Real-world effectiveness of PARP inhibitors after CDK4/6 inhibitor therapy in BRCA-mutated HR-positive/HER2-negative advanced breast cancer
Year: 2025
Type: article
Study design: Observational Study
Abstract: Poly(ADP-ribose) polymerase inhibitors (PARPi) are established as standard-of-care therapy for patients with hormone receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC) who harbor germline BRCA1/2 likely pathogenic or pathogenic variants (LP/PV). However, the real-world efficacy of PARPi following tumor progression on first-line (1 L) cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) remains inadequately explored. In this cohort of 81 patients with HR+/HER2- aBC harboring germline BRCA LP/PV, 64 (79%) received 1 L treatment with CDK4/6i plus ET. Considering the subsequent therapy administered after tumor progression on 1 L CDK4/6i, patients treated with PARPi showed a significantly longer median real-world PFS (11.8 months) compared to those receiving ET, monochemotherapy, or polychemotherapy. This benefit was confirmed in a multivariable analysis, supporting PARPi as the preferred option in eligible patients. Our findings suggest that PARPi should be prioritized in the post-CDK4/6i treatment sequence for BRCA LP/PV carriers with HR+/HER2 aBC and highlight the critical role of germline BRCA testing.
Source: npj Breast Cancer
Authors: Emma Zattarin, Antonio Marra, Antonella Palazzo, Gaia Griguolo, Claudio Vernieri, Julian Etessami, Letizia Pontolillo, Giusy Landa, Arianna Daneri, Matteo De Monte, Riccardo Cuoghi Costantini, Elena Tenedini, Ornella Ponzoni, Maria Grazia Razeti, Caterina Sposetti, Elena Barbieri, Martina Manni, Federica Caggia, Laura Cortesi, Giuseppe Curigliano, Emilio Bria, Massimo Dominici, Valentina Guarneri, Matteo Lambertini, Angela Toss
Institutions: University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, European Institute of Oncology, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, University of Padua, Istituto Oncologico Veneto, University of Milan, Fondazione IRCCS Istituto Nazionale dei Tumori, Weill Cornell Medicine, Ospedale Policlinico San Martino, Harvard University, Dana-Farber Cancer Institute, Azienda Sanitaria Unità Locale di Reggio Emilia, Università Cattolica del Sacro Cuore, University of Genoa
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
OpenAlex ID: W4417321390