ASCO 2013: Sorafenib Stalls Growth of Treatment-resistant Differentiated Thyroid Cancer
A randomized phase III study found that the targeted drug sorafenib (Nexavar) stalls disease progression by 5 months in patients with metastatic differentiated thyroid cancer that has progressed despite standard radioactive iodine therapy. If approved in this setting by the U.S. Food and Drug Administration (FDA), sorafenib would become the first new active drug for this form of thyroid cancer in 40 years.
The results of the trial were announced at the 2013 ASCO Annual Meeting (Abstract 4). “After having no effective drugs for these patients for so many years, it is very exciting to find an oral drug that stops growth of the cancer for several months,” said the study’s lead author Marcia Brose, MD, PhD. “For these patients, a longer progression-free survival means more months without hospitalization and invasive procedures to control pain and other symptoms. This is the first time we have had a systemic treatment that can help.” Dr. Brose is Assistant Professor of Otolaryngology and Head and Neck Surgery in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
Resistance to Radioactive Iodine Therapy
Although differentiated thyroid cancer generally has high cure rates following standard treatment with surgery and radioactive iodine, roughly 5% to 15% of patients develop radioactive iodine resistance. “Once this happens, the overall survival for these patients drops to 2.5 to 3.5 years,” Dr. Brose said. “There is also significant morbidity, with frequent bone, pulmonary, and brain complications.”
The only approved treatment for patients who develop radioactive iodine resistance is doxorubicin, which is rarely used due to its low efficacy and high toxicity. This is the first time a kinase inhibitor has been assessed for this indication in a large clinical trial. Since the disease will eventually progress after sorafenib treatment in most patients, additional treatment options still need to be developed for use as second-line agents and beyond.
Study Design
The DECISION study, an international, multicenter trial with 89 participating centers across the United States, Asia, and Europe, enrolled patients with radioactive iodine–resistant, locally advanced or metastatic differentiated thyroid cancer. Among the 417 patients randomly assigned to sorafenib orally at 400 mg or placebo, 96% had metastatic disease. Patients in the placebo arm were allowed to cross over to the sorafenib arm upon disease progression.
The median age of the patients was 63 years, and 52% were female. Tumor histology by independent assessment was 57% papillary, 25% follicular, and 10% poorly differentiated.
Disease Control Rate
“DECISION met the primary endpoint of extending progression-free survival,” Dr. Brose reported. The median progression-free survival was 10.8 months in the sorafenib group vs 5.8 months in the placebo arm (P < .0001). An additional 42% of patients in the sorafenib arm had stable disease for 6 months or longer, resulting in a disease control rate of 54% vs 34% in the placebo group. Overall survival data are not yet mature.
“There were no complete responses observed in this study. Partial responses were observed in 12.2% of patients on the sorafenib arm compared to 0.5% on the placebo arm, and this was statistically significant [P < .0001],” Dr. Brose said. “While tumor shrinkage for many patients did not reach 30%—the cutoff for partial responses—the shrinkage observed was often sufficient to alleviate symptoms in symptomatic patients,” she added.
“Now we have an option where we know that we can prolong progression-free survival, and using this for our patients becomes a very attractive option,” noted Gregory A. Masters, MD, FACP, Director, Medical Oncology Fellowship, at the Helen F. Graham Cancer Center in Newark, Delaware. “I think, yes, it will become the standard of care.”
Manageable Adverse Effects
“The adverse effects for sorafenib were manageable,” Dr. Brose said, and most of the time were relieved by over-the-counter medications. The most common adverse events were hand-foot skin reaction, diarrhea, alopecia, rash, fatigue, weight loss, and hypertension. “No new toxicities were observed,” Dr. Brose added.
Further analysis of data from this clinical trial is planned to find markers that would help identify patients who respond well to sorafenib and those who may need additional therapy.
Sorafenib is a multitargeted drug that blocks two distinct proteins—Raf kinase and vascular endothelial growth factor (VEGF) receptor kinase. The drug is already approved by the FDA for the treatment of advanced kidney cancer and inoperable liver cancer.
This research was supported in part by Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals. Dr. Brose reported a consultant or advisory role with Onyx and Bayer, honoraria from Bayer, and research funding from Bayer.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
