Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis. Issue 2 (11th April 2021)

• Record Type: Journal Article
• Authors: Efstathiadou, Zoe A.; Tsentidis, Charalambos; Bargiota, Alexandra; Daraki, Vasiliki; Kotsa, Kalliopi; Ntali, Georgia; Papanastasiou, Labrini; Tigas, Stelios; Toulis, Konstantinos; Pazaitou-Panayiotou, Kalliopi; Alevizaki, Maria
• Is Part Of: European thyroid journal. Volume 10:Issue 2(2021)
• Page Start: 125
• Page End: 139
• Publication Date: 2021-04-11
• Subjects: Tyrosine kinase inhibitors -- Medullary thyroid cancer -- Tyrosine kinase; Thyroid gland -- Diseases -- Periodicals; Thyroid Diseases -- Periodicals; 612.44
• DOI: 10.1159/000509457
• Languages: English
• ISSNs: 2235-0640

Abstract

Abstract : Introduction: Tyrosine kinase inhibitors (TKIs) have been used in patients with advanced medullary thyroid carcinoma (MTC); however, data on their effectiveness and safety are limited. The aim of this systematic review and meta-analysis was to document clinical response and toxicities of TKIs in advanced MTC. Methods: We systematically searched major databases for articles or abstracts on TKI use in MTC patients until May 2018. Objective response (OR), defined as the sum of complete + partial response, expressed as percentage, was our primary endpoint, while disease stability, disease progression (DP), median progression-free survival (PFS), and drug discontinuation rate due to adverse events (AEs) were secondary endpoints. Pooled percentages, PFS time, and 95% CIs were reported. Results: Thirty-three publications were finally included in the analysis: 1 phase IV, 2 phase III trials evaluating vandetanib and cabozantinib, respectively, 20 phase I or II studies, and the remaining 10 studies of retrospective-observational nature. OR was documented in 28.6% (95% CI 25.9–31.9) of patients. Stable disease was recorded in 46.2% (95% CI 43.3–49.1). Overall, DP was observed in 22.9% (95% CI 20.4–27.6). Grade 3 or more AEs occurred in 48.5% (95% CI 45.5–51.5) of patients, and drug discontinuation was reported in 44.7% (95% CI 41.7–47.6). In general, use of TKIs conferred a PFS of 23.3 months (95% CI 21.07–25.5). In particular, vandetanib induced an OR in 33.8% (95% CI 29.6–38.0) of patients and cabozantinib in 27.7% (95% CI 22.05–33.4). DP occurred in 23.7% (95% CI 19.9–27.6) with vandetanib use and in 22.6% (95% CI 17.4–27.9) in cabozantinib-treated patients. Sorafenib, the third most frequently studied drug, showed intermediate efficacy, but higher discontinuation rates. Conclusion: Treatment with TKIs in MTC patients with progressive disease is associated with a moderate therapeutic benefit, with achievement of either disease stability or partial response in 73%. The toxicity of these drugs is not negligible, but it is, nonetheless, manageable.