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A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2024 Jan 23
PMID 38254823
Authors
Affiliations
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Abstract

Urothelial cancer is an immune-responsive cancer, but only a subset of patients benefits from immune checkpoint inhibition. Currently, single-agent immune checkpoint inhibitors (ICIs) and the combination of pembrolizumab with the antibody-drug conjugate enfortumab vedotin are approved to treat patients with metastatic UC (mUC). Approval of first-line nivolumab in combination with gemcitabine and cisplatin is expected imminently. Many treatment approaches are being investigated to better harness the immune system to fight mUC. In this review, we summarize the landmark clinical trials of ICIs that led to their incorporation into the current standard of care for mUC. We further discuss recent and ongoing clinical trials in mUC, which are investigating ICIs in combination with other agents, including chemotherapy, antibody-drug conjugates, tyrosine kinase inhibitors, and novel antibodies. Lastly, we review novel approaches utilizing bispecific antibodies, cellular therapies, and vaccines. The landscape of immunotherapy for mUC is rapidly evolving and will hopefully lead to better outcomes for patients.

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References
1.
Matsumoto K, Noguchi M, Satoh T, Tabata K, Fujita T, Iwamura M . A phase I study of personalized peptide vaccination for advanced urothelial carcinoma patients who failed treatment with methotrexate, vinblastine, adriamycin and cisplatin. BJU Int. 2010; 108(6):831-8. DOI: 10.1111/j.1464-410X.2010.09933.x. View

2.
Apolo A, Ellerton J, Infante J, Agrawal M, Gordon M, Aljumaily R . Avelumab as second-line therapy for metastatic, platinum-treated urothelial carcinoma in the phase Ib JAVELIN Solid Tumor study: 2-year updated efficacy and safety analysis. J Immunother Cancer. 2020; 8(2). PMC: 7549450. DOI: 10.1136/jitc-2020-001246. View

3.
Sweeney C, Roth B, Kabbinavar F, Vaughn D, Arning M, Curiel R . Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006; 24(21):3451-7. DOI: 10.1200/JCO.2005.03.6699. View

4.
Balar A, Kamat A, Kulkarni G, Uchio E, Boormans J, Roumiguie M . Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol. 2021; 22(7):919-930. DOI: 10.1016/S1470-2045(21)00147-9. View

5.
Qu Y, Sun Z, Han W, Zou Q, Xing N, Luo H . Camrelizumab plus famitinib for advanced or metastatic urothelial carcinoma after platinum-based therapy: data from a multicohort phase 2 study. J Immunother Cancer. 2022; 10(5). PMC: 9092172. DOI: 10.1136/jitc-2021-004427. View