Analysis of treatment outcomes in patients with progressive locally advanced non-resectable and disseminated medullary thyroid cancer receiving vandetanib outside of clinical trials (Russian experience)

The study objective is to perform retrospective analysis of the efficacy and safety of vandetanib for metastatic and non-resectable medullary thyroid cancer in routine clinical practice.
Materials and methods. We analyzed treatment outcomes in 46 patients treated with vandetanib. We also evaluated progression-free survival, overall survival, time to progression, and frequency of adverse events.
Results. At a median follow-up time of 27.4 months (range: 2.5–106.5 months) and median duration of vandetanib therapy of 21 months, disease progression was registered in 32.6 % of cases, whereas stable disease was observed in 28.3 % of cases and 8.7 % of study participants demonstrated partial response. One patient had complete response to treatment. Almost one-third of patients (28.2 %) died, including 2 individuals whose death was not associated with cancer. The one-year and three-year progression-free survival rates were 67.3 % and 33.3 %, respectively; the two-year and five-year overall survival rates were 82.4 % and 29.4 %, respectively. The efficacy of therapy was confirmed by a 79.4 % decrease in the serum level of calcitonin after treatment initiation. Side effects were observed in 33.9 % of patients (primarily skin and gastrointestinal toxic reactions) and were easily managed in most of the cases. Eight individuals (17.4 %) required cessation of vandetanib due to adverse events.
Conclusion. Our findings suggest high efficacy and acceptable safety profile of vandetanib in the treatment of progressive locally advanced non-resectable and disseminated medullary thyroid cancer

1. Злокачественные новообразования в России в 2018 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена, 2019. 250 с. Доступно по: http://www.glavonco.ru/cancer_register/Забол_2018_Электр.pdf. [Malignant tumors in Russia in 2018 (morbidity and mortality). Ed by A.D. Kaprin, V.V. Starinsky, G.V. Petrova. Moscow: MNIOI im. P.A. Gertzena, 2019. 250 p. Available at: http://www.glavonco.ru/cancer_register/Забол_2018_Электр.pdf. (In Russ.)].

2. Howlader N., Noone A.M., Krapcho M. et al. SEER Cancer Statistics Review, 1975-2017, National Cancer Institute. Available at: https://seer.cancer.gov/csr/1975_2017.

3. Wells S.A. Jr, Asa S.L., Dralle H. et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25(6):567–610. DOI: 10.1089/thy.2014.0335.

4. Sippel R.S., Kunnimalaiyaan M., Chen H. Current management of medullary thyroid cancer. Oncologist 2008;13(5):539–47. DOI: 10.1634/theoncologist.2007-0239.

5. Румянцев П.О., Ильин А.А., Саенко В.А. и др. Рак щитовидной железы: современные подходы к диагностике и лечению. М.: ГЭОТАРмедиа, 2009. 448 с. [Rumyantsev P.O., Ilyin A.A., Saenko V.A. Thyroid cancer: modern approaches to diagnosis and treatment. Moscow: Geotar-media, 2009. 448 p. (In Russ.)].

6. Saad M.F., Ordonez N.G., Rashid R.K. et al. Medullary carcinoma of the thyroid. A study of the clinical features and prognostic factors in 161 patients. Medicine (Baltimore) 1984;63(6):319–42.

7. Vitale G., Tagliaferri P., Caraglia M. et al. Slow release lanreotide in combination with interferon-alpha2b in the treatment of symptomatic advanced medullary thyroid carcinoma. J Clin Endocrinol Metab 2000;85(3):983–8. DOI: 10.1210/jcem.85.3.6435.

8. Hundahl S.A., Fleming I.D., Fremgen A.M., Menck H.R. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995 [see comments]. Cancer 1998;83(12):2638–48.

9. Roman S., Lin R., Sosa J.A. Prognosis of medullary thyroid carcinoma: demographic, clinical, and pathologic predictors of survival in 1252 cases. Cancer 2006;107(9):2134–42. DOI: 10.1002/cncr.22244.

10. Wells S.A. Jr, Robinson B.G., Gagel R.F. et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30(2):134–41. DOI: 10.1200/JCO.2011.35.5040.

11. Fox E., Widemann B.C., Chuk M.K. et al. Vandetanib in children and adolescents with multiple endocrine neoplasia type 2B associated medullary thyroid carcinoma. Clin Cancer Res 2013;19(15):4239–48. DOI: 10.1158/1078-0432.CCR-13-0071.

12. Massicotte M.H., Brassard M., ClaudeDesroches M. et al. Tyrosine kinase inhibitor treatments in patients with metastatic thyroid carcinomas: a retrospective study of the TUTHYREF network. Eur J Endocrinol 2014;170(4):575–82. DOI: 10.1530/EJE-13-0825.

13. Chougnet C.N., Borget I., Leboulleux S. et al. Vandetanib for the treatment of advanced medullary thyroid cancer outside a clinical trial: results from a French cohort. Thyroid 2015;25(4):386–91. DOI: 10.1089/thy.2014.0361.

14. AstraZeneca to compare the effects of two doses of vandetanib in patients with advanced medullary thyroid cancer. Available from: http://www.clinicaltrials.gov/ct2/show/NCT01496313.

15. Капрелса. Инструкция по медицинскому применению лекарственного препарата. Доступно по: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=6dff8568-b758-469b-806a-a7309a0d98ef&t=. [Caprelsa. Instructions for medical use. Available by: http://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=6dff8568-b758-469b-806a-a7309a0d98ef&t=. (In Russ.)].

16. Каприн А.Д., Иванов С.А., Севрюков Ф.Е. и др. Эффективность дистанционной лучевой терапии и таргетной терапии вандетанибом нерезектабельного и прогрессирующего медуллярного рака щитовидной железы. Опухоли головы и шеи 2018;8(3):72–6. [Kaprin A.D., Ivanov S.A., Sevryukov F.E. et al. Efficacy of external beam radiotherapy and targeted therapy with vandenanib in patients with inoperable and progressive medullary thyroid cancer. Opukholi golovy i shei = Head and Neck Tumors 2018;8(3):72–6. DOI: 10.17650/2222-1468-2018-8-3-72-76. (In Russ.)].

17. Tappenden P., Carroll C., Hamilton J. et al. Cabozantinib and vandetanib for unresectable locally advanced or metastatic medullary thyroid cancer: a systematic review and economic model. Health Technol Assess 2019;23(8):1–144. DOI: 10.3310/hta23080.