PROREPAIR-B (NCT03075735)  is the first prospective study to report a worse survival from MCRPC patients with these associated germline mutations. This study demonstrated significant interactions between treatment-type (androgen signaling inhibitors [ASI]/Taxanes) and BRCA2 status with an effect on cause-specific survival (CSS) from 1st line (p = 0.015) and 2nd line (p = 0.006).
The authors present an exploratory sub-analysis, demonstrating the treatment outcomes based on BRCA2 carrier status and the treatment sequence these patients received.
This was a prospective multicenter observational cohort study (Figure 1).
Patients with unknown mutational status at study entry beginning therapy for MCRPC were included in this study. For this specific study, patients who were taxane and androgen signaling inhibitor (ASI) naïve at the time of MCRPC were eligible. All patients were screened for germline mutations in a panel of 107 DDR genes. The objective was to assess the impact of germline BRCA2 mutations on cancer specific survival (CSS) and progression free survival (PFS) from 1st line therapy initiation to progression to 2nd line therapy or death. Two different treatment sequences were compared (ASI/taxanes vs. taxanes/ASI).
The results demonstrated that 348 out of 419 patients were eligible for this analysis: 190 patients (7 BRCA2) for the ASI-taxane sequence and 178 (7 BRCA2) for the taxane-ASI sequence. Table 1 demonstrates the demographic and clinical characteristics of these patients.
No significant differences in outcome between BRCA2 carriers and non-carriers were observed with the ASI-taxane sequence. However, in the taxane-ASI sequence BRCA2 carrier status conferred significantly worse CSS (10.7 vs. 28.4 months, p<0.001) and PFS (8.6 vs. 17.1 months, p<0.001). Multivariable analyses demonstrated that BRCA2 status remained an independent prognostic factor for CSS (HR 4.16, CI 95% 1.8-7.15), and PFS (HR 5.5, 95% CI 2.35-12.89 in patients treated first with taxanes.
The authors concluded that outcomes o BRCA2 mutation carriers may differ according to treatment sequences. This contributes to explain the differences in outcomes reported by previous series.
Presented by: Nuria Romero-Laorden, Hospital Universitario La Princesa, Madrid, Spain
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA
 Castro et al. ESMO 2017