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Immunotherapy in urothelial cancer: recent data and perspectives

https://doi.org/10.17650/1726-9776-2017-13-4-16-24

Abstract

Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile  in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

About the Authors

M. I. Volkova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


Ya. V. Gridneva
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


A. S. Ol’shanskaya
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation
24 Kashirskoe Shosse, Moscow 115478


References

1. Состояние онкологической помощи населению России в 2016 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, 2017. 236 с. [State of oncological care in Russia in 2016. Eds.: A.D. Kaprin, V.V. Starinskiy, G.V. Petrova. Moscow: MNIOI im. P.A. Gertsena – filial FGBU “NMIRTS” Minzdrava Rossii, 2017. 236 p. (In Russ.)].

2. von der Maase H., Hansen S.W., Roberts J.T. et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18(17):3068–77. DOI: 10.1200/JCO.2000.18.17.3068. PMID: 11001674.

3. Sonpavde G., Sternberg C.N., Rosenberg J.E. et al. Second-line systemic therapy and emerging drugs for metastatic transitionalcell carcinoma of the urothelium. Lancet Oncol 2010;11(9):861–70. DOI: 10.1016/S1470-2045(10)70086-3. PMID: 20537950.

4. Bajorin D.F., Dodd P.M., Mazumdar M. et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999;17(10):3173–81. DOI: 10.1200/JCO.1999.17.10.3173. PMID: 10506615.

5. Bellmunt J., Théodore 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. PMID: 19687335.

6. Kandoth C., McLellan M.D., Vandin F. et al. Mutational landscape and significance across 12 major cancer types. Nature 2013;502(7471):333–9. DOI: 10.1038/nature12634. PMID: 24132290.

7. Inman B.A., Sebo T.J., Frigola X. et al. PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 2007;109(8):1499–505. DOI: 10.1002/cncr.22588. PMID: 17340590.

8. Gupta S., Gill D., Poole A., Agarwal N. Systemic immunotherapy for urothelial cancer: current trends and future directions. Cancers (Basel) 2017;9(2):15. DOI: 10.3390/cancers9020015. PMID: 28134806.

9. Merck Sharp & Dohme Corp; County Cork, Ireland: 2014. Pembrolizumab [package insert].

10. Plimack E.R., Bellmunt J., Gupta S. et al. Pembrolizumab (MK-3475) for advanced urothelial cancer: updated results and biomarker analysis from KEYNOTE-012. J Clin Oncol 2015;33(Suppl. S15):4502. DOI: 10.1200/jco.2015.33.15_suppl.4502.

11. Gupta S., O’Donnell P.H., Plimack E.R. et al. A phase 1b study of pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer; Proceedings of the 2015 AUA Annual Meeting; New Orleans, LA, USA. 15–19 May 2015; abstract MP68-11.

12. Bellmunt J., De Wit R., Vaughn D.J. et al. KEYNOTE-045: open-label, phase III study of pembrolizumab versus investigator’s choice of paclitaxel, docetaxel, or vinflunine for previously treated advanced urothelial cancer; Proceedings of the 2016 SITC Annual Meeting; National Harbor, MD, USA. 9–13 November 2016.

13. Bellmunt J., de Wit R., Vaughn D.J. et al. Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med 2017;376(11):1015–26. DOI: 10.1056/NEJMoa1613683. PMID: 28212060.

14. Powles T., Eder J.P., Fine G.D. et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014;515(7528): 558–62. DOI: 10.1038/nature13904. PMID: 25428503.

15. Loriot Y., Rosenberg J.E., Powles T.B. et al. Atezolizumab (atezo) in platinum (plat)-treated locally advanced/metastatic urothelial carcinoma (mUC): updated OS, safety and biomarkers from the Ph II IMvigor210 study. Ann Oncol 2016;27(6):266–95.

16. Powles T. IMvigor211: A phase III randomized study examining Atezolizumab versus chemotherapy for platinum-treated advanced urothelial carcinoma. Presented at the Second special conference of the European Association for Cancer Research (EACR), the American Association for Cancer Research (AACR) and the Italian Cancer Society (SIC), in Florence, Italy. June, 2017.

17. Massard C., Gordon M.S., Sharma S. et al. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol 2016;34(26):3119–25. DOI: 10.1200/JCO.2016.67.9761. PMID: 27269937.

18. Apolo A.B., Infante J.R., Hamid O. et al. Avelumab (MSB0010718C; anti-PD-L1) in patients with metastatic urothelial carcinoma from the JAVELIN solid tumor phase 1b trial: analysis of safety, clinical activity, and PD-L1 expression. J Clin Oncol 2016;34:4514.

19. Инструкция по медицинскому применению препарата ниволумаб (Опдиво) (ЛП-004026 от 22.12.2016). [Instructions for the medical use of the drug nivolumab (Opdivo) (LP-004026 dated December 22, 2016). (In Russ.)].

20. Sharma P., Bono P., Kim J.W. et al. Efficacy and safety of nivolumab monotherapy in metastatic urothelial cancer (mUC): results from the phase I/II CheckMate 032 study. J Clin Oncol 2016;34:4501.

21. Sharma P., Callahan M.K., Bono P. et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, twostage, multi-arm, phase 1/2 trial. Lancet Oncol 2016;17(11):1590–8. DOI: 10.1016/S1470-2045(16)30496-X. PMID: 27733243.

22. Sharma P., Retz M., Siefker-Radtke A. et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicenter, singlearm, phase 2 trial. Lancet Oncol 2017;18(3):312–22. DOI: 10.1016/S1470-2045(17)30065-7. PMID: 28131785.

23. Larkin J., Chiarion-Sileni V., Gonzalez R. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373(1):23–34. DOI: 10.1056/NEJMoa1504030. PMID: 26027431.

24. Carthon B.C., Wolchok J.D., Yuan J. et al. Preoperative ctla-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res 2010;16(10):2861–71. DOI: 10.1158/1078-0432.CCR-10-0569. PMID: 20460488.

25. Galsky M.D., Hahn N.M., Albany C. et al. Phase II trial of gemcitabine + cisplatin + ipilimumab in patients with metastatic urothelial cancer. J Clin Oncol 2016;34:abstract 357.

26. Balar A.V., Castellano D., O’Donnell P.H. et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol 2017;1470–2045(17):30616–2. DOI: 10.1016/S1470-2045(17)30616-2. PMID: 28967485.

27. Balar A.V., Galsky M.D., Loriot Y. et al. Atezolizumab (atezo) as first-line (1L) therapy in cisplatin-ineligible locally advanced/metastatic urothelial carcinoma (mUC): primary analysis of IMvigor210 cohort 1. J Clin Oncol 2016. Abstract LBA4500.


Review

For citations:


Volkova M.I., Gridneva Ya.V., Ol’shanskaya A.S. Immunotherapy in urothelial cancer: recent data and perspectives. Cancer Urology. 2017;13(4):16-24. (In Russ.) https://doi.org/10.17650/1726-9776-2017-13-4-16-24

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ISSN 1726-9776 (Print)
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