A Phase 2 Randomized Study Comparing the Immune Effects of Palbociclib, Ribociclib, and Abemaciclib with Letrozole in Early ERHER2- Breast Cancer

What this Trial Is About

Researchers are evaluating and comparing the immune modulation effects of three FDA-approved CDK46 inhibitorspalbociclib, ribociclib, and abemaciclibcombined with letrozole as neoadjuvant treatment for early estrogen-receptor positive ERHER2-negative breast cancer. While all three inhibitors have shown progression-free survival benefits in advanced breast cancer, differences in overall survival might be influenced by their varying effects on the tumor microenvironment and immune system. This Phase 2 randomized study aims to provide a head-to-head comparison of these effects in the same trial. Participants will receive one of three treatment combinations palbociclib with letrozole, ribociclib with letrozole, or abemaciclib with letrozole. These CDK46 inhibitors are given alongside endocrine therapy before surgery over a 12-week period. Tissue, blood, and stool samples will be collected before treatment, two weeks after starting treatment, and after 12 weeks at surgery to analyze immune-related changes through RNA sequencing of breast tumors. During the study, researchers will monitor participants for immune response changes and adverse events. The primary outcome is the change in immune-related gene expression after treatment, assessed through RNA sequencing over an average follow-up of three years. Safety will be assessed over four months. Participants organ function and performance status will be evaluated before and during treatment to ensure safety and compliance with study procedures.

A Randomized Study Comparing the Immune Modulation Effect of Ribociclib, Palbociclib, and Abemaciclib in ER+/HER2- EBC