Abstract 358P
Background
The use of Homologous Recombination Deficiency (HRD) scores for treatment selection and predicting therapeutic efficacy is gaining traction. However, the predictive role of HRD scores in the efficacy of abiraterone for metastatic prostate cancer (PCa) remains unclear.
Methods
We retrospectively collected 72 patients who underwent genomic sequencing and were evaluated for HRD scores (unweighted sum of loss-of-heterozygosity, telomeric allelic imbalance, and large-scale state transitions). Of these, 35 patients received abiraterone at the metastatic hormone-sensitive prostate cancer (mHSPC) stage, while 37 were treated at the metastatic castration-resistant prostate cancer (mCRPC) stage. The associations between HRD scores and abiraterone efficacy were assessed, including prostate specific antigen (PSA) response, PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS) and overall survival (OS).
Results
In the mHSPC cohort, higher HRD scores (≥21) suggested potential trend towards deteriorating therapeutic response yet were not associated with significant changes in the evaluated endpoints. In the mCRPC cohort, men with higher HRD scores experienced significantly shorter PSA progression-free survival (median: 8.17 vs. 24.17 months, p=0.032), radiographic progression-free survival (median: 11.8 vs. 24.8 months, p=0.015), and overall survival (median: 36.5 months vs. not reached, p=0.056). Additionally, these men exhibited a lower PSA response (6/19 vs. 13/16, p=0.006). Cox regression analysis corroborated these findings. Regarding HRD scores-related mutations, in DDR-mut population, BRCA-2 mutations were associated with higher HRD scores (BRCA-2 mutation: n=5, median: 38 vs. 15, p=0.043). In DDR-wt population, AR pathway mutations were predominately correlated with elevated HRD scores (AR pathway mutation: n=16, median: 24.5 vs. 19.5, p=0.034).
Conclusions
HRD scores was associated with unfavorable therapeutic efficacy of abiraterone in mCRPC cohort. These findings could pave the way for therapeutic decision-making for PCa patients according to their HRD status. Further large-scale studies are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This work was supported by the National Natural Science Foundation of China (NSFC 82203110, 82172785, and 81974398), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC21020, ZYGD22004), Science and Technology Support Program of Sichuan Province (2021YFS0119), Clinical and Translational Medicine Research Project, Chinese Academy of Medical Sciences (2022-I2M-C&T-B-098), Bethune Foundation, Oncology Basic Research Program (X-J-2020-016), and Bethune Foundation, Urological Oncology Special Research Fund (mnzl202002, mnzl202007).
Disclosure
All authors have declared no conflicts of interest.