Molecular and metabolic differences of treatment responders versus nonresponders in a phase 0 clinical trial of metformin in endometrial cancer

Abstract

In univariate analysis, 6-month δ-BMI change was significantly associated with DFS and OS (both, P b .001): 5-year rates, ≥15% δ-BMI loss (33.5% and 59.1%), 7.5% to 14.9% loss (67.3% and 70.0%), b7.5% loss (87.8% and 95.7%), b7.5% gain (87.2% and 90.3%), 7.5% to 14.9% gain (64.6% and 67.6%), and ≥15% gain (32.5% and 66.7%). In multivariable analysis controlling for age, ethnicity, baseline BMI, histology, grade, stage, chemotherapy, and radiotherapy, 6-month δ-BMI change remained an independent prognostic factor for DFS and OS (all, P b .05): adjusted-HRs, ≥15% δ-BMI loss (3.35 and 5.39), 7.5% to 14.9% loss (2.35 and 4.19), 7.5% to 14.9% gain 2.58 and 3.33), and ≥15% gain (2.50 and 3.45) compared with b7.5% loss. (See Fig. 1.) Similar findings were observed at the 1-year time point (P b .05). Baseline BMI was not associated with survival outcome (P N .05). Conclusions: Our results demonstrated that endometrial cancer patients continued to gain weight after hysterectomy and posttreatment weight change had a bidirectional effect on survival outcome.