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

Zeliha Birsin; Ali Kaan Güren; Vali Aliyev; Murad Guliyev; Seda Jeral; Selin Cebeci; Emir Çerme; Murat Günaltılı; Hamza Abbasov; Ebru Çiçek; Süheyla Atak; Murat Sarı; Nebi Serkan Demirci; Özkan Alan

doi:10.2147/BCTT.S598598

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

Breast Cancer (Dove Med Press). 2026 Apr 15:18:598598. doi: 10.2147/BCTT.S598598. eCollection 2026.

Authors

Affiliations

¹ Department of Medical Oncology, Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey.
² Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, Turkey.

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 neuropathy 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 differences in PFS or OS. Given their distinct toxicity profiles, treatment selection should be individualized according to patient characteristics and tolerability.

Keywords: CDK4/6 inhibitors; capecitabine; hormone receptor–positive breast cancer; paclitaxel; post-CDK4/6 inhibitor treatment; real-world study.