University of Pennsylvania Health System

Clinical Briefings™: Clinical Reports from Penn Medicine

Tuesday, March 16, 2010

Sorafenib for Differentiated Thyroid Cancer

Researchers at Penn Medicine played a critical role in the FDA approval of sorafenib (Nexavar®), for the treatment of metastatic, iodine-refractory thyroid carcinoma.
Led by Marcia S.Brose, MD, PhD, the research team included members of both the Abramson Cancer Center of the University of Pennsylvania and the Center for Head and Neck Cancer at Penn.

Radioactive iodine (RAI) is used to kill cancer cells in thyroid cancers that are not cured by surgery alone. As a part of standard therapy, RAI can be curative in the majority of patients with the disease.

Of patients with residual disease, however, up to 50% will become refractory to RAI. This occurs either because their cells can no longer absorb the radioactive iodine or because they have reached their lifetime maximum for radiation exposure.

Patients with RAI-refractory differentiated thyroid carcinoma (DTC) are essentially beyond the scope of standard treatment, and have an average lifespan of 2.5 to 3.5 years. Their disease is defined by continuous progression, resulting in pulmonary, bone and brain complications, among other concerns.

Thyroid cancer has been linked to several somatic mutations, including B-RAF V599E and the VEGF pathway. A multikinase inhibitor, sorafenib, was known to inhibit the expression of both mutations, but had not been evaluated in thyroid cancer before Dr. Brose and her colleagues at Penn treated a patient with RAI-refractory DTC with sorafenib in 2003. The patient’s response was remarkable, and led to a Phase II trial at Penn.

On the basis of clear evidence of efficacy, the Phase II study was concluded early and Dr. Brose was invited to become the principal investigator for the DECISION trial. This was a Phase III, double-blind, randomized study of sorafenib versus placebo in locally advanced or metastatic patients with RAI-refractory DTC.

The DECISION trial demonstrated significantly extended progression-free survival for patients taking sorafenib compared to placebo. The median PFS was 10.8 months among patients treated with sorafenib, compared to 5.8 months among patients receiving placebo. In 2013, sorafenib was approved by the FDA for the first-line treatment of metastatic and RAI-refractory differentiated thyroid cancer.

Case Study

Mr. K, a 37-year-old man, was referred to Penn Medicine by his internist after discovering a lump in his neck. His medical history was previously unremarkable.
At Penn, a needle aspiration biopsy determined that the lump was a follicular carcinoma.

Mr. K was scheduled for a thyroidectomy and bilateral central neck lymph node dissection. Of the 32 lymph nodes removed from Mr. K’s central and right lateral neck, 14 were positive for cancer.

A subsequent total body PET scan revealed lesions in his left lung and kidney. Mr. K was diagnosed with metastatic iodine-nonavid differentiated thyroid cancer. With an anticipated survival of approximately eight months, Mr. K agreed to participate in the Phase II clinical trial of sorafenib in thyroid cancer at Penn.

Within two months of initiating therapy at 400 mg bid, the progression of Mr. K’s disease stabilized; a marked decrease in both thyroglobulin levels and CT-documented tumor burden was noted.

At six months, Mr. K experienced palmar erythema, which responded well to anti-inflammatory agents; he had no other significant adverse effects during treatment. At 27 months post-treatment, his disease remained progression-free and he was otherwise healthy.

Faculty Team
The treatment of cancer at Penn Medicine involves more than 300 specialists and researchers collaborating under the auspices of the Abramson Cancer Center of the University of Pennsylvania, a national leader in cancer research, patient care, training, community education, and outreach.
At Penn, cancer patients are managed by oncologists, surgeons and radiation oncologists who specialize in the diagnosis and treatment of specific cancers; aftercare is tailored to address the emotional challenges facing cancer patients and their families––and all of these elements take place in a setting devoted to basic, translational, clinical and cancer control research.

Department of Otorhinolaryngology – Head and Neck Surgery
Marcia S. Brose, MD, PhD
Assistant Professor of Otorhinolaryngology
Director, Cancer Genetics Laboratory Abramson Cancer Center
Division of Endocrinology

Susan J. Mandel, MD, MPH
Director, Clinical Endocrinology and Diabetes,
Professor of Medicine

Head and Neck Oncology
Abramson Cancer Center
Perelman Center for Advanced Medicine, West Pavilion, 2nd Floor
3400 Civic Center Boulevard
Philadelphia, PA 19104

Currently Enrolling Thyroid Cancer Clinical Trials at the Abramson Cancer Center
Clinical research is a fundamental mission of the Abramson Cancer Center of the University of Pennsylvania. To determine whether a patient is eligible for a following trial, please visit and click on “Cancer Clinical Trials Matching” in the left-hand column.

A Phase II Trial of Cabozantinib for the Treatment of Radioiodine (RAI)-Refractory Differentiated Thyroid Carcinoma (DTC) in the First-line Setting
This is a Phase II, non-randomized, open-label study to determine the efficacy of cabozantinib as a first-line treatment for patients with differentiated thyroid cancer (DTC). Subjects will receive drug at a starting dose of 60mg PO QD, and can receive drug as long as they continue to derive clinical benefit or until they experience unacceptable drug-related toxicity.

A Randomised, Double Blind Study to Compare the Complete Remission Rate Following a 5-Week Course of Selumetinib or Placebo and Single Dose Adjuvant Radioactive Iodine Therapy in Patients With Differentiated Thyroid Cancer
This study is designed to evaluate the clinical efficacy, safety and tolerability of selumetinib with radioactive iodine therapy in patients with differentiated thyroid cancer. The primary outcome is complete remission in the study population.

An Expanded Access Program With Lenvatinib for the Treatment of Radioiodine-Refractory Differentiated Thyroid Cancer
This Expanded Access Program (EAP) consists of a pre-randomization Phase and a Randomization Phase. Only subjects with radioiodine-refractory DTC who fulfill the eligibility criteria will be treated. These subjects will be treated until progression of disease or unacceptable toxicity. Subjects must be radioiodine-refractory and must have histologically or cytologically confirmed diagnoses of one of the following DTC subtypes: a. Papillary thyroid cancer (PTC) i. Follicular variant ii. Variants (including but not limited to: tall cell, columnar cell, cribriform-morular, solid, oxyphil, Warthin's-like, trabecular, tumor with nodular fasciitis-like stroma, Hurthle cell variant of papillary carcinoma, poorly differentiated); b.Follicular thyroid cancer (FTC) i. Hurthle cell ii. Clear cell iii.Insular.

To refer a patient and/or consult with a physician, Call 800-789-PENN (7366) or visit:


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