The first clinical trial orchestrated by ITOG has been completed, marking a major achievement for the group. This phase II trial, led by Dr. Manisha Shah from Ohio State University, found that patients who had progression of their thyroid cancer on a vascular endothelial growth factor receptor (VEGFR) inhibitor could benefit from treatment with cabozantinib. This work was recently published in the Journal of Clinical Oncology. https://www.ncbi.nlm.nih.gov/pubmed/28817373
Traditional treatments for differentiated thyroid cancer (DTC) include surgery, radioiodine (RAI), and suppression of thyroid stimulating hormone with levothyroxine. If these approaches fail, however, there are limited treatment options available. While treatment of such RAI-refractory disease remains a major therapeutic challenge, VEGFR inhibitors, including sorafenib and lenvatinib, have offered some hope for disease stabilization. Both agents recently have been FDA-approved for treatment in RAI-refractory disease. Unfortunately, for those patients with cancers that are resistant to VEGFR inhibitor treatments, there are no approved therapies. Correlative studies have revealed that the resistance to VEGFR inhibitors is at least in part due to the tyrosine kinase receptor cMET. Cabozantinib is an oral multikinase inhibitor that targets both cMET and VEGFR. This agent has been approved by the FDA for use in the treatment of medullary thyroid cancer. A phase I study demonstrated promising activity in differentiated thyroid cancer. It was therefore hypothesized that cabozantinib would be an effective treatment option for patients with DTC who progressed on first- or second-line VEGFR-targeted therapy.
Of the 25 eligible patients enrolled in the phase II, single-arm trial, an impressive 40% showed a partial response, indicating that cabozantinib can be used as a 2nd- or 3rd-line therapy in patients whose cancers progress after first-line VEGFR-targeted therapies. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Cabozantinib was generally well tolerated; the most common treatment-related adverse events were fatigue, weight loss, diarrhea, hand-foot syndrome, and hypertension. To our knowledge, this is the first trial evaluating the use of a multikinase inhibitor specifically after first- or second-line failure of prior VEGFR-targeted therapy.
ITOG's first clinical trial (NCT01811212) was conducted at six institutions (Massachusetts General Hospital, Mayo Clinic Jacksonville, Medstar Georgetown University Hospital, Ohio State University, University of Chicago Medical Center, University of Texas MD Anderson Cancer Center) by ITOG investigators. The study was coordinated by the Academic and Community Cancer Research United (ACCRU) and was partially funded by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI), a peer-reviewed federally-sponsored group. Additional funding for the clinical trial and correlative science was provided by ITOG. Besides its direct impact of establishing a new treatment option for our patients, this trial demonstrated that collaboration between these groups is feasible, paving the way for future such trials to be conducted. The completion of this study is one crucial step toward fulfilling the mission of ITOG's founding members to design, coordinate, and prioritize state-of-the-art clinical trials to catalyze a cure for thyroid cancer.