Letrozole, Abemaciclib, and Metformin Triplet Therapy Shows Robust Activity in ER-Positive Endometrioid Endometrial Cancer

Highlights

• The triplet combination of letrozole, abemaciclib, and metformin achieved an objective response rate (ORR) of 32% and a clinical benefit rate (CBR) of 60% in patients with ER-positive endometrioid endometrial cancer.
• The median progression-free survival (PFS) was 19.4 months, with a 6-month PFS rate of 69.8%.
• Significant activity was observed in tumors with CTNNB1 mutations, while no responses were seen in TP53-mutated cases.
• A novel pharmacokinetic finding revealed a more than 3-fold increase in metformin exposure when co-administered with letrozole and abemaciclib.

Introduction: The Rationale for Vertical Pathway Inhibition in Endometrial Cancer