Abstract 357P
Background
Homologous recombination repair gene mutations (HRRm) are found in approximately 25% of metastatic castration-resistant prostate cancer (mCRPC) cases. BRCA gene mutations, in particular, are associated with a more aggressive clinical course. The PROfound trial demonstrated the efficacy of PARP inhibitors in mCRPC with BRCA gene mutations. However, the effectiveness of androgen receptor signaling inhibitors (ARSIs) and chemotherapy in HRRm cases remains controversial. This study investigated the efficacy and clinical outcomes of ARSIs and taxane-based chemotherapy in mCRPC patients with HRRm.
Methods
We included mCRPC patients who underwent comprehensive genomic profiling (CGP) between March 2021 and July 2024. Patients were stratified based on the presence or absence of HRRm. The primary endpoint was PSA50/PSA90 response (≥50% or ≥90% reduction from baseline) to first-line ARSI treatment in both groups. Secondary endpoints included PSA30/PSA50 response (≥30% or ≥50% reduction) to docetaxel and overall survival from CGP submission and initial diagnosis in both groups.
Results
CGP was performed on 28 patients, with HRRm identified in 18 (64.3%) cases (ATM: 8, BRCA2: 5, BRCA1: 2, CDK12: 2, others: 3). The median age at diagnosis was 65 years, and median PSA was 44.5 ng/ml. Five patients each had undergone radical prostatectomy and radiation therapy with curative intent. There was no significant association between PSA50/PSA90 response to ARSIs and HRRm status (p = 0.68 and p = 0.21, respectively). Similarly, no significant association was found between PSA30/PSA50 response to docetaxel and HRRm status (p = 0.54 and p = 0.28, respectively). The median overall survival from CGP submission and initial diagnosis was 10.6 months and 170.1 months in the HRRm-positive group, and 12.3 months and 113.4 months in the HRRm-negative group, respectively. There was no evidence that OS differed based on HRRm status.
Conclusions
This study found no association between the treatment efficacy of ARSIs or taxane-based chemotherapy and HRRm status in mCRPC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.