Treatment Outcomes in Hormone Receptor-positive, HER2-negative Metastatic Breast Cancer Patients with and without Progression after Completion of Reimbursed Cyclin-dependent Kinase 4/6 Inhibitors in Taiwan: A Single-institution Experience

Background: Combining cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) with endocrine therapy is the standard first-line treatment for metastatic hormone receptor (HR)-positive, HER2-negative breast cancer. In Taiwan, it is estimated that nearly half of the patients completing 2 years of CDK4/6i treatment reimbursed by the National Health Insurance (NHI) program remain free of disease progression. Continuing CDK4/6i treatment beyond the reimbursement period imposes a financial burden on patients and makes it challenging for clinicians to determine optimal subsequent therapies, especially in resource-limited settings. This real-world, retrospective study aimed to evaluate the outcomes of HR-positive, HER2-negative metastatic breast cancer (MBC) patients who completed 19 months of CDK4/6i therapy, particularly those without disease progression. Materials and Methods: A total of 106 patients diagnosed with HR-positive, HER2-negative MBC and treated with CDK4/6is between September 1, 2015, and November 28, 2022, were enrolled for chart review and monitored until death or December 31, 2024. The exclusion criteria were loss to follow-up or unclear medication information ( n = 7), concurrent treatment for a second cancer ( n = 6), enrollment in clinical trials ( n = 3), switching treatment between two CDK4/6is ( n = 1), and HER2-positive disease after pathology revision ( n = 1). Survival analysis was performed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analysis was used to test the associations between clinical factors and survival using Cox proportional hazard models. All statistical tests were two-sided, and statistical significance was defined as P < 0.05. Results: Eighty-nine patients were eligible for evaluation, with a median follow-up time of 33.1 months. Fifty-three patients used CDK4/6is as first-line (1 L) therapy, and 35 used CDK4/6is as second or later lines (≥2 L). The median progression-free survival (PFS) was 22.1 months for the 1 L CDK4/6i users and 7.9 months for the ≥2 L CDK4/6i users. The median overall survival (OS) was 72.8 months for the 1 L CDK4/6i users and 28.8 months for the ≥2 L CDK4/6i users. The differences in both PFS and OS were statistically significant (log-rank test, P = 0.008 and 0.003, respectively). Among the 26 patients who received CDK4/6is for more than 19 months, we compared the “Lack of NHI reimbursement (NHIr)” group with the “Progression disease (PD) after 19 mo” group (patients who progressed after 19 months of 1 L CDK4/6i treatment). In the univariable model, the “Lack of NHIr” group was less likely to experience progression on post-CDK4/6i therapy compared to the “PD after 19 mo” group. After further adjustment, CDK4/6i type (ribociclib), proton pump inhibitor use, and post-CDK treatment were independent prognostic factors associated with PFS2 events, whereas NHIr status was not significantly associated with subsequent treatment outcomes. Conclusion: In this single-institution retrospective study, PFS and OS in the patients who received CDK4/6i treatment were comparable to those reported in pivotal phase 3 clinical trials, both in first-line and later-line settings. In terms of disease progression on next-line therapy in the patients who used CDK4/6is >19 months, ribociclib showed better PFS2, compared to palbociclib or abemaciclib. Due to the limited sample size, factors such as age, the presence of more than two metastatic sites, and lack of reimbursement were not significantly correlated with poorer outcomes.