Checkpoint inhibitors: the new treatment paradigm for urothelial bladder cancer

@article{Katz2017CheckpointIT,
  title={Checkpoint inhibitors: the new treatment paradigm for urothelial bladder cancer},
  author={Heather Katz and Emnet A. Wassie and M. Alsharedi},
  journal={Medical Oncology},
  year={2017},
  volume={34},
  pages={1-11}
}
Bladder cancer is the most common malignancy involving the genitourinary system (Siegel et al. in CA Cancer J Clin, 66:7–30, 2016). In the USA, it is the fifth most common cancer and approximately 79,000 new cases will be diagnosed in 2017 (Siegel et al. in CA Cancer J Clin, 66:7–30, 2016). The mortality from bladder cancer is approximately 17,000 deaths each year (Siegel et al. in CA Cancer J Clin, 66:7–30, 2016). The incidence rate for bladder cancer is higher in men compared to women. Risk… 
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References

SHOWING 1-10 OF 31 REFERENCES
Systemic Immunotherapy for Urothelial Cancer: Current Trends and Future Directions
TLDR
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 represents a significant milestone in this disease.
Immunotherapy for Patients with Advanced Urothelial Cancer: Current Evidence and Future Perspectives
TLDR
The rationale for the use of immunotherapy in bladder cancer is described, recent and ongoing clinical trials with checkpoint inhibitors and other novel immunotherapy agents are discussed and anti-cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibodies are discussed.
Pembrolizumab as Second‐Line Therapy for Advanced Urothelial Carcinoma
TLDR
Pembrolizumab was associated with significantly longer overall survival and with a lower rate of treatment‐related adverse events than chemotherapy as second‐line therapy for platinum‐refractory advanced urothelial carcinoma.
Pembrolizumab as first-line therapy in cisplatin-ineligible advanced urothelial cancer: Results from the total KEYNOTE-052 study population.
TLDR
First-line pembrolizumab (pembro) had antitumor activity and acceptable safety in this pt population suggested in the phase 2, open-label KEYNOTE-052 study.
Avelumab in patients with metastatic urothelial carcinoma: Pooled results from two cohorts of the phase 1b JAVELIN Solid Tumor trial.
TLDR
A planned interim pooled analysis of 2 cohorts from a large phase 1b trial of avelumab with promising efficacy and safety in patients with metastatic urothelial carcinoma is reported.
Safety and Efficacy of Durvalumab (MEDI4736), an Anti-Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer.
  • C. Massard, M. Gordon, N. Segal
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2016
TLDR
Durvalumab demonstrated a manageable safety profile and evidence of meaningful clinical activity in PD-L1-positive patients with UBC, many of whom were heavily pretreated.
...
...