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PD-1/PD-L1 for prostate cancer: from clinical trials to practice
Aaron Holmes1,2, Tobechukwu Okobi3, Abdul Baseet Arham1,2
1Division of Hematology/Oncology, Weill Cornell Medicine, New York, NY, USA.
Introduction:
A growing number of malignancies have shown favorable responses to immune checkpoint inhibitors (ICI), most commonly anti-PD-(L)1 antibodies. However, prostate cancer has been associated with mostly unfavorable responses to ICI. This review discusses various trials related to PD-(L)1 inhibitors in prostate cancer.
Areas Covered:
We wrote a review article based upon content and practice expertise supplemented with review of the literature. The focus was on PD-1 or PD-L1 inhibitors in prostate cancer.
Expert Opinion:
Clinical trials with PD-(L)1 inhibitors in patients with prostate cancer administered alone or in combination with other therapies do not appear to have significant benefit in unselected patients, whether part of initial systemic therapy or after the development of hormone resistance. However, there may be benefits in selected tumors harboring mutations with microsatellite instability high/mismatch repair deficiency (MSI-H/dMMR) and, to a lesser extent, high tumor mutational burden (TMB-H). While only a small percentage of prostate tumors have these mutations (MSI-H/dMMR: 3%) and (TMB-H: 4.5%), panel genomic testing can help identify subsets of patient populations who may benefit from PD-(L)1 inhibitors in addition to other molecularly selected agents.
Insights
Prostate cancer shows poor response to immune checkpoint inhibitors (ICI) like anti-PD-(L)1 antibodies in most patients. However, selected tumors with MSI-H/dMMR or TMB-H may benefit from these therapies.
Area of Science:
- Oncology
- Immunotherapy
- Genitourinary Cancers
Background:
- Immune checkpoint inhibitors (ICIs), particularly anti-PD-(L)1 antibodies, have transformed cancer treatment.
- Prostate cancer (PC) has historically demonstrated limited efficacy with ICI therapy.
- Understanding predictive biomarkers is crucial for optimizing ICI treatment in PC.
Purpose of the Study:
- To review clinical trials of PD-(L)1 inhibitors in prostate cancer.
- To identify patient subsets who may benefit from ICI therapy.
- To discuss the role of molecular profiling in guiding treatment decisions.
Main Methods:
- Comprehensive literature review of clinical trials involving PD-(L)1 inhibitors in prostate cancer.
- Analysis of treatment outcomes based on patient selection and tumor characteristics.
- Evaluation of the impact of specific genetic mutations on ICI response.
Main Results:
- PD-(L)1 inhibitors, alone or in combination, show limited benefit in unselected prostate cancer patients.
- A subset of patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors may respond to PD-(L)1 inhibitors.
- High tumor mutational burden (TMB-H) is also associated with potential benefit, albeit to a lesser extent.
Conclusions:
- Current PD-(L)1 inhibitor strategies offer minimal benefit for the general prostate cancer population.
- Genomic testing to identify MSI-H/dMMR or TMB-H mutations is essential for patient selection.
- Targeted application of PD-(L)1 inhibitors in molecularly selected PC patients may improve outcomes.
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