Predictive factors of short and long-term vandetanib response in locally advanced or metastatic medullary thyroid cancer: a single center experience

Objectives: Vandetanib (V) is an important drug in the metastatic medullary thyroid cancer (MTC) treatment. The objective of this study was to evaluate the presence of predictors of V response, in short and long period, in locally advanced or metastatic MTC patients (pts). Methods: Seventy-nine locally advanced or metastatic MTC pts with progressive or symptomatic disease, referred to our Center between 2007 and 2018 and already treated surgically and with other systemic therapies, were treated with V. During follow-up it was performed clinical examination, biochemical and morphological evaluation. Twenty-five pts were treated with V for less than 12 months (short responders, Group 1), 54 patients were treated with V for at least 12 months (long responders, Group 2). Results: The genetic screening showed that in the Group 1, 4/25 (16%) pts were inherited forms and 21/25 (84%) pts were sporadic cases. In the Group 2, 8/54 (14.8%) pts were inherited forms and 46/54 (85.2%) pts were sporadic cases. The evaluation of somatic mutations showed that RET mutation was present in 82.3% and in 95.3% of pts in Group 1 and in Group 2, respectively. However, the presence of RET mutations, it wasn’t a predictor of response to treatment. The metastases site wasn’t correlated with the outcome. Otherwise, we observed that in long responders group, 47/54 (87%) pts showed at least one adverse events (AE) during V treatment with a correlation between AE and V response (P=0.02). In this group we also observed a statistically significant correlation between the younger age (<45 yrs) at screening and a greater response to V (P=0.01) and between the absence of progression disease at screening and response to V (P<0.0001). In the long term outcome, considering the last CT scan performed at the data cut-off during the treatment, 29/54 (53.7%) pts showed a persistent response to V after a median follow-up of 41 months. Moreover, we observed that the pts in the Group1 had a more aggressive disease and a more advanced age at screening than pts in Group 2. The estimated median Progression Free-Survival of all patients was 47 months. Conclusions: In our study, it was observed that the appearance of AE during V treatment, the younger age and the absence of progression disease at screening were predictive factors of long-term response to V in MTC pts. Moreover, RET somatic mutations were very frequent in the metastatic MTC patients but it wasn’t a predictor of response to V.