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
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...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
9 September 2025
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| In: |
European journal of cancer
Year: 2025, Volume: 227, Pages: 1-9 |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2025.115689 |
| Online Access: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.1016/j.ejca.2025.115689 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S095980492500471X 
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| Author Notes: | Laura L. Michel, Markus Wallwiener, Andreas Schneeweiss [und viele weitere] |
| Summary: | 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. |
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| Item Description: | Online verfügbar: 5. August 2025, Artikelversion: 7. August 2025 Gesehen am 22.01.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1879-0852 |
| DOI: | 10.1016/j.ejca.2025.115689 |