270P - Germline BRCA1/2 pathogenic variants in Japanese patients with prostate cancer are predictive factors for androgen receptor-axis-targeted therapy or chemotherapy for castration-resistant prostate cancer

Background

The companion diagnostic for olaparib against prostate cancer, which aims to detect BRCA1 or BRCA2 gene (BRCA1/2) variants, was investigated in December 2020 in Japan. There have been no reports on germline BRCA1/2 variants in actual clinical practice. Here, we evaluate germline BRCA1/2 variants and their relationship to the clinical characteristics and outcomes in prostate cancer.

Methods

Between June 2021 and June 2023, 92 patients with prostate cancer were examined using germline BRCA1/2 testing. Further, the associations between pathogenic variants and clinical outcomes were assessed.

Results

Of the 92 patients referred from the Iwate prefecture in Japan for genetic testing, six patients (6.5%) carried germline pathogenic variants; BRCA2 was the most frequent (n=5, 5.4%), followed by BRCA1 (n=1, 1.1%). Among the six variants in BRCA2, p.Ala338Valfs*11 was identified for the first time. Patients with the BRCA1/2 variant exhibited poor outcomes for overall survival from castration-resistant prostate cancer (CRPC), first-line androgen receptor-axis-targeted therapy (ARAT) for CRPC, and taxane chemotherapy (hazard ratio [HR] 4.77, 95% CI: 1.00 to 22.6, P=0.049; HR=5.27, 95% CI: 1.77 to 15.7, P=0.0028; and HR=7.47, 95% CI: 1.49 to 37.4, P=0.014, respectively).

Conclusions

In this study, patients with prostate cancer possessing germline variants of BRCA1/2 genes exhibited poor clinical response to ARAT for CRPC and taxane chemotherapy.

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.