Viktoria Florentine Koehler1,2, Elke Berg1, Pia Adam3, Gian-Luca Weber4, Andreas Pfestroff4, Markus Luster4, Jana Maria Kutsch5, Constantin Lapa5, Benjamin Sandner6, Nada Rayes7, Carmina Teresa Fuss3, Michael C Kreissl8, Eva Hoster9, Stephanie Allelein10, Matthias Schott10, Andrei Todica11, Martin Fassnacht3, Matthias Kroiss1,3,12, Christine Spitzweg1,13. 1. Department of Internal Medicine IV and University Hospital, LMU Munich, Munich, Germany. 2. Department of Internal Medicine I, Goethe University Hospital, Frankfurt, Germany. 3. Division of Endocrinology/Diabetology, Department of Internal Medicine I, University of Würzburg, Würzburg, Germany. 4. Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany. 5. Nuclear Medicine, Medical Faculty, University of Augsburg, Augsburg, Germany. 6. Department of Endocrinology, Nephrology and Rheumatology and Transplant-, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany. 7. Department of Visceral-, Transplant-, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany. 8. Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany. 9. Institute for Medical Information Processing, Biometry and Epidemiology, LMU Munich, Munich, Germany. 10. Division for Specific Endocrinology, Medical Faculty, University of Düsseldorf, Düsseldorf, Germany. 11. Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Germany. 12. Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. 13. Adjunct Academic Appointment, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA.
Abstract
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 (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one 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 by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The 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. The median OS for first-line treatment 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 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.
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 (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one 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 by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The 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. The median OS for first-line treatment 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 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.