Bladder cancer: treatment after progression. Results of the second retrospective analysis of data on the efficacy of vinflunin in patients with metastatic urothelial cancer in real clinical practice in Russia

Objective. There is the second generalized analysis of administration of vinflunine in real clinical practice in Russia.
Materials and methods. This analysis gathered 15 patients with urothelial carcinoma treated using this medicine in 8 cancer centers in Russia. We assessed efficacy, safety profile of vinflunine in this subset of patients.
Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 73.3 %, one patient demonstrated complete response. Median of response duration accounts for 3.8 months. Six-month and 1-year survival rate made up 93.3 %. Adverse events were observed in 53.5 %, with only one episode of neutropenia 4 grade.
Conclusion. In our second analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, we confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

1. Witjes J.A., Comperat E., Cowan N.C. et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014;65 (4):778-92. DOI: 10.1016/j.eururo.2013.11.046.

2. Williams S.B., Shan Y., Ray-Zack M.D. et al. Comparison of costs of radical cystectomy vs trimodal therapy for patients with localized muscle-invasive bladder cancer. JAMA Surg 2019;154(8):e191629. DOI: 10.1001/jamasurg.2019.1629.

3. Winquist E., Kirchner T.S., Segal R. et al. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004;171(2 Pt 1):561-9. DOI: 10.1097/01.ju.0000090967.08622.33.

4. Apolo A.B., Vogelzang N.J., Theodorescu D. New and promising strategies in the management of bladder cancer. Am Soc Clin Oncol Educ Book 2015;35:105-12. DOI: 10.14694/EdBook_AM.2015.35.105.

5. Korkes F., Palou J. High mortality rates after radical cystectomy: we must have acceptable protocols and consider the rationale of cutaneous ureterostomy for high-risk patients. Int Braz J Urol 2019;45(6):1090-3. DOI: 10.1590/S1677-5538.IBJU.2019.05.03.

6. Klapheke A., Yap S.A., Pan K., Cress R.D. Sociodemographic disparities in chemotherapy treatment and impact on survival among patients with metastatic bladder cancer. Urol Oncol 2018;36 (6):308.e19-25. DOI: 10.1016/j.urolonc.2018.03.008.

7. DelFattore J. Death by Stereotype? Cancer treatment in unmarried patients. N Engl J Med 2019; 381(10):982-5. DOI: 10.1056/NEJMms1902657.

8. Merck KGaA. US FDA breakthrough therapy designation and submission of application for Bavencio for first-line maintenance treatment of locally advanced or metastatic urothelial carcinoma. [Press release] April 9, 2020.

9. Kapetanakis V., Prawitz T., Schlichting M. et al. Comparing progression-free survival (PFS) in second-line (2L) urothelial carcinoma (UC) treatments from single-arm trials: Importance of using appropriate methods. J Clin Oncol 2020;38(Suppl 6):573.

10. Baldini C., Champiat S., Vuagnat P., Massard C. Durvalumab for the management of urothelial carcinoma: a short review on the emerging data and therapeutic potential. Onco Targets Ther 2019;12:2505-12. DOI: 10.2147/OTT.S141040.

11. Teo M.Y., Seier K., Ostrovnaya I. et al. Alterations in DNA damage response and repair genes as potential marker of clinical benefit from PD-1/PD-L1 blockade in advanced urothelial cancers. J Clin Oncol 2018;36(17):1685-94. DOI: 10.1200/JCO.2017.75.7740.

12. Powles T., Duran I., van der Heijden M.S. et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2018;391(10122):748-57. DOI: 10.1016/S0140-6736(17)33297-X.

13. Rosenberg J.E., O'Donnell P.H., Balar A.V. et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol 2019;37(29):2592-600. DOI: 10.1200/JCO.19.01140.

14. Loriot Y., Necchi A., Park S. et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med 2019;381(4):338-48. DOI: 10.1056/NEJMoa1817323.

15. Powles T. 2020 American Society of Clinical Oncology annual meeting: Abstract LBA1. Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line (1L) chemotherapy in advanced urothelial carcinoma (UC): JAVELIN Bladder 100 phase III interim analysis. Available at: https://meeting-library.asco.org/record/186872/slide.

16. Volkova M.I., Chernyaev V.A., Matveev V.B. et al. Vinflunine as second-line therapy for advanced urothelial carcinoma: Russian observational study Onkourologiya = Cancer Urology 2017; 13(3):110-8. (In Russ.).

17. Van Persijn van Meerten E.L., Gelderblom H., Bloem J.L. RECIST revised: implications for the radiologist. A review article on the modi ed RECIST guideline. Eur Radiol 2010;20 (6):1456-67. DOI: 10.1007/s00330-009-1685-y.

18. Bellmunt J., Theodore C., Demkov T. et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009;27(27):4454-61. DOI: 10.1200/JCO.2008.20.5534.

19. Medioni J., Di Palma M., Guillot A. et al. Efficacy and safety of Vinflunine for advanced or metastatic urothelial carcinoma in routine practice based on the French multi-centre CURVE study. BMC Cancer 2016;16(1):217. DOI: 10.1186/s12885-016-2262-9.

20. Pistamaltzian N., Tzannis K., Pissanidou V. et al. Treatment of relapsed urothelial bladder cancer with vinflunine: real-world evidence by the Hellenic Genitourinary Cancer Group. Anticancer Drugs 2016;27(1):48-53. DOI: 10.1097/CAD.0000000000000297.

21. Holmsten K., Dohn L., Jensen N.V. et al. Vinflunine treatment in patients with metastatic urothelial cancer: a Nordic retrospective multicenter analysis. Oncol Lett 2016;12(2):1293-300. DOI: 10.3892/ol.2016.4775.

22. Hussain S.A. ESMO 2016:abstract #800P and poster.

23. Passalacqua R. ASCO 2016: abstract #e16031.

24. Castellano D., Puente J., de Velasco G. et al. Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract after failure of one platinum-based systemic therapy in clinical practice. BMC Cancer 2014;14:779. DOI: 10.1186/1471-2407-14-779.

25. Culine S., Theodore C., De Santis M. et al. A phase II study of vinflunine in bladder cancer patients progressing after first-line platinum-containing regimen. Br J Cancer 2006;94(10):1395-401. DOI: 10.1038/sj.bjc.6603118.

26. Vaughn D.J., Srinivas S., Stadler W.M. et al. Vinflunine in platinum-pretreated patients with locally advanced or metastatic urothelial carcinoma: results of a large phase 2 study. Cancer 2009;115 (18):4110-7. DOI: 10.1002/cncr.24460.

27. Retz M., de Geeter P., Goebell P.J. et al. Vinflunine in routine clinical practice for the treatment of advanced or metastatic urothelial cell carcinoma - data from a prospective, multicenter experience. BMC Cancer 2015;15:455. DOI: 10.1186/s12885-015-1434-3.