Therefore, to fill these gaps in the literature, this study aims to provide comprehensive cost-effectiveness analysis for the three FDA-approved CDK4/6 inhibitors —palbociclib, ribociclib, and abemaciclib in combination with letrozole (being the most commonly used combination with CDK4/6 inhibitors in Qatar (24)) in the first-line treatment for HR+/HER2- advanced breast cancer women. The gene discussed is CDK4; the disease is breast cancer.