Impact of using novel antitumor drugs in adult patients with locally advanced or metastatic urothelial carcinoma on reducing cancer mortality in Russia

Background. Standard first-line therapy options for patients with locally advanced or metastatic urothelial carcinoma (UC) is platinum-based chemotherapy. Currently,  patients  also have access to immune checkpoint inhibitors (ICIs) such as pembrolizumab, nivolumab, and atezolizumab, along with avelumab, which, unlike other drugs in this class, can be used as maintenance therapy after first-line platinum-based chemotherapy.

Aim. To evaluate the effects of using ICIs in treating adult patients with locally advanced or metastatic UC on reducing overall and one-year cancer mortality in Russia.

Materials and methods.  A mathematical model based on overall survival and progression-free survival data from clinical trials has been proposed. This model describes duration of therapy and treatment outcomes for cases of treatment without ICIs (routine clinical practice); with pembrolizumab, nivolumab, and atezolizumab in first and second-line therapy according to real-life clinical practice (current practice); and with avelumab as maintenance  therapy after platinum-based chemotherapy (proposed practice) over a 3-year period. The model was used to estimate the number of lives saved and healthcare system costs when transitioning from historical to current practice, and from current to proposed practice over a three-year horizon, considering the number of locally advanced or metastatic UC patients who may start platinum-based therapy annually in Russia.

Results. Annually, up to 4,182 patients with locally advanced or metastatic UC in Russia can start platinum-based chemotherapy. Compared to  historical  practice, the  use of pembrolizumab, nivolumab, and atezolizumab in the  first and second lines of therapy in accordance with the routine clinical practice allows to reduce mortality from malignant neoplasms by 553 cases over a 3-year horizon. Over the same period, avelumab-based treatment  would additionally save 2,506 lives. Moreover, the cost of saving one life with the use of avelumab amounts to 6.0 million rubles, which is 9 % lower than the cost of saving one life with the use of other ICIs (6.6 million rubles).

Conclusion. The use of avelumab as maintenance therapy after platinum-based chemotherapy in the 1^st line in patients with locally advanced or metastatic UC has a significant and quantifiable impact on reducing cancer-related mortality in Russia.

1. Resolution of the Government of the Russian Federation No. 512 dated 31.03.2021 “Amendments to the State Program of the Russian Federation “Development of healthcare”. (In Russ.).

2. Sridhar S.S., Powles T., Gupta S. et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma: long-term follow-up from the JAVELIN Bladder 100 trial in subgroups defined by 1L chemotherapy regimen and analysis of overall survival from start of 1L chemothe, rapy. 2023 ASCO Genitourinary Cancers Symposium (February 16–18, 2023). San Francisco, CA, 2023, 21 p.

3. Balar A.V., Castellano D.E., Grivas P. et al. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann Oncol 2023;34(3):289–99. DOI: 10.1016/elsevier_cm_policy

4. Van der Heijden M.S., Loriot Y., Durán I. et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma: a long-term overall survival and safety update from the phase 3 IMvigor211 clinical trial. Eur Urol 2021;80(1):7–11.

5. Kotenko D.V. The use of cancer immunology drugs as mono- and combined therapy for locally advanced and metastatic bladder cancer (a review of clinical trials). Onkologiya. Zhurnal imeni P.A. Gertsena = P.A. Herzen Journal of Oncology 2019;8(6):466–70. (In Russ.).

6. State of oncological care in Russia in 2021. Eds.: А.D. Kaprin, V.V. Starinskiy, A.O. Shachzadova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMITS radiologii” Minzdrava Rossii, 2022. 239 p. (In Russ.).

7. Clinical Guidelines. Bladder cancer, 2020. Available at: https://cr. minzdrav.gov.ru/recomend/11_2 (accessed on 20.05.2023). (In Russ.).

8. Startsev V.Yu., Balashov A.E., Merzlyakov A.S. et al. Molecular determinants of recurrences of the human urothelial tumor. Onkourologiya = Cancer Urology 2021;17(3):130–9. (In Russ.). DOI: 10.17650/1726-9776-2021-17-3-130-139

9. Kalpinsky A.S. Bladder cancer: immunotherapy for all? Available at: https://roou.ru/blog/rmp-immunoterapiya-dlya-vseh/ (accessed on 20.05.2021). (In Russ.).

10. David K.A., Milowsky M.I., Ritchey J. et al. Low incidence of perioperative chemotherapy for stage III bladder cancer 1998 to 2003: a report from the National Cancer Data Base. J Urol 2007;178(2):451–4.

11. Balar A.V., Galsky M.D., Rosenberg J.E. et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 2017;389(10064):67–76.

12. Sharma P., Retz M., Siefker-Radtke A. et al. Nivolumab in meta-static urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol 2017;18(3): 312–22. DOI: 10.1016/S1470-2045(17)30065-7

13. Galsky M.D., Arranz Arija J.Á., Bamias A. et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 2020;395(10236):1547–57. DOI: 10.1016/S0140-6736(20)30230-0

14. Von der Maase H., Sengelov L., Roberts J.T. et al. Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 2005;23(21):4602–8.

15. De Santis M., Bellmunt J., Mead G. et al. Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/ carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986. J Clin Oncol 2012;30(2):191.

16. Powles T., Park S.H., Caserta C. et al. Avelumab first-line maintenance for advanced urothelial carcinoma: results from the JAVELIN Bladder 100 Trial After ≥2 years of follow-up. J Clin Oncol 2023;41(19):3486–92. DOI: 10.1200/JCO.22.01792

17. Galsky M.D., Saci A., Szabo P.M. et al. Nivolumab in patients with advanced platinum-resistant urothelial carcinoma: efficacy, safety, and biomarker analyses with extended follow-up from CheckMate 275. Clin Cancer Res 2020;26(19):5120–8. DOI: 10.1158/1078-0432.CCR-19-4162

18. Avksentyev N.A., Sisigina N.N., Frolov M.Yu., Makarov A.S. Analysis impact of using novel antineoplastic drugs on cancer mortality in Russia. Voprosy onkologii = Problems in Oncology 2021;67(6):768–76. (In Russ.).

19. Avxentyev N.A., Makarov A.S., Sisigina N.N. Impact assessment of expanding the utilization of novel antineoplastic drugs for lung cancer treatment on key performance indicators of the Federal project ”Cancer control”. Voprosy onkologii = Problems in Oncology 2023;69(2):538–48. (In Russ.). DOI: 10.37469/0507-3758-2023-69-3-538-548

20. Tsimafeyeu I.V., Alekseeva G.N., Petkau V.V. et al. Survival of patients with metastatic bladder cancer in the Russian Federation: results of a multicenter registry study URRU. Onkourologiya = Cancer Urology 2021;17(3):102–9. (In Russ.). DOI: 10.17650/1726-9776-2021-17-3-102-109

21. Ishhenko K.B. Epidemiology, clinical picture and diagnosis of urothelial tumors of the renal pelvis and ureter: current state of the problem. Zlokachestvennye opuholi = Malignant Tumours 2016;2(18):66–71. (In Russ.). DOI: 10.18027/2224-5057-2016-2-66-71