Strategies to overcome endocrine resistance in HR+/HER2- metastatic breast cancer: a real-world data

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy are the standard of care for HR+/HER2- metastatic breast cancer (mBC). However, the comparative effectiveness of different agents within this class in real-world clinical practice (RWCP) is insufficiently studied, particularly in the Russian population. Objective. To analyze the efficacy and safety of various iCDK4/6 (palbociclib and ribociclib) in real clinical practice at the St. Petersburg City Clinical Oncology Dispensary. Material and methods. A single-center retrospective cohort study with elements of prospective data collection was conducted. The analysis included 815 patients who received CDK4/6is in combination with endocrine therapy between January 2019 and March 2023. Progression-free survival (PFS), objective response rate, and univariate and multivariate analyses of various clinical and morphological factors influencing treatment efficacy were assessed. Propensity score matching (PSM) was used to minimize systematic bias when comparing palbociclib and ribociclib. Results. The median PFS in the overall population was 24.0 months (95% CI 20.2—27.8). In multivariate analysis, the presence of liver metastases (HR 1.95; p<0.001) and administration of CDK4/6i therapy in the second and subsequent lines (HR 1.34; p<0.001) were independent unfavorable prognostic factors. After PSM (n=174), the palbociclib and ribociclib groups were comparable in baseline characteristics; median PFS was 22 and 24 months, respectively (log-rank p=0.808). The objective response rate was higher in the palbociclib group (37.9% vs. 9.2%; p<0.001). Conclusion. In real-world clinical practice, CDK4/6 inhibitors demonstrate high effectiveness comparable to the results of registration trials. Palbociclib and ribociclib have similar PFS outcomes. Key factors worsening prognosis are visceral metastases (especially liver involvement) and later lines of therapy.