Abstract 189P
Background
The standard treatment of advanced HCC is immune checkpoint inhibitor (ICI) therapy. Metabolic dysfunction-associated steatotic liver disease (MASLD) appears to adversely affect the efficacy of ICI. No data on type 2 diabetes mellitus (T2DM)are avaible. Recently, the antidiabetic drug metformin has garnered attention for its possible antitumor and immunomodulatory properties, such as reduction of proinflammatory cytokines and CD8+ T cells activation during immunotherapy. The aim of our study was to investigate the role of metformin in patients treated with atezolizumab plus bevacizumab (A+B).
Methods
217 HCC patients (81.1% males, mean age 67.8) treated with A+B were enrolled from ARTE dataset. Clinical and radiological factors associated with patients’ response to therapy were used to stratify objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) by Kaplan- Meier methodology, followed by Log-rank test in multivariate analysis.
Results
In the T2DM population, the PFS based on Kaplan-Meier analysis, was significant between metformin vs others therapies (p=0.0025) and in particular when we divided in the three groups (p = 0.007), particularly the metformin group vs insulin group (median PFS 18.8 vs median PFS 4.8 months, p-value= 0.030), as well as in the metformin versus other therapeutic approaches (median PFS 2.9; p = 0.004), with a hazard ratio of 0.25 (95% CI 0.10-0.63, p=0,003). OS was also significantly different among metformin and other approaches (p = 0.013), with a hazard ratio of 0.30 (95% CI 0.11-0.78). In the multistep multivariate analysis among subgroups, the only factor significantly associated with disease progression (DCR) was metformin as a protective factor with an HR 0.32 (95 CI% 0.10-0.96), with a p=0.048.
Conclusions
For the first time, the multicentric ARTE dataset explore the synergic immunomodulant role of metformin with A+B on T2DM HCC patients showing a best response in term of DCR, PFS and OS. Specific randomized clinical trials are necessary to better understand the real immunological effects of metformin associated with ICIs in these settings of patients.
Legal entity responsible for the study
F. Tovoli.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.