Association Between HRR Mutations, Outcomes in mCRPC

A recent analysis sought to better understand the prevalence and outcomes of patients with and without homologous recombination repair (HRR) mutations—somatic and germline—who initiated first-line metastatic castration-resistant prostate cancer (mCRPC) treatment with a novel hormonal therapy or a taxane.

Results of the investigation are presented at the American Society of Clinical Oncology 2023 Annual Meeting.

Further research is needed to better understand the association between HRR mutations and outcomes in patients with mCRPC.

David Olmos, MD, PhD, and colleagues enrolled 729 patients from the PROREPAIR-B, PROSENZA, PROSTVAC, and PROSABI studies to investigate the prevalence and outcomes of patients with or without HRR mutations who initiated first-line mCRPC treatment. Patients underwent paired somatic/germline DNA analyses and were subsequently stratified into BRCA, non-BRCA, and HRR non-BRCA subgroups.

Researchers reported on radiographic progression-free survival (rPFS), second objective disease progression (PFS2), and overall survival (OS). Associations between mutations and outcomes were assessed using inverse probability weighted Cox models.

Among the total patient population, 30.6% (n=223) were stratified as HRR, including 13.2% (n=96) BRCA, and 60.4% of patients were treated with a novel hormonal therapy, whereas 39.6% were treated with a taxane.

Researchers found that BRCA patients had significantly worse rPFS, PFS2, and OS than non-BRCA patients, and they also had significantly worse PFS2 and OS than HRR non-BRCA patients. They noted that there was no significant differences between the outcomes of somatic and germline BRCA patients.

“It is crucial to screen early for HRR mutations, particularly in BRCA1/2, to begin timely, targeted mCRPC treatment and improve prognosis,” study authors concluded.