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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer
Antonio Lopez-Beltran1, Alessia Cimadamore2, Ana Blanca3
1Unit of Anatomic Pathology, Department of Morphological Sciences, Cordoba University Medical School, 14004 Cordoba, Spain.
Abstract:
A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
Insights
Immune checkpoint inhibitors (ICIs) show promise for metastatic urothelial carcinoma (mUC), with PD-L1 expression aiding treatment selection. Ongoing research explores ICIs in various settings and combinations for better patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinoma Research
Background:
- Immune checkpoint inhibitors (ICIs) are approved for metastatic urothelial carcinoma (mUC), offering treatment options for cisplatin-ineligible or second-line patients.
- Approximately 30% of mUC patients respond to ICI immunotherapy, with PD-L1 expression by immunohistochemistry emerging as a potential predictive biomarker.
- Several anti-PD-1 (Pembrolizumab, Nivolumab) and anti-PD-L1 (Atezolizumab, Durvalumab, Avelumab) antibodies have demonstrated efficacy, including improved overall survival (OS) and durable responses.
Purpose of the Study:
- To review clinical trial results of ICIs in mUC, focusing on monotherapy, combination therapy, and neoadjuvant/adjuvant settings.
- To examine the role of biomarkers, including PD-L1 expression, in predicting response to ICIs in mUC.
- To provide an overview of the current landscape and future directions for ICI therapy in mUC.
Main Methods:
- Review of clinical trial data for ICIs in mUC.
- Analysis of objective response rates (ORR) and overall survival (OS) associated with ICI treatment.
- Evaluation of biomarkers, particularly PD-L1 immunohistochemistry, for treatment selection.
Main Results:
- ICIs have shown significant efficacy in mUC, with some patients achieving durable responses exceeding one year.
- Pembrolizumab and Nivolumab (anti-PD-1) and Atezolizumab, Durvalumab, Avelumab (anti-PD-L1) are approved for specific mUC treatment lines.
- PD-L1 expression is a key biomarker, though further research is needed for optimal biomarker-guided therapy.
Conclusions:
- ICIs represent a significant advancement in mUC treatment, offering survival benefits for a subset of patients.
- The identification and validation of robust biomarkers are crucial for optimizing ICI therapy selection in mUC.
- Ongoing trials investigating ICIs in combination or in earlier disease settings hold promise for improving outcomes in mUC.
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