Investig Clin Urol.  2018 Sep;59(5):285-296. 10.4111/icu.2018.59.5.285.

Immune checkpoint inhibitors for urothelial carcinoma

Affiliations
  • 1Department of Urology, Dongguk University Ilsan Medical Center, Dongguk University College of Medicine, Goyang, Korea.
  • 2Department of Urology, Center for Prostate Cancer, Hospital and Biomarker Branch, Research Institute, National Cancer Center, Goyang, Korea. seohk@ncc.re.kr

Abstract

Urothelial carcinoma (UC), originating in the bladder or upper urinary tract, is the most common histological type of cancer. Currently, platinum-based cytotoxic chemotherapy is the standard treatment for metastatic UC (mUC) and the preferred treatment option in the perioperative (neoadjuvant and/or adjuvant) setting of muscle invasive bladder cancer (MIBC). In addition, intravesical bacillus Calmette-Guerin immunotherapy or chemotherapy is applied as the adjuvant therapeutic option in non-muscle invasive bladder cancer (NMIBC) after transurethral resection, to prevent recurrence and progression. In recent years, with an increased understanding of cancer immunobiology, systemic immunotherapies targeting immune checkpoint inhibition has been explored and clinically used in the area of UC. The programmed cell death 1 receptor (PD-1) and its ligand (PD-L1) are important negative regulators of immune activity, preventing the destruction of normal tissues and autoimmunity. To date, five immune checkpoint inhibitors blocking PD-1 (pembrolizumab, nivolumab) or PD-L1 (atezolizumab, durvalumab, and avelumab) have been approved by the United States Food and Drug Administration (US-FDA) for first- or second-line use in mUC, based on durable therapeutic response and manageable safety profiles observed in relevant clinical trials. In addition, the clinical use of several immune checkpoint inhibitors is currently being tested for MIBC and NMIBC. In this article, we review the current and ongoing clinical trials, regarding immune checkpoint inhibitors, being conducted in various clinical settings of UC, including mUC, MIBC, and NMIBC.

Keyword

Immunotherapy; PD-1 inhibitor; PD-L1 inhibitor; Urinary bladder neoplasms

MeSH Terms

Autoimmunity
Bacillus
Drug Therapy
Immunotherapy
Programmed Cell Death 1 Receptor
Recurrence
United States Food and Drug Administration
Urinary Bladder
Urinary Bladder Neoplasms
Urinary Tract
Programmed Cell Death 1 Receptor

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