Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer

Michel LL, Ziegler P, Kreis P, Hartkopf AD, Wallwiener M, Häberle L, John N, Kolberg HC, Hadji P, Tesch H, Ettl J, Lüftner D, Müller V, Belleville E, Wimberger P, Enzinger HM, Hübner H, Uhrig S, Hack C, Krabisch P, Fasching P, Wuerstlein R, Untch M, Ditsch N, Hein A, Janni W, Taran FA, Lux MP, Wallwiener D, Brucker SY, Fehm TN, Schneeweiss A, Goossens C, Engler T (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 227

Article Number: 115689

DOI: 10.1016/j.ejca.2025.115689

Abstract

Introduction: Whereas CDK4/6 inhibitors (CDK4/6i) are the standard first-line therapy for patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer, guidelines on treatment options after progression on CDK4/6i are more diverse. Chemotherapy is recommended if a patient develops endocrine resistance or experiences a visceral crisis. However, the impact of the choice of chemotherapy remains unknown. Methods: HRpos/HER2neg patients who received first-line CDK4/6i, followed by second-line chemotherapy (N = 215) were selected from the prospective PRAEGNANT registry (NCT02338167). Cox regression analyses were used to evaluate the correlation between the choice of chemotherapy (capecitabine monotherapy, capecitabine + bevacizumab, taxane monotherapy, taxane + bevacizumab, anthracycline, other chemotherapeutics) and progression-free survival (PFS) and overall survival (OS). Results: Patients who received second-line chemotherapy mostly had high-grade tumors (G2: 62.3 %, G3: 33.3 %), visceral metastases (62.3 %) and developed metastatic disease following a primary breast cancer diagnosis (73.8 %). Capecitabine was the most common regimen (25.1 %), followed by taxane + bevacizumab (17.2 %). When adjusting for other prognostic factors (age, BMI, grading, ECOG, metastasis group and time to metastases), the choice of chemotherapy did not influence PFS (p = 0.16) nor OS (p = 0.47). Adjusted hazard ratios for PFS were lowest in regimens with bevacizumab (capecitabine as reference; capecitabine + bevacizumab: 0.53 (95 %CI: 0.29, 0.97); taxane + bevacizumab: 0.64 (95 %CI 0.35, 1.15)). Conclusion: Although the choice of chemotherapy post-CDK4/6i did not significantly affect PFS or OS, combinations with bevacizumab may have some benefit. Nevertheless, considering side effects may be most important when choosing the type of second-line chemotherapy.

Authors with CRIS profile

Involved external institutions

HELIOS Kliniken Germany (DE) Universität Augsburg Germany (DE) St. Josefs-Krankenhaus Salzkotten Germany (DE) Universitätsklinikum Heidelberg Germany (DE) Universitätsklinikum Tübingen Germany (DE) Agaplesion Markus Krankenhaus Germany (DE) Klinikum rechts der Isar Germany (DE) Medizinische Hochschule Brandenburg "Theodor Fontane" / Brandenburg Medical School "Theodor Fontane" Germany (DE) Martin-Luther-Universität Halle-Wittenberg (MLU) Germany (DE) Marienhospital Bottrop Germany (DE) Frankfurter Hormon und Osteoporosezentrum Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) ClinSol GmbH & Co.KG Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Sozialstiftung Bamberg Germany (DE) Technische Universität Dresden Germany (DE) Klinikum der Universität München Germany (DE) Städtische Kliniken Esslingen Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Köln Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE)

How to cite

APA:

Michel, L.L., Ziegler, P., Kreis, P., Hartkopf, A.D., Wallwiener, M., Häberle, L.,... Engler, T. (2025). Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer. European Journal of Cancer, 227. https://doi.org/10.1016/j.ejca.2025.115689

MLA:

Michel, Laura L., et al. "Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer." European Journal of Cancer 227 (2025).

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