CDK4/6 Inhibitors and Endocrine Therapy in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Multicenter Real-World Cohort

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy are standard treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, but Latin American patients were underrepresented in the pivotal trials, and real-world data from public health systems remain scarce. We aimed to describe the effectiveness and safety of these agents in the Costa Rican public health system and to explore differences between palbociclib and ribociclib. Methods: We conducted a retrospective, multicenter cohort study of adults with HR-positive/HER2-negative metastatic breast cancer who started palbociclib or ribociclib plus endocrine therapy in first or later lines of therapy at four hospitals of the Costa Rican Social Security Fund (treatment indicated 2017–2021). Progression-free survival (PFS) and overall survival (OS), measured from CDK4/6 inhibitor initiation, were estimated with the Kaplan–Meier method. The inhibitor comparison was exploratory and was adjusted with a multivariable Cox model with covariates selected a priori and with inverse probability of treatment weighting. Dose reduction was analyzed as a time-dependent covariate and with landmark analyses. Results: Of 234 patients identified, 14 died or progressed before treatment could start; 220 patients were analyzed (palbociclib 65.5%, ribociclib 34.5%; first-line 60.9%). At a median follow-up of 45.1 months, median PFS was 19.4 months and median OS was 29.1 months (first-line: 24.4 and 39.7 months; second or later line: 15.0 and 23.3 months). PFS and OS did not differ significantly between inhibitors (adjusted hazard ratio (HR) for ribociclib versus palbociclib: PFS 0.89, 95% confidence interval (CI) 0.62–1.26; OS 0.92, 95% CI 0.63–1.36). Eastern Cooperative Oncology Group (ECOG) performance status 1 and the second or later line of therapy were independently associated with shorter PFS and OS. Grade 3/4 adverse events were recorded in 20.5% of patients (grade 3/4 neutropenia 18.6%). Dose reduction, required in 15.9% of patients and analyzed as a time-dependent covariate, was not associated with PFS (adjusted HR 1.04, 95% CI 0.67–1.61) or OS (adjusted HR 0.77, 95% CI 0.46–1.30). Conclusions: In this national public-system cohort, CDK4/6 inhibitors were deliverable with a manageable, predominantly hematological toxicity profile. PFS was in the range reported in trials and real-world series, whereas OS was shorter than in the registration trials and in other large real-world cohorts, particularly beyond first line. No significant difference was observed between ribociclib and palbociclib after adjustment, and dose reduction did not appear to compromise effectiveness.