The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma

Abstract

Objective: To summarize and evaluate immunotherapy agents targeting programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) recently approved for the treatment of metastatic urothelial carcinomas (UC).

Data sources: A literature review was performed using PubMed (2012 to June 2017), the American Society of Clinical Oncology abstract databases (2012 to June 2017 Annual Meetings/symposia), and the America Association for Cancer Research symposia (2012 to June 2017). A search using clinicaltrials.gov was conducted to identify studies for atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab.

Study selection and data extraction: English language phase I to III studies assessing PD-1 and PD-L1 in UC were incorporated.

Data synthesis: Atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab have demonstrated clinical efficacy with tolerable toxicities in patients with metastatic UC with disease progression following platinum-based chemotherapy. Anti-PD-1/PD-L1 therapies may provide overall survival advantage; these are currently being evaluated in ongoing phase 3 studies. Greater objective response rates seem to be observed in PD-L1-positive patients versus PD-L1-negative patients, but methodologies in this assessment differ among clinical trials. The identification of biomarkers that provide greater insight into patients who positively respond to PD-1/PD-L1 therapies are needed.

Conclusions: Treatment options for metastatic UC have expanded to include PD-1/PD-L1 therapies. These agents should be strongly considered as second-line therapy over single-agent chemotherapy for patients who fail or progress after platinum-based treatment.

Keywords: atezolizumab; avelumab; durvalumab; nivolumab; pembrolizumab; programmed death protein 1 (PD-1); urothelial carcinoma.