Use of Metformin and Survival in Patients with Hepatocellular Carcinoma (HCC) Undergoing Liver Directed Therapy: Analysis of a Nationwide Cancer Registry

Background Examine the association of metformin use and overall survival (OS) in patients with HCC undergoing image-guided liver-directed therapy (LDT): ablation, transarterial chemoembolization (TACE), or Yttrium-90 radioembolization (Y90 RE). Methods Using National Cancer Institute Surveillance, Epidemiology, and End Results registry and Medicare claims databases between 2007 and 2016, we identified patients ≥ 66 years who underwent LDT within 30 days of HCC diagnosis. Patients with liver transplant, surgical resection, and other malignancies were excluded. Metformin use was identified by at least two prescription claims within 6 months before LDT. OS was measured by time between first LDT and death or last Medicare observation. Comparisons were performed between both all and diabetic patients on and not on metformin. Results Of 2746 Medicare beneficiaries with HCC undergoing LDT, 1315 (47.9%) had diabetes or diabetes-related complications. Among all and diabetic patients, 433(15.8%) and 402 (30.6%) were on metformin respectively. Median OS was greater for patients on metformin (19.6 months, 95% CI 17.1–23.0) vs those not (16.0 months, 15.0–16.9; p = 0.0238). Patients on metformin had lower risk of death undergoing ablation (HR 0.70; 0.51–0.95; p = 0.0239) and TACE (HR 0.76, 0.66–0.87; p = 0.0001), but not Y90 RE (HR1.22, 0.89–1.69; p = 0.2231). Among diabetics, OS was greater for those on metformin vs those not (HR 0.77, 0.68–0.88; p < 0.0001). Diabetic patients on metformin had longer OS undergoing TACE (HR 0.71, 0.61–0.83; p < 0.0001), but not ablation (HR 0.74, 0.52–1.04; p = 0.0886) or Y90 RE (HR 1.26, 0.87–1.85; p = 0.2217). Conclusion Metformin use is associated with improved survival in HCC patients undergoing TACE and ablation.