Endocrine Abstracts

Targeted therapies have been used for about 10 years in patients with radioactive iodine refractory differentiated thyroid cancer (DTC) or metastatic medullary thyroid cancer (MTC). Decrease in tumor volume, improvement of symptoms, increase in progression free survivals have been observed with different drugs. So far, because of trial design and because of the long survival of patients with metastatic DTC or MTC, the benefit of these drugs on overall survival has not been demonstrated. The limits of the targeted therapies are related to their safety, their efficacy, and to the absence of predictive factors for treatment efficacy.

Toxicity include cardiovascular events (hypertension, ischemic events…), asthenia, cutaneous reaction (photosensitization, folliculitis, and in some cases squamous cell cancer), diarrhea, loss of weight, and renal toxicity. They have to be taken very seriously because they can be life threatening. They are responsible of dose regimen decrease in up to 50% of the patients and drug stop in up to 25% of the patients. Prevention and early treatment of these toxicities are therefore essential to keep patients on drug as long as possible.

Despite an astonishing efficacy, treatment responses remain however insufficient with no or very few complete response observed, so far, and a limited length of response The challenges we are facing include the understanding of the mechanisms of action of the drugs and of treatment failures and the determination of predictive factor for treatment response, including the finding of a biological significant target to choose specific targeted treatment. Drug titration should also allow a more appropriate dose regimen. In cases several drugs are available, we will need to compare treatment efficacy, treatment safety and determine the best treatment sequence. Combination of drugs is also a development to explore. Finally, a medico economic evaluation of these drugs will need to be performed. Saying so, it means that there is a long way forward to improve patient’s care.