Related Experiment Video
Updated: Nov 18, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Safety and Clinical Activity of Atezolizumab in Patients with Metastatic Castration-Resistant Prostate Cancer: A
Daniel P Petrylak1, Yohann Loriot2, David R Shaffer3
1Yale Cancer Center, New Haven, Connecticut. daniel.petrylak@yale.edu.
Purpose:
Atezolizumab [anti-programmed death-ligand 1 (anti-PD-L1)] is well tolerated and efficacious in multiple cancers, but has not been previously evaluated in metastatic castration-resistant prostate cancer (mCRPC). This study examined the safety, efficacy, and biomarkers of atezolizumab monotherapy for mCRPC.
Patients And Methods:
This phase Ia, open-label, dose-escalation and dose-expansion study (PCD4989g) enrolled patients with mCRPC who had progressed on sipuleucel-T or enzalutamide. Atezolizumab was given intravenously every 3 weeks until confirmed disease progression or loss of clinical benefit. Prespecified endpoints included safety, efficacy, biomarker analyses, and radiographic assessments.
Results:
All 35 evaluable patients [median age, 68 years (range, 45-83 years)] received atezolizumab after ≥1 prior line of therapy; 62.9% of patients had received ≥3 prior lines. Treatment-related adverse events occurred in 21 patients (60.0%), with no deaths. One patient had a confirmed partial response (PR) per RECIST 1.1, and 1 patient had a PR per immune-related response criteria. The confirmed 50% PSA response rate was 8.6% (3 patients). Median overall survival (OS) was 14.7 months [95% confidence interval (CI): 5.9-not evaluable], with a 1-year OS rate of 52.3% (95% CI: 34-70); 2-year OS was 35.9% (95% CI: 13-59). Median follow-up was 13.0 months (range, 1.2-28.1 months). Biomarker analyses showed that atezolizumab activated immune responses; however, a composite biomarker failed to reveal consistent correlations with efficacy.
Conclusions:
Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types. In heavily pretreated patients, atezolizumab monotherapy demonstrated evidence of disease control; however, its limited efficacy suggests a combination approach may be needed.
Insights
Atezolizumab, an anti-programmed death-ligand 1 (anti-PD-L1) therapy, showed acceptable safety in metastatic castration-resistant prostate cancer (mCRPC). While demonstrating some disease control, its limited efficacy suggests combination strategies may be more effective for mCRPC treatment.
Area of Science:
- Oncology
- Immunotherapy
- Prostate Cancer Research
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge with limited treatment options.
- Atezolizumab, a monoclonal antibody targeting the programmed death-ligand 1 (PD-L1) immune checkpoint, has shown efficacy in various cancers.
- The role of atezolizumab in mCRPC has not been previously established.
Purpose of the Study:
- To evaluate the safety and efficacy of atezolizumab monotherapy in patients with mCRPC.
- To explore potential biomarkers associated with atezolizumab treatment response in mCRPC.
- To assess the tolerability and preliminary activity of atezolizumab in a heavily pretreated mCRPC population.
Main Methods:
- A phase Ia, open-label, dose-escalation and expansion study (PCD4989g) was conducted.
- Patients with mCRPC progressing on sipuleucel-T or enzalutamide received intravenous atezolizumab every 3 weeks.
- Endpoints included safety, efficacy (including PSA response and radiographic assessment), and biomarker analyses.
Main Results:
- 35 evaluable patients with mCRPC received atezolizumab; 62.9% had received ≥3 prior lines of therapy.
- Treatment-related adverse events occurred in 60.0% of patients, with no treatment-related deaths.
- A confirmed partial response was observed in 1 patient per RECIST 1.1 and 1 patient per irRC. The 50% PSA response rate was 8.6%. Median overall survival was 14.7 months.
Conclusions:
- Atezolizumab was generally well tolerated in patients with mCRPC, with a safety profile consistent with other tumor types.
- In heavily pretreated mCRPC patients, atezolizumab monotherapy demonstrated evidence of disease control.
- The limited efficacy observed suggests that combination approaches may be necessary for improved outcomes in mCRPC.
