Cyclin inhibitors for breast cancer: a comparative real world data analysis

Abstract

Objective: This study aimed to evaluate the impact of different cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6) as
first line therapy on median overall survival (mOS) in a contemporary real-world setting. Methods: Data from TriNetX (a
global dataset of electronic medical records of patients from 111 healthcare organizations) were analyzed and queried for
patients with specific terms between 2004–2024. A propensity score matching analysis balanced the cohort. Ribociclib (Rib),
palbociclib (Palb), and abemaciclib (Abem) were compared using a 2x2 group selection method. Analysis 1 compared Rib
vs. Abem; Analysis 2 compared Rib vs. Palb; and Analysis 3 compared Palb vs. Abem. The mOS was evaluated with the
Kaplan–Meier method. Statistical comparison was performed with a stratified log-rank test. Results: No difference in
risk for death was identified in Analysis 1 (271 patients in each arm), with a not reached mOS for both cohorts (5 years;
OS 61.82% vs. 53.66%, ꭓ²=0.03; p=0.863; hazard ratio [HR] 0.964; 95% confidence interval [CI] 0.634–1.467). Analysis 2 (980
patients in each arm) revealed a statistically significant increased risk of death when receiving Palb over Rib (risk ratio [RR]
2.42; 95%CI -0.202–0.280; p≤0.0001) with mOS of 1,286 vs. 1,946 days (ꭓ²=15.447; p<0.0001; HR 1.441; 95%CI 1,200–1,731).
Analysis 3 (318 patients in each arm), revealed a statistically significant increased risk of death when receiving Palb over
Rib (RR 2.47; 95%CI -0.231–0.372; p≤0.0001) with mOS of 1,124 vs. 1,706 days (ꭓ²=9.025; p<0.003; HR 1.56, 95%CI 1,165–2,091).
Conclusion: Our study revealed that patients treated with Palb instead of Rib or Abem achieved a lower mOS with an
increased risk of death from breast cancer. Additionally, when comparing Rib to Abem, despite a percentage trend favoring Rib, no difference was found in the overall survival analysis for the risk of death from breast cancer.