New Settings for Immune Checkpoint Inhibitors in Urothelial Cancer

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Arlene O. Siefker-Radtke
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The advent of immune checkpoint inhibitors (ICIs) has changed the game in cancer immunotherapy, specifically in the treatment of urothelial bladder cancer. Several clinical trials combining chemotherapy with ICIs have resulted in approvals from the FDA and subsequent revisions within the NCCN Guidelines. The current NCCN Guidelines for Bladder Cancer reflect the most up-to-date, evidence-based data relating to the evaluation and management of urothelial bladder cancer. ICIs have been incorporated into the guidelines as maintenance therapy in response to chemotherapy, sequencing after disease progression from frontline chemotherapy, and for the treatment of non–muscle-invasive bladder cancer.

Disclosures: Dr. Siefker-Radtke has disclosed serving as a scientific advisor for AstraZeneca Pharmaceuticals LP, Bavarian Nordic, Bristol Myers Squibb Company, Genentech, Inc., Immunomedics, Inc., Janssen Pharmaceutica Products, LP, Merck & Co., Inc., Mirati Therapeutics, Inc., Nektar Therapeutics, Seattle Genetics, Inc., and Taiho Pharmaceuticals Co., Ltd.

Correspondence: Arlene O. Siefker-Radtke, MD, The University of Texas MD Anderson Cancer Center, 1155 Hermann Pressler, Unit 1374, Houston, TX 77030. Email: asiefker@mdanderson.org
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  • 1.

    Siefker-Radtke AO, Millikan RE, Tu S, et al. Phase III trial of fluorouracil, interferon alfa-2b, and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in metastatic or unresectable urothelial cancer. J Clin Oncol 2002;20:13611367.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Bellmunt J, de Wit R, Vaughn DJ, et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 2017;376:10151026.

  • 3.

    Jiang Q, Fu Q, Chang Y, et al. CD19+ tumor-infiltrating B-cells prime CD4+ T-cell immunity and predict platinum-based chemotherapy efficacy in muscle-invasive bladder cancer. Cancer Immunol Immunother 2019;68:4556.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Shin J, Chung J, Kim SH, et al. Effect of platinum-based chemotherapy on PD-L1 expression on tumor cells in non-small cell lung cancer. Cancer Res Treat 2019;51:10861097.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Galsky MD, Wang H, Hahn NM, et al. Phase 2 trial of gemcitabine, cisplatin, plus ipilimumab in patients with metastatic urothelial cancer and impact of DNA damage response gene mutations on outcomes. Eur Urol 2018;73:751759.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Kim WS, Kim H, Kwon KW, et al. Cisplatin induces tolerogenic dendritic cells in response to TRL agonists via the abundant production of IL-10, thereby promoting TH2- and Tr1-biased T-cell immunity. Oncotarget 2016;7:3376533782.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Hoimes CJ, Albany C, Hoffman-Censits J, et al. Neoadjuvant pembrolizumab plus cisplatin and gemcitabine shows promise in locally advanced urothelial cancer [abstract]. Presented at the ESMO Congress 2018; October 1923, 2018; Munich, Germany. Abstract LBA 33.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Grande E, Galsky MD, Arranz Arija JA, et al. IMvigor130: a phase III study of atezolizumab with or without platinum-based chemotherapy in previously untreated metastatic urothelial carcinoma [abstract]. Presented at the ESMO Congress 2019; September 27–October 1, 2019; Barcelona, Spain. Abstract LBA 14.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Hoimes CJ, Rosenberg JE, Srinivas S, et al. EV-103: initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma [abstract]. Presented at the ESMO Congress 2019; September 27–October 1, 2019; Barcelona, Spain. Abstract 4844.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Powles T, Park SH, Voog E, et al. 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 [abstract]. Presented at the ASCO20 Virtual Scientific Program; May 29–31, 2020. Abstract LBA1.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Flaig TW, Spiess PE, Agarwal N, et al. NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 2.2021. Accessed March 27, 2021. Available at NCCN.org

    • PubMed
    • Export Citation
  • 12.

    Powles T, van der Heijden MS, Castellano D, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet 2020;21:15741588.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Bajorin DF, Witjes JA, Gschwend J, et al. First results from the phase 3 CheckMate 274 trial of adjuvant nivolumab vs placebo in patients who underwent radical surgery for high-risk muscle-invasive urothelial carcinoma [abstract]. Presented at the ASCO 2021 Genitourinary Cancers Symposium; February 11–13, 2021. Abstract 391.

    • PubMed
    • Export Citation
  • 14.

    Balar AV, Kamat AM, Kulkarni GS, et al. Pembrolizumab for the treatment of patients with Bacillus Calmette-Guérin unresponsive, high-risk non–muscle-invasive bladder cancer: over two years follow-up of KEYNOTE-057 [abstract]. Presented at the ASCO20 Virtual Scientific Program; May 29–31, 2020. Abstract 5041.

    • PubMed
    • Search Google Scholar
    • Export Citation
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