Evaluating Metformin Addition to Paclitaxel/Carboplatin in Advanced and Recurrent Endometrial Cancer: Insights from an NRG Oncology/GOG Phase II/III Trial

Introduction

Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and represents a significant therapeutic challenge in advanced or recurrent settings. Standard first-line chemotherapy often comprises paclitaxel plus carboplatin (PC), which has demonstrated efficacy but remains associated with suboptimal long-term survival outcomes. Metformin, a widely used anti-diabetic medication, has demonstrated antitumor effects in preclinical studies through mechanisms including inhibition of the mTOR pathway and reduction of insulin/IGF signaling, which are implicated in endometrial carcinogenesis. The hypothesis that metformin could improve outcomes in EC has led to clinical investigation of its addition to chemotherapy regimens. This article critically appraises the randomized phase II/III study conducted by the NRG Oncology/GOG that evaluated the efficacy and safety of adding metformin to standard PC chemotherapy in patients with measurable stage III or IVA, stage IVB, or recurrent EC.

Study Background and Disease Burden