The Emerging Role of PD-1/PD-L1-Targeting Immunotherapy in the Treatment of Metastatic Urothelial Carcinoma.
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.
['Gwynn|Morgan E|ME|', 'DeRemer|David L|DL|']
D000970:Antineoplastic Agents D060890:B7-H1 Antigen D006801:Humans D007167:Immunotherapy D061026:Programmed Cell Death 1 Receptor D016896:Treatment Outcome D001749:Urinary Bladder Neoplasms
urothelial carcinoma atezolizumab avelumab durvalumab nivolumab pembrolizumab programmed death protein 1 (PD-1)