Focus on Biochemical and Clinical Predictors of Response to Immune Checkpoint Inhibitors in Metastatic Urothelial Carcinoma: Where Do We Stand?

Int J Mol Sci. 2020 Oct 26;21(21):7935. doi: 10.3390/ijms21217935.

Abstract

Urothelial bladder cancer is one of the most lethal cancers worldwide with barely 5% five-year survival in patients with metastatic disease. Intravesical immunotherapy with Bacillus Calmette-Guérin and platinum-based chemotherapy are currently the standard of care for non-muscle invasive and advanced or metastatic urothelial cancer (mUC), respectively. Recently, a subset of patients with locally advanced or mUC has shown to be responsive to immune checkpoint inhibitors (ICIs), e.g., the anti-cytotoxic T-lymphocyte-associated protein 4 and programmed cell death -1/programmed death-ligand1 (PD-1/PD-L1) antibodies. Due to the relevant clinical benefit of immunotherapy for mUC, in 2016, the United States Food and Drug Administration (FDA) approved five immunotherapeutic agents as second-line or first-line treatments for patients with advanced bladder cancer who did not profit from or were ineligible for standard therapy. In this review, we discuss the role of immunotherapy in bladder cancer and recent clinical applications of PD-1/PD-L1 blockade in mUC. Furthermore, we evaluate a variable response rate to ICIs treatment and outline potential biomarkers predictive of immunotherapy response.

Keywords: PD-1; PD-L1; biomarkers; bladder cancer.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B7-H1 Antigen / metabolism
  • CTLA-4 Antigen / metabolism
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / metabolism
  • Clinical Trials as Topic
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Neoplasm Metastasis
  • Programmed Cell Death 1 Receptor / metabolism
  • Treatment Outcome
  • United States
  • United States Food and Drug Administration
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / metabolism

Substances

  • Antineoplastic Agents, Immunological
  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immune Checkpoint Inhibitors
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor