Multicenter retrospective study of real-world effectiveness of PARP inhibitors after CDK4/6 inhibitor in BRCA-mutated HR+/HER2- aBC

PARP inhibitors (PARPi) are a standard-of care therapy for patients with HR-positive/HER2-negative advanced breast cancer (HR+ HER2- aBC) who harbor germline BRCA1/2 likely pathogenic or pathogenic variants (LP/PV). However, real-world efficacy of PARPi following tumor progression on first-line CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy ET) is not clear. A multicenter retrospective study in Italy evaluated this efficacy. Among 81 patients with HR+ HER2- aBC, 64 (79%) received first-line CDK4/6i plus ET. Considering the subsequent therapy after tumor progression, patients treated with PARP1 showed a significantly longer median real-world progression-free survival (11.8 months) compared to those receiving ET, monochemotherapy, or polychemotherapy. This benefit was confirmed in multivariable analysis. The authors conclude that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+ HER2- aBC.