Vandetanib and the predictive factors of durable response in locally advanced or metastatic medullary thyroid cancer: a single center experience.

Objectives: Vandetanib is an important target therapy in the advanced metastatic medullary thyroid cancer (MTC) treatment. The aim of this study was to evaluate the predictors of durable response to vandetanib in locally advanced or metastatic MTC patients (pts). Methods: Seventy-nine locally advanced or metastatic, progressive or symptomatic, MTC pts were treated with vandetanib in our center between 2007 and 2018. During follow-up, it was performed clinical, biochemical and morphological evaluation. Twenty-five pts were treated with the drug for < 12 months (Short Responders, SR) while 54 patients were treated for at least 12 months (Long Responders, LR). Results: The genetic screening showed that RET somatic mutation was present in 82.3% and in 95.3% of SR and LR patients, respectively but it wasn’t a predictor of response to vandetanib. Also the metastases site wasn’t correlated with the response to the drug. Regarding the other possible predictive factors of durable response, we observed that 87% of LR patients showed at least one adverse events (AE) with a correlation between the AE and the response to vandetanib (p = 0.02). Moreover, we observed that a younger age (<45 yrs) and the absence of progression disease at screening were correlated with a greater response to the drug (p = 0.01) and (p<0.0001), respectively. Finally, we observed that SR patients had a more aggressive disease and more advanced age at screening than LR patietns. Conclusions: The younger age, the absence of progression disease at screening and the appearance of AE during vandetanib treatment were the important predictive factors of durable response to the drug. Otherwise, RET somatic mutations were very frequent in our MTC patients but they did not correlate with the response to the drug.