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Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways

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Abstract

Purpose

Over the past 3 decades, no major treatment breakthrough has been reported for advanced bladder cancer. Recent Food and Drug Administration (FDA) approval of five immune checkpoint inhibitors in the management of advanced bladder cancer represent new therapeutic opportunities. This review examines the available data of the clinical trials leading to the approval of ICIs in the management of metastatic bladder cancer and the ongoing trials in advanced and localized settings.

Methods

A literature search was performed on PubMed and ClinicalTrials.gov combining the MeSH terms: ‘urothelial carcinoma’ OR ‘bladder cancer’, and ‘immunotherapy’ OR ‘CTLA-4’ OR ‘PD-1’ OR ‘PD-L1’ OR ‘atezolizumab’ OR ‘nivolumab’ OR ‘ipilimumab’ OR ‘pembrolizumab’ OR ‘avelumab’ OR ‘durvalumab’ OR ‘tremelimumab’. Prospectives studies evaluating anti-PD(L)1 and anti-CTLA-4 monoclonal antibodies were included.

Results

Evidence-data related to early phase and phase III trials evaluating the 5 ICIs in the advanced urothelial carcinoma are detailed in this review. Anti-tumour activity of the 5 ICIs supporting the FDA approval in the second-line setting are reported. The activity of PD(L)1 inhibitors in the first-line setting in cisplatin-ineligible patients are also presented. Ongoing trials in earlier disease-states including non-muscle-invasive and muscle-invasive bladder cancer are discussed.

Conclusions

Blocking the PD-1 negative immune receptor or its ligand, PD-L1, results in unprecedented rates of anti-tumour activity in patients with metastatic urothelial cancer. However, a large majority of patients do not respond to anti-PD(L)1 drugs monotherapy. Investigations exploring the potential value of predictive biomarkers, optimal combination and sequences are ongoing to improve such treatment strategies.

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Acknowledgements

Mathieu Rouanne is the recipient of a Scholarship Funding from the French Urological Association (Association Française d’Urologie)..

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Authors and Affiliations

  1. Department of Urology, Hôpital Foch, Université Versailles-Saint-Quentin-en-Yvelines, Université Paris-Saclay, 40 Rue Worth, 92150, Suresnes, France

    Mathieu Rouanne & Yann Neuzillet

  2. INSERM U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France

    Mathieu Rouanne

  3. Comité de Cancérologie de l’Association Française d’Urologie (ccAFU), Bladder Cancer Group, Maison de l’Urologie, Paris, France

    Mathieu Roumiguié, Nadine Houédé, Alexandra Masson-Lecomte, Pierre Colin, Géraldine Pignot, Stéphane Larré, Evanguelos Xylinas, Morgan Rouprêt & Yann Neuzillet

  4. Department of Urology, Institut Universitaire du Cancer, Oncopole, Toulouse, France

    Mathieu Roumiguié

  5. Department of Medical Oncology, CHU de Nîmes, Nimes, France

    Nadine Houédé

  6. INSERM U1194, Montpellier Cancer Research Institute, Université de Montpellier, Montpellier, France

    Nadine Houédé

  7. Department of Urology, Hôpital Saint-Louis, Université Paris-Diderot, Paris, France

    Alexandra Masson-Lecomte

  8. Department of Urology, Hôpital privé de la Louvière, Lille, France

    Pierre Colin

  9. Department of Urology, Institut Paoli-Calmettes, Marseille, France

    Géraldine Pignot

  10. Department of Urology, CHU de Reims, Reims, France

    Stéphane Larré

  11. Department of Urology, CHU Bichat, Paris, France

    Evanguelos Xylinas

  12. Department of Urology, Hôpital La Pitié-Salpétrière, AP-HP, GRC n°5, ONCOTYPE-URO, Paris, France

    Morgan Rouprêt

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  1. Mathieu Rouanne
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Correspondence to Mathieu Rouanne.

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Rouanne, M., Roumiguié, M., Houédé, N. et al. Development of immunotherapy in bladder cancer: present and future on targeting PD(L)1 and CTLA-4 pathways. World J Urol 36, 1727–1740 (2018). https://doi.org/10.1007/s00345-018-2332-5

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  • DOI: https://doi.org/10.1007/s00345-018-2332-5

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