1099 Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are widely used in hormone receptor-positive (HR+) / HER2-negative (HER2-) metastatic breast cancer, yet real-world differences in survival and clinically relevant toxicities across agents remain unclear. We performed a propensity score-matched (PSM) sensitivity analysis comparing ribociclib and palbociclib, focusing on mortality and selected safety endpoints. Methods: Using the TrinetX database, a federated real-world data network, adult patients with HR+/HER2- metastatic breast cancer treated with ribociclib (cohort 1) or palbociclib (cohort 2) were identified. 1:1 propensity score matching was performed on more than 20 baseline characteristics. Outcomes were evaluated using (1) risk analyses excluding patients with the outcome prior to the time window and (2) Kaplan-Meier time-to-event analyses with hazard ratios (HRs). Endpoints included all-cause mortality, prolonged QT, cardiac arrest, liver injury, hospital admission, and emergency department (ED) visits. Results: Patient counts were 2,819 vs 11,871 before matching and 2,696 vs 2,696 after matching. In the matched cohorts, ribociclib was associated with significantly lower all-cause mortality compared with palbociclib (HR 0.65, 95% CI 0.552-0.758, p <0.0001). No statistically significant differences were observed in major cardiovascular safety outcomes. Specifically, rates of cardiac arrest were comparable between groups (HR 0.76, 95% CI 0.384-1.505, p =0.43), as were rates of long QT syndrome (HR 0.837, 95% CI 0.425-1.648, p =0.61). With respect to hepatic and healthcare utilization outcomes, liver injury occurred numerically more often in the ribociclib group, but this difference did not reach statistical significance (HR 1.209, 95% CI 0.896-1.632, p =0.21). Ribociclib was associated with numerically lower rates of hospitalization (HR 0.845, 95% CI 0.700-1.021, p =0.08) and ED visits (HR 0.82, 95% CI 0.659-1.02, p =0.07), though neither outcome met conventional thresholds for statistical significance. Conclusions: In this PSM analysis of HR+/HER2- metastatic breast cancer, ribociclib was associated with significantly lower all-cause mortality compared with palbociclib. Rates of hospitalization, ED visits, prolonged QT, and cardiac arrest were not significantly different. These real-world findings support clinically meaningful heterogeneity across CDK4/6 inhibitors and highlight the importance of individualized agent selection, balancing survival, hepatic toxicity, and healthcare utilization.
Abbas et al. (Wed,) studied this question.