PARP inhibition with olaparib and talazoparib for HER2-negative advanced breast cancer - results from the prospective PRAEGNANT registry

  • Germline BRCA1 and BRCA2 mutations enable targeted therapies in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). The two poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors olaparib and talazoparib were introduced into clinical practice in 2018. Limited evidence about their routine clinical use highlights the importance of this analysis. We provide a real-world analysis for PARP-inhibitor use in ABC patients treated within the prospective German PRAEGNANT registry (NCT02338167). 152 patients with ABC receiving a PARP-inhibitor were included. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated for all patients using the Kaplan-Meier method. Subgroups (line of therapy, metastasis timing, hormone receptor (HR) status, treatment: olaparib, talazoparib, among others), germline BRCA1, BRCA2 and PALB2 mutations and adverse events (AEs) were analyzed. The median rwPFS was 6.2 months (95% CI,Germline BRCA1 and BRCA2 mutations enable targeted therapies in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). The two poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors olaparib and talazoparib were introduced into clinical practice in 2018. Limited evidence about their routine clinical use highlights the importance of this analysis. We provide a real-world analysis for PARP-inhibitor use in ABC patients treated within the prospective German PRAEGNANT registry (NCT02338167). 152 patients with ABC receiving a PARP-inhibitor were included. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated for all patients using the Kaplan-Meier method. Subgroups (line of therapy, metastasis timing, hormone receptor (HR) status, treatment: olaparib, talazoparib, among others), germline BRCA1, BRCA2 and PALB2 mutations and adverse events (AEs) were analyzed. The median rwPFS was 6.2 months (95% CI, 4.8-7.9) and the median rwOS was 17.1 months (95% CI, 14.4-22.3). Line of therapy, HR status and treatment (olaparib versus talazoparib) appeared to especially affect both rwPFS and rwOS. Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.show moreshow less

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Author:Manuel Hörner, Andreas Hartkopf, Nelson John, Philipp Ziegler, Lothar Häberle, Sabrina Uhrig, Chloë Goossens, Niklas Amann, Jan-Philipp Cieslik, Lara M. Tretschock, Dominik Dannehl, Thomas M. Deutsch, Moritz Dimpfl, Max Ehlert, Kathleen Eichstädt, Alexander Englisch, Melitta B. KöpkeORCiDGND, Annika Krückel, Theresa Link, Annika Müller, Kristin Reinhardt, Jonas Roth, Henning Schäffler, Lea Sych, Nikolas Tauber, Christian M. Tegeler, Catharina Wichmann, Maggie Banys-Paluchowski, Henriette Princk, Achim Rody, Sara Y. Brucker, Nina DitschORCiDGND, Johannes Ettl, Tanja Fehm, Carolin C. Hack, Peyman Hadji, Alexander Hein, Wolfgang W. Janni, Hans-Christian Kolberg, Diana Lüftner, Michael P. Lux, Volkmar Müller, Florin-Andrei Taran, Hans Tesch, Diethelm Wallwiener, Frederik Marmé, Stephan Seitz, Erik Belleville, Laura L. Michel, Markus Wallwiener, Peter A. Fasching, Andreas Schneeweiss, Christian Maurer
URN:urn:nbn:de:bvb:384-opus4-1297190
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/129719
ISSN:2374-4677OPAC
Parent Title (English):npj Breast Cancer
Publisher:Springer Science and Business Media LLC
Place of publication:Berlin
Type:Article
Language:English
Year of first Publication:2026
Publishing Institution:Universität Augsburg
Release Date:2026/04/30
Volume:12
Issue:1
First Page:60
DOI:https://doi.org/10.1038/s41523-026-00947-8
Institutes:Medizinische Fakultät
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Frauenheilkunde
Medizinische Fakultät / Professur für Operative und Konservative Senologie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung