BREAST CANCER: TARGETS AND THERAPY, cilt.Volume 18, ss.1-13, 2026 (SCI-Expanded, Scopus)
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, post-CDK4/6 inhibitor treatment, hormone receptor–positive breast cancer, capecitabine, paclitaxel, real-world study