Search Results

You are looking at 1 - 2 of 2 items for

  • Author: Jennifer A. Sipos x
  • Refine by Access: All x
Clear All Modify Search
Full access

Dwight H. Owen, Bhavana Konda, Jennifer Sipos, Tom Liu, Amy Webb, Matthew D. Ringel, Cynthia D. Timmers, and Manisha H. Shah

BRAF V600E mutations occur in approximately 40% of all patients with papillary thyroid cancer (PTC) and are associated with a worse prognosis in population studies. Treatment with single-agent BRAF inhibitors can result in nondurable partial responses (PRs) in clinical trials, but resistance inevitably develops. The mechanisms of resistance are not completely understood, but in non-thyroid tumors harboring BRAF V600E mutations, resistance has been ascribed to concurrent or acquired mutations in MEK1/2, RAC1, KRAS, and NRAS. This case report describes a patient with radioactive iodine–refractory metastatic PTC treated in a clinical trial with combination BRAF and MEK inhibition who achieved a durable PR. At time of progression, biopsy revealed an acquired KRAS G12V–activating mutation. The patient subsequently went on to have a PR to cabozantinib therapy in the clinical trial. This is the first reported case of an acquired KRAS-activating mutation that developed during treatment with BRAF and MEK inhibition in a patient with BRAF-mutated PTC. The KRAS mutation was also detected in peripheral blood samples taken as part of the trial, indicating that resistant mutations may be identified through noninvasive means. The identification of resistant mutations in patients at time of progression is necessary to identify possible therapeutic options including potential clinical trials.

ClinicalTrials.gov identifier: NCT01723202

Full access

Robert I Haddad, Lindsay Bischoff, Douglas Ball, Victor Bernet, Erik Blomain, Naifa Lamki Busaidy, Michael Campbell, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Whitney S. Goldner, Theresa Guo, Megan Haymart, Shelby Holt, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Dominick M. Lamonica, Susan Mandel, Stephanie Markovina, Bryan McIver, Christopher D. Raeburn, Rod Rezaee, John A. Ridge, Mara Y. Roth, Randall P. Scheri, Jatin P. Shah, Jennifer A. Sipos, Rebecca Sippel, Cord Sturgeon, Thomas N. Wang, Lori J. Wirth, Richard J. Wong, Michael Yeh, Carly J. Cassara, and Susan Darlow

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).