Metformin exposure is associated with improved progression-free survival in diabetic patients after resection for early-stage non–small cell lung cancer

Abstract

ObjectiveThere are little clinical data assessing the antineoplastic effect of metformin in patients with non–small cell lung cancer. We hypothesized that in diabetic patients undergoing pulmonary resection for early-stage non–small cell lung cancer, metformin exposure is associated with improved survival. MethodsAn institutional database was used to identify patients with stage I or II non–small cell lung cancer who underwent pulmonary resection between 2004 and 2013. Patients were divided into 3 cohorts: type II diabetic patients with metformin exposure (cohort A, n = 81), type II diabetic patients without metformin exposure (cohort B, n = 57), and nondiabetic individuals (cohort C, n = 77). Univariate, multivariate, and propensity-matched analyses were performed to assess progression-free and overall survivals between groups. ResultsA total of 215 patients with stage I and II non–small cell lung cancer treated with surgical resection were identified for analysis with a median follow-up of 19.5 months. Patients in cohort A had lower T- and N-stage tumors than those in cohorts B or C. However, on multivariate analysis adjusting for age, gender, and T and N stage, progression-free survival was greater for cohort A than cohort B (hazard ratio [HR], 0.410; 95% confidence interval, 0.199-0.874; P = .022) or cohort C (HR, 0.415; 95% confidence interval, 0.201-0.887; P = .017). Likewise, when propensity-matched analyses were performed, cohort A demonstrated a trend toward improved progression-free survival compared with cohort B (P = .057; HR, 0.44; c-statistic = 0.832) and improved progression-free survival compared with cohort C (P = .02; HR, 0.41; c-statistic = 0.843). No differences were observed in overall survival. ConclusionsMetformin exposure in diabetic patients with early-stage non–small cell lung cancer may be associated with improved progression-free survival, but no effect was seen on overall survival. Further studies are warranted to evaluate if there is a therapeutic role for metformin in the treatment of non–small cell lung cancer.