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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. Lim...

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Main Authors: Hörner, Manuel (Author) , Hartkopf, Andreas (Author) , John, Nelson (Author) , Ziegler, Philipp (Author) , Häberle, Lothar (Author) , Uhrig, Sabrina (Author) , Goossens, Chloë (Author) , Amann, Niklas (Author) , Cieslik, Jan-Philipp (Author) , Tretschock, Lara M. (Author) , Dannehl, Dominik (Author) , Deutsch, Thomas M. (Author) , Dimpfl, Moritz (Author) , Ehlert, Max (Author) , Eichstädt, Kathleen (Author) , Englisch, Alexander (Author) , Köpke, Melitta B. (Author) , Krückel, Annika (Author) , Link, Theresa (Author) , Müller, Annika (Author) , Reinhardt, Kristin (Author) , Roth, Jonas (Author) , Schäffler, Henning (Author) , Sych, Lea (Author) , Tauber, Nikolas (Author) , Tegeler, Christian M. (Author) , Wichmann, Catharina (Author) , Banys-Paluchowski, Maggie (Author) , Princk, Henriette (Author) , Rody, Achim (Author) , Brucker, Sara Y. (Author) , Ditsch, Nina (Author) , Ettl, Johannes (Author) , Fehm, Tanja (Author) , Hack, Carolin C. (Author) , Hadji, Peyman (Author) , Hein, Alexander (Author) , Janni, Wolfgang W. (Author) , Kolberg, Hans-Christian (Author) , Lüftner, Diana (Author) , Lux, Michael P. (Author) , Müller, Volkmar (Author) , Taran, Florin-Andrei (Author) , Tesch, Hans (Author) , Wallwiener, Diethelm (Author) , Marmé, Frederik (Author) , Seitz, Stephan (Author) , Belleville, Erik (Author) , Michel, Laura L. (Author) , Wallwiener, Markus (Author) , Fasching, Peter Andreas (Author) , Schneeweiss, Andreas (Author) , Maurer, Christian (Author)
Format: Article (Journal)
Language:English
Published: 11 April 2026
In: npj Breast cancer
Year: 2026, Volume: 12, Pages: 1-12
ISSN:2374-4677
DOI:10.1038/s41523-026-00947-8
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41523-026-00947-8
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41523-026-00947-8
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Author Notes: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. Köpke, 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 Ditsch, 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
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Summary: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.
Item Description:Gesehen am 04.05.2026
Physical Description:Online Resource
ISSN:2374-4677
DOI:10.1038/s41523-026-00947-8

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