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Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition

Nature Reviews Urology volume 15, pages 112–124 (2018)Cite this article

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Abstract

Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma. Treatment experience with immunotherapy suggests that these drugs are associated with a unique spectrum of immune-related adverse events and specific immune-related patterns of response, including cases of pseudoprogression, which could impede the optimal use of immune checkpoint inhibitors in the clinic. Appropriate management of immune-related adverse events and a greater awareness of immune-mediated response patterns will help to inform treatment decisions and improve patient outcomes; predictive biomarkers of response might facilitate selection of patients who are most likely to respond to and benefit from these exciting new treatments.

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Figure 1: The programmed death pathway.
Figure 2: CT images from a patient with pseudoprogression following treatment with nivolumab.

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Acknowledgements

The authors thank M. Soushko and L. Hargett for editorial assistance, funded by Bristol-Myers Squibb.

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Authors and Affiliations

  1. The University of Texas MD Anderson Cancer Center, 1155 Pressler, Unit 1374, Houston, 77030, Texas, USA

    Arlene Siefker-Radtke

  2. Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan, Suite 2N82, Portland, 97213, Oregon, USA

    Brendan Curti

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  1. Arlene Siefker-Radtke
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Both authors researched data for the article, made substantial contributions to discussions of content, wrote the article, and reviewed and edited the manuscript before submission.

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Correspondence to Arlene Siefker-Radtke.

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Competing interests

A.S.-R. declares associations with AstraZeneca, Bristol-Myers Squibb (BMS), Eisai, EMD Serono, Genentech, Janssen, Merck, Threshold Pharmaceuticals, Inovio, and Vertex as a member of the scientific advisory boards and has acted as a speaker and preceptor for Genentech. B.C. declares receipt of honoraria from Prometheus Pharmaceuticals; research funding from BMS, MedImmune, and Prometheus Pharmaceuticals; and funding for travel expenses from BMS, MedImmune, and Prometheus Pharmaceuticals.

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Siefker-Radtke, A., Curti, B. Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. Nat Rev Urol 15, 112–124 (2018). https://doi.org/10.1038/nrurol.2017.190

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