The aim of this retrospective case-control study was to determine whether there is an association between metformin intake and survival of women with ovarian cancer. The cohort was composed of women with this cancer, who received (cases) and did not receive metformin (controls). In a 2-layer preliminary analysis, all 72 ovarian cancer cases were compared with 143 controls (the OC cohort). The subsequent definitive analysis showed that 61 of the 72 patients had epithelial ovarian cancer (EOC cohort). The definitive analysis matched the 61 EOC patients with 178 controls adjusting for the following primary variables: age at diagnosis (± 5 years), International Federation of Gynecology and Obstetrics stage, and residual disease after surgical cytoreduction. Kaplan-Meier estimates were used to compare prognostic variables and disease-specific survival using the log-rank test. Cox proportional hazards analysis was used to access the effect of risk factors on survival outcomes.
Preliminary analysis of the OC cohort showed better 5-year disease-specific survival for cases than controls (73% vs 44%; P = 0.002). With definitive analysis of the EOC cohort, there was no significant difference between cases and controls for the variables of age, International Federation of Gynecology and Obstetrics stage, optimal cytoreduction (residual disease), serous histology, and platinum chemotherapy (P > 0.05). However, cases had significantly better 5-year disease-specific survival than controls (67% vs 47%; P = 0.003). Multivariable analysis showed that metformin was an independent predictor of survival in patients with ovarian cancer after controlling for disease stage, grade, histology, type of chemotherapy, body mass index, and extent of surgical cytoreduction; the hazard ratio was 2.2, with a 95% confidence interval of 1.2–3.8 (P = 0.007).
These findings indicate that metformin intake is an independent predictive factor for survival in patients with ovarian cancer.
From the Department of Gynecologic Surgery (S.K., A.M., C.L., W.C.), Department of Biostatistics and Health Sciences Research (P.T.), and Department of Laboratory Medicine and Experimental Pathology (S.G., J.C., R.R., V.S.), Mayo Clinic College of Medicine, Rochester, MN