Piotr Wysocki, Professor of Medicine and Head of the Department of Oncology at Jagiellonian University Hospital, shared on LinkedIn:

“In a multicenter observational study, 729 patients with metastatic castration-resistant prostate cancer (mCRPC) who participated in four previously completed prospective studies — PROCURE Biomarkers Platform: PROREPAIR-B (NCT03075735), PROSENZA (NCT02922218), PROSTAC (NCT02362620), and PROSABI (NCT02787837) were included.

BRCA1/2 mutations were detected in 96 patients (74% – somatic mutations, 26% – germinal), while other mutations (non-BRCA1/2 homologous recombination deficiency – non-BRCA-HRD) were present in 127 patients, and no HRD in 506 patients. All patients were treated with study-defined first-line treatments (abiraterone acetate, enzalutamide, docetaxel, or cabazitaxel).

The analysis demonstrated that mCRPC patients with BRCA1/2 mutations had significantly worse outcomes in terms of radiographic progression-free survival (rPFS), second progression-free survival (PFS2), and overall survival (OS) compared to other mCRPC patient groups (non-BRCA-HRD and no HRD).

The median outcomes were significantly poorer in the BRCA1/2-mutated patients compared to patients without BRCA1/2 mutations:

• • rPFS – 7.1 months v.10.3 months (HR for rPFS=1.7; 95%CI 1.32-2.19)
  • PFS2 – 12.6 months v. 15.9 months (HR for PFS2=1.81; 95%CI 1.44-2.27)
  • OS – 19.4 months v. 27.9 months (HR for OS=1.95; 95%CI 1.55-2.45)

The results of this analysis provide critical data suggesting the need for early assessment of BRCA1/2 status in prostate cancer patients demonstrating early signs of castration resistance to guide the first-line treatment of mCRPC optimally.

The availability of PARPi (olaparib) and abiraterone combination in the first-line treatment of mCRCP patients has dramatically changed the initial treatment strategy in this population. Olaparib and abiraterone combination has significantly improved the overall survival of BRCA1/2-mutated mCRCP patients (PROPEL study), thus transforming the poor prognostic factor into a crucial, positive predictive factor.”

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Source: Piotr Wysocki/LinkedIn

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