Platinum-based chemotherapy and PARP inhibitors for patients with a germline BRCA pathogenic variant and advanced breast cancer (LATER-BC): retrospective multicentric analysis of post-progression treatments

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Introduction: Patients with breast cancer (BC) harbouring a germinal BRCA pathogenic variant (gBRCA-PV) may have an enhanced sensitivity to platinum-based chemotherapy (PBC) and PARP inhibitors (PARPi). As reported in ovarian cancer, however, sensitivity and resistance to these treatments could partially overlap. In patients with a gBRCA-PV and advanced BC (aBC), it remains unclear whether prior exposure to PARPi/PBC affects tumour response to subsequent PBC/PARPi, respectively. Methods: We conducted a retrospective, multicentric study to investigate the clinical benefit of post-PBC PARPi and vice versa in patients with a gBRCA-PV and aBC. Patients included had received (neo)adjuvant PBC and then PARPi in advanced setting (group 1), PBC followed by PARPi (group 2) or PARPi followed by PBC (group 3), both in advanced setting. We reported median progression-free survival (mPFS) and disease control rate (DCR) in each group. Results: A total of 67 patients from six centres were included. PARPi-mPFS in advanced setting was 6.1 months in patients in group 1 (N = 12), while PARPi-DCR was 67%. In group 2 (N = 36), PARPi-mPFS was 3.4 months and PARPi-DCR was 64%. Age < 65 years and platinum-free interval (PFI) > 6 months were associated with longer PARPi-PFS; previous PBC-PFS > 6 months and PBC in first to second line were associated with longer PARPi-DCR. Patients in group 3 (N = 21) reported a PBC-mPFS of 1.8 months and a PBC-DCR of 14%. PARPi-PFS ≥ 9 months and PARPi-FI ≥ 6 months were associated with better PBC-DCR. Conclusions: Sensitivity and resistance to PARPi and PBC partially overlap in patients with a gBRCA-PV and aBC. Evidence of PARPi activity emerged in patients who progressed on previous PBC.

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