Tyrosine Kinase Inhibitors (TKIs) have been used in patients with advanced Medullary Thyroid Carcinoma (MTC). However, for some compounds, data on 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: A literature search in MEDLINE, EMBASE and Cochrane until May 2018 was performed for articles or abstracts on TKI use in MTC. Studies were included in the meta-analysis if they presented results on tumor response to TKIs and/or adverse events of TKI therapy in 5 or more patients with MTC. The primary endpoint was objective response rate; disease stability, median progression free survival (PFS), drug discontinuation due to adverse events and Grade ≥3 adverse events (G3AEs) were secondary endpoints. Pooled percentages were calculated using meta-analysis of binomial data. Direct comparisons between specific drugs were not feasible and drug-specific effect estimates are provided descriptively.
Results: Thirty-three publications met the inclusion criteria for analysis: 1 phase IV trial, 2 phase III trials evaluating vandetanib and cabozatinib respectively, 20 phase I or II studies, with the remaining 10 studies of retrospective/observational nature. In total, data on 1274 patients were evaluated, 81 in phase IV trial, 561 in phase III trials, 441 in phase III trials and 191 in retrospective studies. Significant heterogeneity was detected for all effect estimates. Overall, objective response (CR & PR) was documented in 23% (95% CI 1728; I2=79.2%) of the patients, with higher rate observed with sunitinib [38% (95% CI 2059)]. Stable disease was reported in 44% (95% CI 3851; I2=71.1%) of patients, with higher rate observed with axitinib [58% (95% CI 3878)]. Overall disease progression was reported in 19% (95% CI 1425; I2=80.1%) of patients, with the lowest proportion reported in the motesanib [8% (95% CI 315)] patients. Overall, 33% (95% CI 2342; I2=90.7%) of patients discontinued the drug due to toxicity or disease progression with the lowest proportion reported in the cabozantinib group 14% (95% CI 1118). G3AEs were reported in 50% (95% CI 47.152.9) of patients, with the lowest proportion reported in pazopanib treated group [14.2% (95% CI 2.725.8)].
Conclusion: TKI treatment in MTC exhibited a significant benefit in terms of reducing progression of the disease, however, careful monitoring of patients on these drugs is important to manage AEs efficiently and proactively, and determine if the drug is no longer effective.
18 - 21 May 2019
European Society of Endocrinology