@article{3102631,
    title = "Benefits and Limitations of TKIs in Patients with Medullary Thyroid Cancer: A Systematic Review and Meta-Analysis",
    author = "Efstathiadou, Z.A. and Tsentidis, C. and Bargiota, A. and Daraki, V. and Kotsa, K. and Ntali, G. and Papanastasiou, L. and Tigas, S. and Toulis, K. and Pazaitou-Panayiotou, K. and Alevizaki, M.",
    journal = "European Thyroid Journal",
    year = "2021",
    volume = "10",
    number = "2",
    pages = "125-139",
    publisher = "S Karger AG",
    issn = "2235-0640, 2235-0802",
    doi = "10.1159/000509457",
    keywords = "afatinib;  aflibercept;  alectinib;  bevacizumab;  cabozantinib;  crizotinib;  cyclophosphamide;  doxorubicin;  gefitinib;  ibrutinib;  imatinib;  lapatinib;  larotrectinib;  nintedanib;  orantinib;  pazopanib;  protein tyrosine kinase inhibitor;  regorafenib;  sorafenib;  sunitinib;  tipifarnib;  vandetanib;  vatalanib, abdominal pain;  adult;  advanced cancer;  adverse drug reaction;  anorexia;  arthralgia;  asthenia;  cancer patient;  cancer staging;  cancer survival;  clinical trial;  constipation;  controlled study;  dysphonia;  dyspnea;  fatigue;  headache;  heart ventricle arrhythmia;  human;  hypertension;  kidney disease;  meta analysis;  mucosa inflammation;  musculoskeletal pain;  myalgia;  Newcastle-Ottawa scale;  outcome assessment;  perception deafness;  peripheral edema;  pregnancy outcome;  progression free survival;  quality control;  retrospective study;  Review;  systematic review;  thyroid cancer;  thyroid medullary carcinoma;  toxicity;  treatment response time;  vomiting",
    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. © 2020 The Author(s) Published by S. Karger AG, Basel."
}