Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial

Hörner M, Tretschock LM, John N, Ziegler P, Häberle L, Uhrig S, Goossens C, Amann N, Cieslik JP, Dannehl D, Deutsch TM, Dimpfl M, Ehlert M, Eichstädt K, Englisch A, Köpke MB, Krückel A, Link T, Müller A, Reinhardt K, Roth J, Schäffler H, Sych L, Tegeler CM, Wichmann C, Banys-Paluchowski M, Princk H, Rody A, Brucker SY, Ditsch N, Ettl J, Fehm T, Hack C, Hadji P, Hein A, Janni WW, Kolberg HC, Lüftner D, Lux MP, Müller V, Schneeweiss A, Taran FA, Tesch H, Wallwiener D, Marmé F, Seitz S, Belleville E, Hartkopf A, Michel LL, Wallwiener M, Fasching P, Tauber N (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Breast Cancer Research and Treatment Springer Nature

Book Volume: 217

Article Number: 9

Journal Issue: 1

DOI: 10.1007/s10549-026-07939-z

Abstract

Purpose: Mutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant was the first approved PI3K inhibitor and was introduced in clinical practice in 2019. A lack of evidence for the use of alpelisib in the context of current treatment options like cyclin-dependent 4/6 inhibitor (CDK4/6i), highlights the importance of this analysis. We provide a real-world analysis of the use of alpelisib with the prospective German PRAEGNANT registry (NCT02338167). Methods: 57 patients with advanced breast cancer receiving alpelisib and fulvestrant were identified. 55 Patients had received prior CDK4/6i therapy. Progression-free survival (PFS) and overall survival (OS) were calculated for all patients, and stratified according CDK4/6i pre-treatment, using the Kaplan–Meier method. Subgroups (age, line of therapy, concomitant disease among others), somatic PIK3CA mutations, reasons for discontinuation and adverse events (AEs) were analyzed. Results: The median PFS was 5.0 (95% confidence interval [CI], 3.1–9.4) months, and the median OS was 20.1 (95% CI, 14.6–30.8) months. Line of therapy and concomitant diseases appeared to affect PFS, while the line of therapy and preexisting diabetes influenced OS. However, subgroups were too small for statistical testing. Discontinuation was mainly due to tumor progression (56.1%). Hyperglycemia, rash and diarrhea were the most documented AEs. Conclusion: This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.

Authors with CRIS profile

Manuel Hörner Department of Obstetrics and Gynaecology Lothar Häberle Department of Obstetrics and Gynaecology Sabrina Uhrig Department of Obstetrics and Gynaecology Niklas Amann Department of Obstetrics and Gynaecology Annika Krückel Department of Obstetrics and Gynaecology Carolin Hack Department of Obstetrics and Gynaecology Peter Fasching Department of Obstetrics and Gynaecology

Involved external institutions

Universitätsklinikum Heidelberg DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE) Universitätsklinikum Mannheim / University Medical Centre Mannheim (Universitätsmedizin Mannheim) DE Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Universitätsklinikum Halle (Saale) DE Germany (DE) Universitätsklinikum Augsburg DE Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE) Universitätsklinikum Ulm DE Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Klinikum rechts der Isar DE Germany (DE) Marienhospital Bottrop DE Germany (DE) Medizinische Hochschule Brandenburg "Theodor Fontane" / Brandenburg Medical School "Theodor Fontane" DE Germany (DE) St. Vincenz-Kliniken GmbH DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Agaplesion Markus Krankenhaus DE Germany (DE) ClinSol GmbH & Co.KG DE Germany (DE) Frankfurter Hormon und Osteoporosezentrum DE Germany (DE) Städtische Kliniken Esslingen DE Germany (DE)

How to cite

APA:

Hörner, M., Tretschock, L.M., John, N., Ziegler, P., Häberle, L., Uhrig, S.,... Tauber, N. (2026). Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial. Breast Cancer Research and Treatment, 217(1). https://doi.org/10.1007/s10549-026-07939-z

MLA:

Hörner, Manuel, et al. "Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial." Breast Cancer Research and Treatment 217.1 (2026).

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