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

Zeliha Birsin,1 Ali Kaan Güren,2 Vali Aliyev,1 Murad Guliyev,1 Seda Jeral,1 Selin Cebeci,1 Emir Çerme,1 Murat Günaltılı,1 Hamza Abbasov,1 Ebru Çiçek,1 Süheyla Atak,1 Murat Sarı,2 Nebi Serkan Demirci,1 Özkan Alan1 1Department of Medical Oncology, Faculty of Medicine, Istanbul University-Cerrahpaşa, Istanbul, Turkey; 2Department of Medical Oncology, Faculty of Medicine, Marmara University, Istanbul, TurkeyCorrespondence: Zeliha Birsin, Department of Medical Oncology, Faculty of Medicine, Istanbul University-Cerrahpaşa, Kocamustafapaşa Cd. No: 53, Fatih, Istanbul, 34098, Turkey, Tel +90 534 526 06 73, Email [email protected]: 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