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Koehler, Viktoria Florentine; Berg, Elke; Adam, Pia; Weber, Gian-Luca; Pfestroff, Andreas; Luster, Markus; Kutsch, Jana Maria; Lapa, Constantin; Sandner, Benjamin; Rayes, Nada; Fuss, Carmina Teresa; Kreissl, Michael; Hoster, Eva; Allelein, Stephanie; Schott, Matthias; Todica, Andrei; Fassnacht, Martin; Kroiss, Matthias and Spitzweg, Christine (2021): Real world efficacy and safety of multi-tyrosine kinase inhibitors in radioiodine refractory thyroid cancer. In: Thyroid

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BACKGROUND The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKI) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. PATIENTS AND METHODS We aimed to describe the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at 6 German referral centers. 101 patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated using the Kaplan-Meier method. RESULTS 97/101 patients had morphologically progressive disease before TKI initiation. Median PFS for first line treatment with sorafenib (n=33), lenvatinib (n=53) and pazopanib (n=15) was 9 (95% confidence interval, 5.2-12.8), 12 (4.4-19.6) and 12 months (4.4-19.6), respectively. Median OS in first line was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g. hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16/75 (21%) patients taking lenvatinib, in 3/42 (7%) patients taking sorafenib and in 3/24 (13%) patients taking pazopanib. CONCLUSION Sorafenib, lenvatinib and pazopanib are effective treatment options in the majority of RAI-refractory DTC patients. The PFS and 6-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favourably to sorafenib in the first line setting. However, more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era prior to TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

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