Molecular predictors of response to PD-1/PD-L1 inhibition in urothelial cancer

Area of Science:

• Oncology
• Immunotherapy
• Urothelial Carcinoma Research

Background:

• Metastatic urothelial cancer (mUC) has a poor prognosis, with chemotherapy as the primary treatment for decades.
• Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, have transformed cancer immunotherapy, offering new options for UC patients, especially those with recurrence or cisplatin ineligibility.

Purpose of the Study:

• To review the current landscape of immune checkpoint inhibitors (ICIs) in metastatic urothelial cancer (mUC).
• To identify the challenges in predicting patient response to ICI therapy.
• To highlight the need for validated biomarkers in UC treatment selection.

Main Methods:

• A comprehensive literature search was performed in May 2018.
• Databases searched included PubMed, ClinicalTrials.gov, and select annual congress abstracts.
• Keywords encompassed urothelial bladder cancer, immunotherapy, immune checkpoint inhibition, biomarkers, and PD1/PD-L1.

Main Results:

• While some patients achieve durable responses to ICIs, reliable prediction of treatment efficacy is currently not possible.
• Physicians face difficulties in selecting mUC patients most likely to benefit from ICI therapy.
• Exploratory analyses suggest potential predictive/prognostic value for PD-L1 expression, tumor mutation burden, tumor-infiltrating lymphocytes, and gene expression profiles.

Conclusions:

• Validated, robust biomarkers are essential to accurately predict response to ICI in urothelial cancer (UC) patients.
• Overcoming the current limitations in patient selection is critical for optimizing ICI therapy in UC.