Advanced Differentiated Thyroid Cancer:

Targeted, Multireceptor Kinase Inhibition to
Slow Disease Progression and Prolong Progression Free Survival


The intended audience for this activity is endocrinologists, medical oncologists, and primary care physicians who wish to broaden and update their knowledge of the management and treatment of locally advanced or metastatic differentiated thyroid cancer.


Differentiated thyroid cancer (DTC) has a generally good prognosis, but median survival for patients with advanced, radioactive iodine-refractory (RAI-R) DTC and distant metastases is estimated to be 3 to 6 years. Unfortunately, effective treatments for these patients have been lacking. Thus, new treatment options have long been needed for RAI-R patients with DTC who have a poor prognosis.

In recent years, research has been elucidating the aberrant metabolic pathways within cells that allow the development of cancers and identifying targeted therapies based on inhibition of these pathways. Since solid tumors require blood to supply the nutrients required for growth, one potential objective for targeted therapy is inhibition of angiogenesis. Agents that inhibit angiogenesis by interrupting signaling pathways, including tyrosine kinase inhibitors (TKIs), are currently being investigated for treatment of RAI-R DTC. Sorafenib, an orally active agent that targets various tyrosine and RAF (serine/threonine) kinases in tumor cells and tumor vasculature, is currently indicated for the treatment of advanced hepatocellular carcinoma and renal cell carcinoma. Sorafenib is recently approved to treat late-stage (metastatic) differentiated thyroid cancer. A number of other TKIs are in the pipeline, in Phase 2 or early Phase 3 trials.

Physicians need to be thoroughly familiar with the molecular targets and the efficacy and safety profiles of these various agents to assess the patient's suitability for treatment, customize the treatment choice, monitor appropriately, and manage AEs as they occur to optimize outcomes, maintain patient compliance to the treatment regimen, and avoid potentially life-threatening consequences. The aim of this monograph is to educate physicians who have had limited experience with these agents about their efficacy and safety.


Patient outcomes could be measurably improved if physicians were better able to...

  1. Discuss the role of VEGFR tyrosine kinase activity and cross-signaling between multiple kinase pathways in thyroid tumorigenesis, progression, and metastasis
  2. Identify the significance of genetic alterations in the pathogenesis of advanced differentiated thyroid cancer
  3. Associate the most predominant RAF signal kinase with its potent role in MAPK pathway signaling
  4. Review the fundamental role that signaling gene mutations may play in thyroid tumorigenesis
  5. Evaluate the effectiveness of targeted therapies that inhibit pathways constitutively activated during early stages of tumor development


This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Dannemiller and CogniMed Inc. Dannemiller is accredited by the ACCME to provide continuing medical education for physicians. Dannemiller designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity. Statements of Credit will be provided by web-certification or mail following activity participation and upon completion and return of the evaluation form to CogniMed Inc. via submission at the end of the activity; by mail to CogniMed Inc., 70 South Orange Avenue, Suite 230, Livingston, NJ 07039; or by fax to 973-758-0052. Please allow 4 to 6 weeks for the delivery of your statement. If you have any questions about your certificate, please e-mail


In accordance with the Accreditation Council for Continuing Medical Education (ACCME), Dannemiller requires that any person who is in a position to control the content of a CME activity must disclose all relevant financial relationships they have with a commercial interest."

This educational activity may contain discussion of unpublished and/or investigational uses of agents that are not indicated by the FDA. The faculty have been asked to disclose this information when presented. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings. Further, attendees/participants should appraise the information presented critically and are encouraged to consult appropriate resources for any product or device mentioned in this program.

To resolve identified/potential conflicts of interest, the educational content was fully reviewed by a physician member of the Dannemiller Clinical Content Review Committee who have no financial relationships with commercial interests. The resulting certified activity was found to provide educational content that is current, evidence based and commercially balanced.


It is the policy of Dannemiller to ensure fair balance, independence, objectivity, and scientific rigor in all programming. All faculty and planners participating in sponsored programs are expected to identify and reference off-label product use and disclose any significant relationships with those supporting the activity or any others whose products or services are discussed. The faculty for this activity have disclosed that there will be discussion about the use of products for nonFDA-approved indications. In accordance with the Accreditation Council for Continuing Medical Education standards, parallel documents from other accrediting bodies, and Dannemiller policy, the following disclosures have been made:

Mark T. Nadeau, MD, MBA, FAAFP, Clinical Content Reviewer, has nothing to disclose.
Gordon Ringler, Project Manager, has nothing to disclose.

CogniMed Inc.
Estelle Perera, Senior Director, Scientific Affairs and Program Design, and Medical Writer, has nothing to disclose.

Curlyn Larmony, Associate Program Manager, has nothing to disclose.

Steven I. Sherman, MD, serves on the speaker programs of Onyx Pharmaceuticals and is a consultant on the advisory board for Bayer HealthCare Pharmaceuticals.

Lori Wirth, MD, is a consultant on the advisory board for Amgen Inc; Exelixis, Inc; and Novartis and serves as an investigator for AstraZeneca and Eisai, Inc.

The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of CogniMed Inc. or Dannemiller, Onyx Pharmaceuticals or Bayer HealthCare Pharmaceuticals. This material is prepared based upon a review of multiple sources of information, but it is not exhaustive on the subject matter. Therefore, healthcare professionals and other individuals should review and consider other publications and materials on the subject matter before relying solely on the information contained within this educational activity.

The ideas and opinions presented in this educational activity are those of the faculty and do not necessarily reflect the views of Dannemiller and/or its agents. As in all educational activities, we encourage the practitioners to use their own judgment in treating and addressing the needs of each individual patient, taking into account that patient's unique clinical situation. Dannemiller disclaims all liability and cannot be held responsible for any problems that may arise from participating in this activity or following treatment recommendations presented. Jointly sponsored by CogniMed Inc and Dannemiller.

This activity is supported by an independent educational grant provided by Onyx Pharmaceuticals, Inc. and Bayer HealthCare LLC.