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The landscape of immunotherapy in metastatic urothelial carcinoma
1Genitourinary Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Purpose Of Review:
This review provides an overview of clinical trials recently completed or currently ongoing evaluating the role of checkpoint blockade in metastatic urothelial carcinoma.
Recent Findings:
In 2016, five immunotherapy agents were approved for metastatic urothelial carcinoma patients who had progressed on platinum-based chemotherapy All five agents evinced an approximately 20% overall response rate coupled with durability of response in a subset of these patients. Several putative predictive biomarkers of sensitivity to checkpoint blockade have been examined although which of these should be incorporated into standard practice is unclear. Moreover, as most patients do not respond to checkpoint blockade, research has focused on combination therapies in both the first-line and second-line settings.
Summary:
The durability of response and general tolerability of checkpoint blockade has transformed the treatment of metastatic urothelial carcinoma. However, only a minority of patients responds to single-agent therapy. Potential approaches to overcome this challenge include the incorporation of combination checkpoint blockade as well as chemotherapy and targeted agents.
Insights
Checkpoint blockade immunotherapy offers durable responses in metastatic urothelial carcinoma. Combination therapies are being explored to improve response rates in patients with this cancer.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinoma Research
Background:
- Metastatic urothelial carcinoma treatment has been transformed by immunotherapy.
- Checkpoint blockade agents show durable responses in a subset of patients.
- High response rates are not achieved with single-agent therapies.
Purpose of the Study:
- To review recent clinical trials on checkpoint blockade for metastatic urothelial carcinoma.
- To discuss the role of immunotherapy in treating advanced urothelial cancer.
Main Methods:
- Review of completed and ongoing clinical trials.
- Analysis of immunotherapy agents approved in 2016.
- Examination of predictive biomarkers for checkpoint blockade sensitivity.
Main Results:
- Five immunotherapy agents approved in 2016 demonstrated ~20% overall response rates.
- Durable responses observed in a subset of patients treated with checkpoint blockade.
- Uncertainty remains regarding the clinical utility of predictive biomarkers.
Conclusions:
- Checkpoint blockade has revolutionized metastatic urothelial carcinoma treatment.
- Improving response rates necessitates combination strategies.
- Future research focuses on combining checkpoint blockade with chemotherapy and targeted agents.
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