Abstract
Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points. The terms "medullary thyroid" and "protein kinase inhibitor" (then including all TKIs) were searched in PubMed, ClinicalTrials.gov, and CENTRAL. Only original studies reporting the use of Vandetanib as single agent in MTC were included. The last search was performed on October 31, 2017 and registered in PROSPERO on December 12, 2017 (n = CRD42017081537). The search revealed 487 articles, and, after removing duplicates, reading title and abstract, and screening the eligible papers, 10 studied were finally included. Two papers were randomized controlled trials and eight were observational longitudinal studies. No data were available for overall survival. No heterogeneity nor publication bias were recorded in the pooled rate of complete response (0.7%) and stable disease (47%). Mild to moderate heterogeneity were recorded in the pooled rate of other endpoints. Data of the studies did not allow to perform a meta-analysis of time-to-event outcomes. Vandetanib should be considered as a promising treatment in advanced MTC. However, data based on RECIST endpoints do not currently provide high-level evidence on its efficacy.
Highlights
RationaleMedullary thyroid carcinoma (MTC) is a thyroid tumor which can occur as hereditary (20% of cases), due to an activating germline mutation of the REarranged during Transfection (RET) protooncogene, or sporadic (80%), with a somatic RET mutation [1]
This study demonstrates that a negligible rate of patients with advanced medullary thyroid cancer (MTC) treated by Vandetanib has a CR at the end of the study and less than a half has SD
Higher PFS was reported among Vandetanib- and Cabozantinibtreated patients with respect to controls (HR = 0.36; 95% CI, 0.22–0.58) [22]
Summary
RationaleMedullary thyroid carcinoma (MTC) is a thyroid tumor which can occur as hereditary (20% of cases), due to an activating germline mutation of the REarranged during Transfection (RET) protooncogene, or sporadic (80%), with a somatic RET mutation [1]. While the majority of these carcinomas involves only the thyroid gland and reaches the complete cure following total thyroidectomy, a not negligible rate manifests as locally advanced and/or with distant metastases. The latter patients have a poor prognosis and need alternative treatments other than surgery. Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Methods: The terms “medullary thyroid” and “protein kinase inhibitor” ( including all TKIs) were searched in PubMed, ClinicalTrials.gov, and CENTRAL. The last search was performed on October 31, 2017 and registered in PROSPERO on December 12, 2017 (n = CRD42017081537)
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