To evaluate the efficacy and safety of three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (abemaciclib, dalpiciclib, and ribociclib) currently available in China for patients with hormone receptor (HR)-positive/HER-2-negative (HR+/HER-2-) breast cancer.

Clinical data of 337 HR+/HER-2- breast cancer patients who received CDK4/6 inhibitor therapy at four hospitals in Jilin Province (the First, Second, and Third Bethune Hospitals of Jilin University, and Jilin Provincial Cancer Hospital) from March 2021 to December 2025 were retrospectively collected. Patients were stratified by clinical stage into the early-stage cohort (stage Ⅱ–Ⅲ, n=160) and the advanced-stage cohort (stage Ⅳ, n=177), and by different CDK4/6 inhibitors received, into the abemaciclib group (n=82), dalpiciclib group (n=119), and ribociclib group (n=136). Survival curves were plotted using the Kaplan-Meier method and intergroup comparisons were performed using the log-rank test. Analyze the occurrence of adverse events (AE) in each group of patients, and the factors influencing AE were analyzed using multivariate logistic regression.

All patients were followed up until January 1, 2026. In the early-stage cohort, the 3-year invasive disease-free survival rates for the abemaciclib, dalpiciclib, and ribociclib groups were 83.2%, 87.4%, and 100%, respectively，indicating a significant difference across the three groups (χ²=7. 338，P=0. 025). In the advanced-stage cohort, the median progression-free survival in the three groups was 32.0 months (95%CI: 25.3–NA), 36.7 months (95%CI: 30.4–NA), and 24.2 months (95%CI: 22.2–NA), respectively, with no statistically significant difference (χ²=3. 292，P=0. 193). The overall incidences of AE in the early-stage cohort were 97.2% (35/36), 96.8% (30/31), and 97.8% (91/93) for the abemaciclib, dalpiciclib, and ribociclib groups, respectively; in the advanced-stage cohort, the corresponding incidences were 95.7% (44/46), 97.7% (86/88), and 97.7%(42/43), respectively, with no statistically significant difference in both cohorts (χ²=0.125, 0.525; P=0.939, 0.769). The AE profiles differed substantially among the three CDK4/6 inhibitors. The abemaciclib group showed the highest incidences of anemia [early-stage cohort: 55.6% (20/36); advanced-stage cohort: 69.6% (32/46)], diarrhea [early-stage cohort: 88.9% (32/36); advanced-stage cohort: 89.1% (41/46)], interstitial lung disease (ILD) [early-stage cohort: 5.6% (2/36); advanced-stage cohort: 8.7% (4/46)], and venous thromboembolism (VTE) [early-stage cohort: 2.8% (1/36); advanced-stage cohort: 6.5% (3/46)]. The dalpiciclib group had the highest incidences of neutropenia [early-stage cohort: 93.5% (29/31); advanced-stage cohort: 94.3% (83/88)] and leukopenia [early-stage cohort: 93.5% (29/31); advanced-stage cohort: 95.4% (84/88)]. The ribociclib group showed the highest incidences of elevated alanine aminotransferase (ALT) /aspartate aminotransferase (AST) [early-stage cohort: 34.4% (32/93)/36.6% (34/93); advanced-stage cohort: 39.5% (17/43) for both] and QTc interval prolongation [early-stage cohort: 1.1% (1/93); advanced-stage cohort: 2.3% (1/43)]. Multivariate logistic regression analysis revealed that drug type was an independent risk factor for grade ≥3 AEs. In the early-stage cohort, both abemaciclib (OR=2.847, 95%CI: 1.270–6.384, P=0.011) and dalpiciclib group (OR=7.047, 95%CI: 2.776–17.889, P<0.001) had a higher risk of grade ≥3 AEs compared with ribociclib group. In the advanced-stage cohort, dalpiciclib group (OR=4.670, 95%CI: 2.054–10.618, P<0.001) had a significantly higher risk of grade ≥3 AEs than abemaciclib group, while the risk in ribociclib group was not significantly different from that in the abemaciclib group (OR=2.365, 95%CI: 0.948–5.900, P=0.065).

All three CDK4/6 inhibitors demonstrated favorable efficacy and acceptable safety in patients with HR+/HER-2- breast cancer; however, their AE profiles and risk of grade ≥3 AEs differ significantly.