

The most common treatment-emergent adverse events associated with sorafenib were hand-foot skin reaction, diarrhea, alopecia, rash, fatigue, weight loss, and hypertension. Dr. Brose noted that no new toxicities were observed, and that the adverse events were manageable with over-the-counter medications.