Capecitabine versus Paclitaxel After CDK4/6 Inhibitor Progression in Hormone Receptor- Positive, HER2-Negative Metastatic Breast Cancer: A Real-World Study


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Birsin Z., Guren A. K., Aliyev V., Guliyev M., Jeral S., Cebeci S., ...More

BREAST CANCER-TARGETS AND THERAPY, vol.18, 2026 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 18
  • Publication Date: 2026
  • Doi Number: 10.2147/bctt.s598598
  • Journal Name: BREAST CANCER-TARGETS AND THERAPY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
  • Open Archive Collection: AVESIS Open Access Collection
  • Istanbul University Affiliated: Yes

Abstract

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy represent the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. However, optimal chemotherapy selection after progression on CDK4/6i remains unclear. This study aimed to compare the clinical outcomes of capecitabine versus paclitaxel in a real-world post-CDK4/6i setting. Methods: This retrospective two-center study included HR+/HER2-metastatic breast cancer patients who experienced disease progression after CDK4/6i therapy and subsequently received either capecitabine or paclitaxel. Paclitaxel was administered at a dose of 80 mg/m2 weekly, while capecitabine was given at 1000-1250 mg/m2 twice daily on days 1-14 of a 21-day cycle. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analyses. Results: A total of 115 patients were included, of whom 68 (59%) received capecitabine and 47 (41%) received paclitaxel. Baseline clinicopathological characteristics were comparable between the two groups. The median follow-up was 48.3 months. Median PFS was 5.45 months in the capecitabine group and 6.53 months in the paclitaxel group (p = 0.622). Median OS was 42.2 and 43.1 months, respectively (p = 0.299). Treatment type was not independently associated either PFS or OS. Visceral metastasis after CDK4/6i progression independently predicted shorter PFS (HR 1.62, p = 0.042), whereas higher tumor grade was associated with inferior OS (HR 1.82, p = 0.018). Treatment-related toxicities differed between regimens: paclitaxel was predominantly associated with neuro-pathy and hematologic toxicity, whereas capecitabine was primarily associated with hand-foot syndrome and gastrointestinal toxicity. Conclusion: Capecitabine and paclitaxel demonstrated comparable efficacy after CDK4/6i progression, with no significant differ-ences in PFS or OS. Given their distinct toxicity profiles, treatment selection should be individualized according to patient characteristics and tolerability.