Predictors Of Vandetanib Response In The Locally Advanced Or Metastatic Medullary Thyroid Cancer: A Single Center Experience

Objectives: Vandetanib (V) is a new option in the metastatic medullary thyroid cancer (MTC) treatment. In this study it was evaluated the presence of epidemiological, clinical and genetic predictors of V response in locally advanced or metastatic MTC patients (pts) treated for at least 12 months. Methods: Forty-five locally advanced or metastatic MTC pts with pro- gression or symptomatic disease, referred to our Center and already treated surgically and with other systemic therapies, were treated with V. During fol- low-up it was performed clinical examination, biochemical and morphological evaluation. All pts have taken V for at least 12 months. Results: The genetic screening showed that 7/45 (15.6%) pts were inher- ited forms and 38/45 (84.4%) were sporadic cases. The evaluation of somatic mutations were performed in 36/38 (94.7%) pts and it was observed that 34/36 (94.4%) were carriers of a hereditary or somatic genetic mutation. However, the presence of RET mutations, it wasn’t a predictor of response to treatment. All three pts with V804M RET mutation, that was demonstrated to confer resistance to V in ‘in vitro’ studies, responded to treatment. In our study group, the metastases site wasn’t correlated with the outcome. In 36/45 (80%) pts it was observed the presence of adverse events (AE) with a correlation between AE, particularly cutaneous rash, and V response (p = 0.01). A long-term out- come showed a morphologic and biochemical response in 39/45 (86.7%) pts. The Progression Free-Survival was 85% after six months. Conclusion: It was observed that the presence of AE was the only predic- tor of response to V treatment. Moreover, RET somatic mutations were very frequent in the metastatic MTC patients and also patients with ‘resistant muta- tions’ responded to treatment