Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects.

Area of Science:

• Oncology
• Genitourinary Cancers
• Cancer Immunology

Background:

• Immune checkpoint inhibitors (ICIs) show limited efficacy in metastatic castration-resistant prostate cancer (mCRPC).
• DNA repair defects (DRD) are hypothesized to increase neoantigen load and predict response to ICIs.
• Identifying predictive biomarkers for mCRPC patients is crucial for optimizing ICI therapy.

Purpose of the Study:

• To investigate the potential of DNA repair defects (DRD) as a predictive biomarker for response to nivolumab in patients with mCRPC.
• To evaluate the clinical activity of nivolumab in mCRPC patients with and without DRD.

Main Methods:

• A phase II, multicenter, single-arm trial was conducted in patients with mCRPC previously treated with docetaxel.
• DNA repair defects (DRD) were assessed using circulating tumor DNA (ctDNA) and whole-exome sequencing.
• Primary endpoint was Prostate-Specific Antigen (PSA) 50% response; secondary endpoints included objective response rate, progression-free survival, and overall survival.

Main Results:

• DRD was identified in 30.5% of patients via ctDNA and/or whole-exome sequencing.
• The overall PSA50 response rate was 10.5%.
• No significant differences in PSA50 response, objective response rate, or progression-free survival were observed between patients with and without DRD.

Conclusions:

• Nivolumab demonstrates clinical activity in a subset of mCRPC patients, but DRD does not appear to be a predictive biomarker.
• New biomarkers are required to identify mCRPC patients most likely to benefit from ICI therapy.