Impact of metformin on clinical outcomes in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors

Background and Aims Non-alcoholic steatohepatitis (NASH) is a common cause of hepatocellular carcinoma (HCC) worldwide. Emerging data suggests NASH-induced HCC could be associated with less response to immune checkpoint inhibitor (ICI)-based therapy. Metformin has been improved outcomes in cancers like melanoma treated ICIs, but its impact on not well defined. The purpose this study was examine the effect metformin clinical patients advanced ICIs. Methods We retrospectively analysed ICIs first later-line settings between 2015 2021. primary endpoints were overall survival (OS), progression-free (PFS), objective rate (ORR) as assessed according Response Evaluation Criteria Solid Tumours (RECIST) version 1.1. Patients stratified based their usage metformin. Results Our included 18 group 93 non-metformin group. most causes viral hepatitis (52%), NASH (29%), alcohol (8%). ORR 5.6% vs 22.6% (P = .0987). Median OS 10.8 months versus 45.9 (HR 1.99, 95% CI 0.95–4.21, P .065) median PFS 2.5 6.6 .077) groups, respectively. Regardless usage, significantly worse poor ECOG performance status, aetiology NASH, MELD score 10–23, AFP >= 400, use later lines Conclusions trend, although statistically significant, toward ORR,