Comparative effectiveness of first-line ribociclib plus aromatase inhibitor versus palbociclib plus aromatase inhibitor in HR+/HER2− metastatic breast cancer: A global real-world evidence study.
Shankar Biswas, Yashasvi Srivastava, Ayman Hamadttu45
Background:
CDK4/6 inhibitors combined with aromatase inhibitors (AIs) are the standard first-line therapy for HR+/HER2− metastatic breast cancer (mBC). While ribociclib demonstrated significant overall survival (OS) benefit in MONALEESA-2 (HR 0.76; p=0.008), palbociclib did not in PALOMA-2 (HR 0.96; p=0.34). No head-to-head randomized trial exists. Real-world comparative effectiveness data remain limited and inconsistent.
Methods:
Using the TriNetX Global Collaborative Network (171 healthcare organizations), we identified patients with HR+/HER2− mBC initiating first-line ribociclib+AI (Cohort A) or palbociclib+AI (Cohort B), with AI commenced within 30 days of CDK4/6i. 1:1 propensity score matching (PSM) balanced demographics, metastatic sites, modified Charlson comorbidities, and laboratory values. Outcomes included OS, real-world time to next treatment (rwTTNT), and safety. Cox proportional hazards, Kaplan-Meier, and risk analyses were performed.
Results:
Before matching, 742 ribociclib and 1,818 palbociclib patients were identified; after PSM, 702 per cohort were retained with well-balanced covariates (all standardized differences <0.10). Median follow-up was 393 days (ribociclib) vs 692 days (palbociclib). Key outcomes are shown in the Table. Ribociclib was associated with significantly lower mortality (median OS 2,165 vs 1,631 days). ILD risk was significantly lower with ribociclib (risk ratio 0.482; p=0.025), as was VTE (risk ratio 0.545; p=0.017). Arrhythmia showed a borderline higher rate with ribociclib, consistent with known QTc prolongation risk.
Conclusions:
In this large global real-world study, first-line ribociclib+AI was associated with statistically significant OS advantage over palbociclib+AI in HR+/HER2− mBC, with a comparable safety profile. These findings complement indirect comparisons from MONALEESA-2 and PALOMA-2 and support differential OS benefit between CDK4/6 inhibitors in real-world practice.
Outcomes.