April 24, 2014
Penn Medicine Study: Sorafenib Shows Success in Advanced Differentiated Thyroid Cancer Patients
Results of Randomized Phase III Clinical Trial Led to FDA Approval of Drug
PHILADELPHIA — The kidney and liver cancer drug sorafenib holds metastatic thyroid cancer at bay for nearly twice as long as a placebo, according to a new study from researchers in the Abramson Cancer Center at the University of Pennsylvania published in the journal Lancet. This is the first effective treatment for thyroid cancer patients who progress following standard treatments.
Preliminary results of this randomized phase III trial were presented at a plenary session during the American Society of Clinical Oncology’s annual meeting in 2013.
Based on these data, sorafenib was approved by the U.S. Food and Drug Administration (FDA) in November 2013 for patients with locally recurrent or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine treatment. These patients previously had limited approved treatment options.
Thyroid cancer is highly curable through surgery and radioactive iodine treatment, but about 10 percent of the 60,000 patients who are diagnosed with the disease each year fail to respond to standard therapies, with tumors eventually appearing in the lungs, lymph nodes, bones and other sites. The only other drug for advanced thyroid cancer, doxorubicin, which was approved in 1974, is not used because it is highly toxic and is not effective.
“Until we began using sorafenib, we had no effective treatment options for these patients who suffered due to progression of their disease,” said Marcia S. Brose, MD, PhD, an assistant professor in the department of Otorhinolaryngology: Head and Neck Surgery in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania, who led the study, which is known as DECISION. “Now, we can give patients hope – a breakthrough medication that can stop the progression of the disease for an average of five months. This trial is the first step in a promising series of clinical trials to identify new drugs that are shifting the horizon for patients with advanced differentiated thyroid cancer.”
Of the 417 metastatic thyroid cancer patients studied in the multicenter, international trial, 207 were randomized to take sorafenib, an oral drug, and 210 to a placebo arm. The study met its primary endpoint showing that among patients taking sorafenib, median progression-free survival was 10.8 months, compared to 5.8 months among the placebo group.
Twelve percent of patients experienced tumor shrinkage in the sorafenib arm, compared to 0.5 percent of patients taking a placebo. Importantly, the therapy also appeared to thwart disease progression even among many of those whose tumors did not achieve partial response: 42 percent of patients who took sorafenib had stable disease after six months, compared to 33 percent of those in the placebo group.
The most common adverse events observed among patients taking sorafenib included hand-foot skin reaction, diarrhea, alopecia, rash, fatigue, weight loss and hypertension, all of which are manageable and consistent with findings from previous trials of the drug for its approved indications.
The study also showed that sorafenib improves progression free survival across all subgroups and in patients irrespective of the BRAF or RAS mutations—which are common in patients with radioactive iodine refractory differentiated thyroid cancer. Thus, those mutations are not predictive biomarkers for cancers treated with sorafenib.
“Sorafenib is the first effective and well tolerated drug to improve the outcomes for patients with radioactive iodine refractory and progressing differentiated thyroid cancer, and as such represents the new standard of care for patients that suffer from this this disease,” said Brose.
Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals provided funding for the trial.
Editor’s note: Dr. Brose has received consulting fees and honoraria from these companies.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $392 million awarded in the 2013 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2013, Penn Medicine provided $814 million to benefit our community.