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Updated: Oct 7, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a
Thomas Powles1, Kobe C Yuen2, Silke Gillessen3,4
1Barts Cancer Institute, Queen Mary University of London, London, UK. thomas.powles1@nhs.net.
Abstract:
Early clinical data indicate that some patients with castration-resistant prostate cancer may benefit from program death ligand-1 (PD-L1) inhibition, especially with enzalutamide. The IMbassador250 trial (no. NCT03016312) enrolled 759 men with metastatic castration-resistant prostate cancer whose disease progressed on abiraterone. The addition of atezolizumab to enzalutamide in an open-label randomized trial did not meet the primary endpoint of improved overall survival in unselected patients (stratified hazard ratio 1.12, 95% confidence interval (0.91, 1.37), P = 0.28), despite an acceptable safety profile. In archival tumor samples, prostate tumors showed comparatively low expression of key immune biomarkers. DNA damage-response alterations, phosphatase and tensin homolog status and PD-L1 expression levels were similar between hormone-sensitive and castration-resistant prostate cancers. In planned biomarker analysis, longer progression-free survival was seen with atezolizumab in patients with high PD-L1 IC2/3, CD8 expression and established immune gene signatures. Exploratory analysis linked progression-free survival in the atezolizumab arm with immune genes such as CXCL9 and TAP1, together with other potentially relevant biomarkers including phosphatase and tensin homolog alterations. Together these data indicate that the expected biology associated with response to immune checkpoint inhibitors is present in prostate cancer, albeit in fewer patients. Careful patient selection may be required for immune checkpoint inhibitors to identify subgroups of patients who may benefit from this treatment approach.
Insights
Adding atezolizumab to enzalutamide did not improve overall survival in metastatic castration-resistant prostate cancer. Biomarker analysis suggests potential benefit in select patients with high PD-L1 expression.
Area of Science:
- Oncology
- Immunotherapy
- Prostate Cancer Research
Background:
- Early data suggested potential benefit from program death ligand-1 (PD-L1) inhibition in castration-resistant prostate cancer (CRPC).
- Enzalutamide is a standard treatment for CRPC, and combination therapies are being explored.
Purpose of the Study:
- To evaluate the efficacy of adding atezolizumab to enzalutamide in men with metastatic CRPC.
- To identify potential biomarkers predictive of response to atezolizumab plus enzalutamide.
Main Methods:
- The IMbassador250 trial was an open-label, randomized study of 759 men with metastatic CRPC progressing on abiraterone.
- Patients received either enzalutamide alone or enzalutamide plus atezolizumab.
- Archival tumor samples were analyzed for immune biomarkers, DNA damage-response alterations, and phosphatase and tensin homolog (PTEN) status.
Main Results:
- The addition of atezolizumab did not meet the primary endpoint of improved overall survival (HR 1.12; P=0.28).
- Prostate tumors generally showed low expression of key immune biomarkers.
- Biomarker analyses indicated longer progression-free survival with atezolizumab in patients with high PD-L1 expression (IC2/3), CD8 counts, and immune gene signatures.
Conclusions:
- Atezolizumab plus enzalutamide did not improve overall survival in unselected patients with metastatic CRPC.
- Prostate cancer exhibits the immune biology for response to immune checkpoint inhibitors, but in a subset of patients.
- Careful patient selection based on biomarkers may be necessary to identify subgroups who could benefit from atezolizumab therapy.
