CDK Inhibition in ER-Positive/HER2-Negative Metastatic Breast Cancer: Real-World Evidence of the Risk of Disease Progression on First-Line Treatment

Treatment with CDK4/6 inhibitors and endocrine therapy (ET) is standard first-line therapy for ER-positive/HER2-negative metastatic breast cancer. While abemaciclib, palbociclib, and ribociclib all have FDA and EMA approval, they appear to have distinct pharmacokinetic and inhibitory profiles. Aiming to clarify the natural history of disease with each CDK4/6 inhibitor, this single-site study was conducted to establish a risk prediction model for disease progression and to assess where there are differences in efficacy among the varying CDK4/6 inhibitors.

A total of 189 patients treated with ET plus abemaciclib, palbociclib, or ribociclib as frontline therapy for metastatic breast cancer in Virgin de Rocio Hospital between April 2014 and April 2021 were included. Patients were followed retrospectively for 3 years and studied according to their clinical characteristics using descriptive analysis. The risk of progression was studied by a transversal method using a univariate logistic regression model. Kaplan-Meier curves were used to estimate progression-free survival (PFS), and the Breslow test was used to estimate P value.

Overall survival was 30.03 months, with no clinically significant differences among the differing CDK4/6 inhibitors. In patients with visceral disease, overall PFS was 33.97 months. In patients with endocrine resistance, overall PFS was 19.75 months. Compared to abemaciclib, risk of progression was 2.36 (95% confidence interval [CI], 1.165-4.765; P = .017) and 2.50 (95% CI, 1.139-5.475; P = .022) times higher with palbociclib and ribociclib, respectively.

In this sample of patients with ER-positive/HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib as frontline therapy, while there were no clinically significant differences in PFS among the differing CDK4/6 inhibitors, the abemaciclib cohort trended towards a longer PFS. Investigators concluded that patients with ET seemed to benefit the most from abemaciclib; however, this is a single-site study and additional research will be needed to confirm whether first-line therapy with abemaciclib provides superior outcomes in PFS.

Source:

Cejuela M, Castilla MÁ, Benavent M, et al. Palbociclib, ribociclib, and abemaciclib in real-world data: risk of disease progression on first-line treatment of metastatic breast cancer. San Antonio Breast Cancer Symposium 2022. Abstract P3-01-13.