Systemic immunotherapy for urothelial cancer: Current trends and future directions

Shilpa Gupta, David Gill, Austin Poole, Neeraj Agarwal

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

Urothelial cancer of the bladder, renal pelvis, ureter, and other urinary organs is the fifth most common cancer in the United States, and systemic platinum-based chemotherapy remains the standard of care for first-line treatment of advanced/metastatic urothelial carcinoma (UC). Until recently, there were very limited options for patients who are refractory to chemotherapy, or do not tolerate chemotherapy due to toxicities and overall outcomes have remained very poor. While the role of immunotherapy was first established in non-muscle invasive bladder cancer in the 1970s, no systemic immunotherapy was approved for advanced disease until the recent approval of a programmed death ligand-1 (PD-L1) inhibitor, atezolizumab, in patients with advanced/metastatic UC who have progressed on platinum-containing regimens. This represents a significant milestone in this disease after a void of over 30 years. In addition to atezolizumab, a variety of checkpoint inhibitors have shown a significant activity in advanced/metastatic urothelial carcinoma and are expected to gain Food and Drug Administration (FDA) approval in the near future. The introduction of novel immunotherapy agents has led to rapid changes in the field of urothelial carcinoma. Numerous checkpoint inhibitors are being tested alone or in combination in the first and subsequent-line therapies of metastatic disease, as well as neoadjuvant and adjuvant settings. They are also being studied in combination with radiation therapy and for non-muscle invasive bladder cancer refractory to BCG. Furthermore, immunotherapy is being utilized for those ineligible for first-line platinum-based chemotherapy. This review outlines the novel immunotherapy agents which have either been approved, or are currently being investigated in clinical trials in UC.

Original languageEnglish (US)
Article number15
JournalCancers
Volume9
Issue number2
DOIs
StatePublished - Feb 2017

Bibliographical note

Funding Information:
Acknowledgments: Funding: This study was supported in whole or in part by funding from the Cancer Clinical Investigator Team Leadership Award awarded by the National Cancer Institute through a supplement to P30CA042014.

Publisher Copyright:
© 2017 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

  • Bladder cancer
  • Immunotherapy
  • Urothelial carcinoma

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