ESMO E-Learning: New Systemic Treatment Options for Radioiodine-refractory Differentiated and Medullary Thyroid Cancers

Learning Objectives

  • To describe epidemiology, pathogenesis, differential diagnosis, natural course and outcome of patients with thyroid cancer
  • To evaluate recent clinical trials data focused on the efficacy and safety of new systemic treatment options for radioiodine-refractory differentiated and medullary thyroid cancers  
  • To help to employ best clinical practices regarding therapy selection to improve outcomes in patients with radioiodine-refractory differentiated and medullary thyroid cancers
Title Duration Content CME Points CME Test
New Systemic Treatment Options for Radioiodine-refractory Differentiated and Medullary Thyroid Cancers 36 min. 55 slides 1 Take Test
Schoffski Patrick
Patrick Schöffski
Read more

Thyroid cancer accounts for more than 90% of all endocrine malignancies and represents <1% of all human cancers. Often considered rare, however one in about 130 men and women will be diagnosed with thyroid cancer during their lifetime. Radiation exposure is the best known risk factor. In addition there is a genetic predisposition, in particular to differentiated thyroid cancer in Cowden, Gardner and FAP syndromes, and to medullary thyroid cancer in MEN 2A and 2B syndromes.

Molecular studies have identified a number of abnormalities in thyroid cancer associated with cell Transformation, progression and dedifferentiation. Distinct molecular events are linked with specific stages and phenotypes of thyroid cancer.

Natural course and outcome show variable presentation from clinically insignificant cases to very aggressive disease. Most of patients with differentiated thyroid carcinoma have excellent disease-specific survival, resulting in a low number of deaths as compared to other solid tumours. However, the majority of patients with poorly differentiated thyroid cancer or anaplastic thyroid carcinoma succumb to their disease despite aggressive treatment.

Differentiated thyroid carcinoma accounts for 90-95% of all cases of thyroid cancer and is highly curable. It includes the most common entities, papillary and Follicular carcinoma. Primary curative treatment involves surgery and radioactive iodine (RAI) therapy. The treatment is followed by life-long thyroxine administration. Despite low disease-specific mortality, global risk of recurrence is 20-30% over 30-40 years. Around 8% of patients with local relapse and 50% of patients with metastasis will die of thyroid cancer. RAI is the mainstay treatment in metastatic differentiated thyroid carcinoma.

Roughly 25% of RAI-treated patients become iodine-negative, in other words resistant, following repeated 131-I therapy. Some of these patients potentially qualify for best supportive care, tyrosine kinase inhibitors (TKI), chemotherapy, experimental therapy. Doxorubicin is the only FDA-approved chemotherapeutic option for patients with recurrent or refractory disease, with highly variable response rate, but it has never been studied in adequately powered randomized trials. Possible indications include inoperable, progressive, symptomatic disease, and TKI failure. Combination chemotherapy is not better than doxorubicin alone.

Differentiated thyroid carcinoma is becoming a role model for targeted therapy. Presence of constitutively activated tyrosine kinases makes it a logical candidate for targeted treatment. Oncogene addication and druggable molecular targets in thyroid cancer include B-RAF, cyclin D1, DNA-methylation, epigenetic alterations, growth factors, MET, p53, PI3K/Akt/PTEN, Ras, RET, VEGF, …

This E-learning module covers selected targeted agents, already approved or in advanced stages of clinical testing in thyroid cancer. The author summarizes that, for differentiated thyroid carcinoma, VEGFR TKI consistently show efficacy in RAI-refractory patients; responses are seen in all histological subtypes and molecular phenotypes; phase III data show improved progression-free survival (PFS) of sorafenib over placebo; no head-to-head comparison of VEGFR TKI has been performed; BRAF/MEK inhibition are currently evaluated in phase II studies; new strategies include combinations of different Antiangiogenic agents, VEGFRi/mTORi, Pi3K/MAP.

Medullary thyroid carcinoma is a distinct entity. Tyrosine kinase inhibitors targeting RET are effective and vandetanib showed improved PFS over placebo and has been approved in 2011; cabozantinib showed improved PFS over placebo and was approved by FDA in 2012; no head-to-head comparison is available or planned; tumours harboring M918T mutation appear to demonstrate the greatest benefit; and RET mutation alone can not explain all the efficacy observed. Few options for TKI-refractory patients exist and there is a limited trial activity in that setting.

This E-learning module covers novelties in systemic therapy for radioiodine-refractory differentiated and medullary thyroid cancers. It elaborates on the role and activity of various novel targeted agents and critically discusses on variable efficacy outcomes in clinical studies. The module serves as an excellent state of the art and CME opportunity in the field of systemic treatment for thyroid cancer.

Last update: 09 December 2013

The author has reported Cabozantinib/Exelixis research grant, speakers bureau, consulting function