Outcomes of Metastatic Castration Resistant Prostate Cancer (mcrpc) Patients with DNA Repair Germline Mutations (gddr) Following First Taxane-Based Treatment.

247 Background: Germline DDR have been identified in up to 12% of mCRPC patients. Initial results from various retrospective series have reported discordant impact in clinical outcomes associated to these gDDR following conventional treatments. PROREPAIR-B (Castro et al ESMO 2017) is the first prospective study to address this question. In this planned sub-analysis, we report mCRPC treatment outcomes associated to taxanes. Methods: PROREPAIR-B (NCT03075735) is a prospective multicentre observational cohort study. Patients diagnosed with mCRPC, with unknown mutational status at study entry and who were going to start a first-line treatment for mCRPC were eligible. For this sub-analysis patients who received docetaxel or cabazitaxel as first-taxane were selected. The endpoints of this sub-analysis included to assess the impact of BRCA1, BRCA2, ATM and PALB2 and other gDDR on cause-specific survival (CSS), progression free survival (PFS), time to PSA progression (bPFS) and response to the first administered taxane as 1st or 2nd line therapy. Results: 326 (12 BRCA2, 8 ATM and 1 BRCA1 mutation carrier [gMUT]) out of 419 patients were eligible for this analysis. Diagnostic characteristic included Stage IV 51%, G8-10 60%. At the time of taxane initiation median PSA was 30.1 ng/mL, 84%, 48% and 11% of patients had bone, nodal and visceral metastases. CSS from first-taxane were not significantly different between gMUT and non-carriers (NC) (16.9 vs 23.2 m, p > 0.05). However, in BRCA2 carriers was significantly shorter than in NC (13.1 vs 23.3 m, p = 0.026). Despite a trend to higher PSA response rates in gMUT compared to NC (n = 288, 63% vs 42%, p = 0.07, BRCA2 55%, p > 0.05), PFS were not significantly different between both groups (7.2 vs 7.8 m, p > 0.05), with a trend to shorter survival in BRCA2 carriers (4.5 vs 7.4 m, P = 0.11). Conclusions: These results suggest that DDR mutation carriers respond to taxanes with similar time to progression compared to NC, with the exception of BRCA2 carriers, who despite to the initial response to taxanes, presented worse survival outcomes. This highlights the need for close monitoring and novel therapies in this population. Clinical trial information: NCT03075735.