V804M RET MUTATION AND VANDETANIB RESPONSE IN METASTATIC MEDULLARY THYROID CANCER

Objective: Vandetanib is the most important treatment for metastatic medullary thyroid cancer (MTC). “In vitro” studies showed that the presence of the V804M RET mutation is associated with a selective resistance to vande- tanib. The objective of this study was to evaluate the response to vandetanib in metastatic V804M positive MTC patients. Methods: Four metastatic MTC patients, treated with vandetanib, were V804M RET positive. In 2 cases this mutation was a germinal mutation, while in other 2 was a somatic mutation. During the follow-up serum calcitonin lev- els and computed tomography scan were performed. Results: All cases had multiple metastatic lesions distributed in several organs. In 1 case (n 1) the enrollment was due to the symptom (diarrhea) while in 3 cases (n 2-3-4) to progression of the disease. The patient-1 had a symp- tomatic familial MTC. During the 55 months of follow up, she showed a stable disease (SD). The patient-2, 3 and 4 had a progressive metastatic sporadic MTC. During follow up, the patient-2 had an initial partial response (PR) and then a SD for 9 months, the patient-3 had an initial PR and then a SD for 14 months, the patient-4 did not respond to treatment. The most common adverse events were: acneiform rash in all patients, asthenia in patients 1 and 3, nau- sea, anorexia and weight loss in patient-2. Conclusions: In our study we observed that patients with „resistant“ mutations, such as V804M RET mutation, can respond (3/4) or not respond (1/4) to vandetanib. Therefore, also in the presence of this mutation it is indi- cated to start vandetanib since it can likely act also through mechanisms of action independently from RET inhibition such as VEGF-R inhibition.