E-Newsletter - October 2015

Pivotal Alliance Trials Address Two Rare Population Subsets
Trial for Hürthle Cell Thyroid Cancer  | Alliance A091302

Thyroid cancers of follicular origin consist of several histologic subtypes with diverse genetic and biologic features that directly influence clinical behavior and response to systematic therapies. Papillary thyroid cancer (PTC), representing 80 percent of all thyroid cancers, follicular thyroid cancer, and Hürthle cell thyroid cancer make up a group of malignancies known as differentiated thyroid cancer (DTC). DTCs can progress to more aggressive forms of disease categorized pathologically as poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), a rapidly progressive and fatal disease with less than one-year survival in most cases. Medullary thyroid cancers are not derived from follicular cells, but instead the parafollicular C-cells. These types of cancers are considered to be different than DTC.

The incidence of new thyroid cancers is the fastest growing among all cancers for both men and women with an estimated 62,450 new cases anticipated this year. 1 About 10-20 percent of thyroid patients develop distant metastasis.2,3 Surgical resection of recurrent and metastatic tumors, administration of radioactive iodine (RAI), and treatment with external beam irradiation are palliative therapeutic options for a subset of patients. Once tumors lose the ability to accumulate RAI and are not amenable to locoregional treatments, therapeutic options are quite limited as traditional chemotherapeutic agents are relatively ineffective.4 Doxorubicin is the only U.S. Food and Drug Administration (FDA) approved drug for the treatment of RAI-refractory thyroid cancer based on limited clinical data generated from the 1980s, and its efficacy is questionable. Treatment options for patients with recurrent and metastatic thyroid carcinoma not amenable to curative surgery or RAI are limited; no effective systemic therapy currently exists.

In Alliance A091302 (Randomized phase II study of sorafenib with or without everolimus in patients with radioactive iodine refractory Hürthle cell thyroid cancer), Alliance researchers will determine whether using everolimus along with sorafenib tosylate versus sorafenib tosylate alone in treating patients with advanced radioactive iodine refractory thyroid cancer will cause more shrinkage of thyroid cancer and prevent it from growing, and whether it could also cause more side effects than sorafenib tosylate alone.

This is a randomized study for patients with metastatic Hürthle cell thyroid cancer for whom radioactive iodine is found not to work. Participants will be randomized to either receive sorafenib alone or sorafenib in combination with the study drug, everolimus. If a patient receives sorafenib alone and the tumor starts to progress while on the drug, they can then “cross-over” and receive everolimus alone.

This study is based on a phase II study of sorafenib and everolimus in patients with metastatic thyroid cancer. In the study, nine patients had Hürthle cell thyroid cancer and seven of them had major responses to the combination. Preclinical data with Hürthle cell thyroid cancer suggest that the pathway by which everolimus inhibits is important for this type of tumor to grow.

The important eligibility criteria for the study includes: 1) a diagnosis of Hurthle cell thyroid cancer; 2) disease that is not curable through surgery or radiation therapy; and 3) no prior sorafenib use (although the prior use of other treatment such as pazopanib or lenvatinib is allowed). To learn more about this study, refer to the study protocol (Alliance A091302), which can be found on the CTSU menu (ctsu.org) and includes complete information on the trial design, treatment plan and patient eligibility. The Alliance Study Chair is Eric J. Sherman, MD, Memorial Sloan Kettering Cancer Center, e-mail: shermane@mskcc.org. Also see ClinicalTrial.gov Identifier: NCT02143726.

1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. (2015). SEER Stat Fact Sheets: Thyroid Cancer. Retrieved from http://seer.cancer.gov/statfacts/html/thyro.html
2. Durante C, Haddy N, Baudin E, et al: Long-term outcome of 444 patients with distant metastases from papillary and follicular thyroid carcinoma: benefits and limits of radioiodine therapy. J Clin Endocrinol Metab 91:2892-9, 2006
3. Fagin JA, Tuttle RM, Pfister DG: Harvesting the low-hanging fruit: kinase inhibitors for therapy of advanced medullary and nonmedullary thyroid cancer. J Clin Endocrinol Metab 95:2621-4, 2010
4. Pfister DG, Fagin JA: Refractory thyroid cancer: a paradigm shift in treatment is not far off. J Clin Oncol 26:4701-4, 2008


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For other articles in the October issue of Alliance E-News, see below.