The FDA’s approval of the PD-L1 inhibitor atezolizumab to treat platinum-resistant mUC was based on results from a phase 2 trial indicating a 15% overall response rate (ORR) and a 27% ORR among patients with higher PD-L1 expression, among whom median overall survival was 11.9 months. The safety profile was also favorable.2

The FDA approved nivolumab based on a single-arm study treating patients with locally advanced or mUC who progressed during or after undergoing platinum-based chemotherapy. The ORR was 19.6% (95% CI: 15.1-24.9).3


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The tumor microenvironment may be used as a predictive biomarker of response to these immunotherapies: PD-L1 expression on tumors and tumor-infiltrating immune cells as well as increased mutation-associated neoantigen load, for example, correlate with high responses to inhibition of immunomodulatory checkpoints.

“The ideal biomarker to predict response to treatment is still a matter of intense research,” explained the authors.

“PD-L1 expression appears to predict better response to monotherapy only in patients previously treated with chemotherapy, and results have been inconsistent across mUC trials. Assays need to be compared and standardized before they can be used to select patients for therapy.”

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These recent advances and current clinical trials bode well for achieving increased remissions, improved response rates, faster development of immunotherapy agents, appropriate application of combination treatments, and progress in new targets for immunotherapy.

References

  1. Davarpanah NN, Yuno A, Trepel JB, Apolo AB. Immunotherapy: a new treatment paradigm in bladder cancer. Curr Opin Oncol. 2017 Mar 16. doi: 10.1097/CCO.0000000000000366 [Epub ahead of print]
  2. Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016;387(10031):1909-20. doi: 10.1016/S0140-6736(16)00561-4
  3. Sharma P, Retz M, Siefker-Radtke A, et al. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2017;18(3):312-22. doi: 10.1016/S1470-2045(17)30065-7