Sign in Subscribe
Cancer research

Mutations in Effector Genes Predict Better Outcomes with PARPi and ARSi in HRD-Positive Metastatic Prostate Cancer

Strategic Insights

— 1 min read

Researchers at the Medical University of Sofia have conducted a multicenter, retrospective study to evaluate the predictive value of mutations in effector genes versus sensor genes in patients with metastatic castration-resistant prostate cancer (mCRPC) classified as homologous recombination deficiency (HRD)-positive. The study found that patients with effector mutations in genes such as BRCA1, BRCA2, and PALB2 demonstrated a statistically significant improvement in progression-free survival (PFS) and overall survival (OS) compared to those with sensor mutations.

Key Takeaways:

  • A multicenter, retrospective real-world study was conducted across 6 oncology hospitals in Bulgaria, involving 210 mCRPC patients treated with olaparib plus abiraterone.
  • Patients with effector mutations in HRR genes demonstrated a statistically significant improvement in PFS (median 20 months vs. 14 months, HR = 0.48, 95% CI: 0.252-0.914, P = .0294) and OS (median not yet reached at 16 months, HR = 0.38, 95% CI, 0.154-0.945, P = .0373).
  • Logistic regression analysis and propensity score matching (PSM) supported the findings, suggesting that effector mutations confer a greater clinical benefit from PARPi and ARSi.
  • The study highlights the heterogeneous predictive value of HRR gene alterations and suggests that mutation sub-class should guide treatment decisions in HRD-positive mCRPC.
  • The research has been peer-reviewed and published in Clinical Genitourinary Cancer.

Statistics:

  • 28% of 210 mCRPC patients screened via NGS harbored mutations in at least one HRR gene (nis = 58).
  • 27 patients had mutations in sensor genes (ATM, ATR, CHEK1, CHEK2, NBS1), while 31 patients had mutations in effector genes (BRCA1, BRCA2, PALB2, RAD51, FANCD2).
  • Median PFS for patients with effector mutations was 20 months, compared to 14 months for those with sensor mutations (HR = 0.48, 95% CI: 0.252-0.914, P = .0294).
  • Median OS for the sensor group was 19 months, while the effector group had not yet reached median OS at the time of analysis (HR = 0.38, 95% CI, 0.154-0.945, P = .0373).

Sources:

  • NewsRx. Studies from Medical University of Sofia in the Area of Prostate Cancer Described (Impact of HRR Gene Subclass on Clinical Outcomes of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer). Cancer Weekly. September 16, 2025; p 3528.
  • Impact of HRR Gene Subclass on Clinical Outcomes of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer. Clinical Genitourinary Cancer, 2025:102411.

Read more