Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential a...Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control.This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus(T2DM)receiving A+B therapy.Methods:This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE(Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma)dataset across 18 Italian centres(May 2020-January 2024).We evaluated objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and time to progression(TTP)using Cox regression analysis and Inverse Probability of Treatment Weighting(IPTW)to address confounding.Results:Among 523 patients,341(65.2%)did not have diabetes and 182(34.8%)had T2DM.In the overall population,metformin showed no significant benefit for PFS(HR=1.15,95%CI[0.88-1.50],p=0.316)or OS(HR=1.28,95%CI[0.94-1.74],p=0.124).In the subgroup with T2DM(N=180),metformin showed no significant benefit for PFS(HR=1.41,95%CI[0.97-2.05],p=0.069),OS(HR=1.23,95%CI[0.81-1.86],p=0.333),or TTP(HR=0.82,95%CI[0.53-1.26],p=0.363).IPTW analysis confirmed these negative findings.Conclusion:This study found no evidence of improved outcomes with metformin use in patients with HCC in particular with T2DM receiving A+B therapy.Routine metformin use should not be expected to enhance A+B efficacy based on current evidence.展开更多
文摘Objectives:The combination of atezolizumab plus bevacizumab(A+B)represents one of the standards first-line treatments for unresectable hepatocellular carcinoma(HCC).Metformin has garnered attention for its potential antitumour and immunomodulatory properties beyond glycaemic control.This study aimed to assess metformin’s impact in patients with type 2 diabetes mellitus(T2DM)receiving A+B therapy.Methods:This retrospective analysis of a prospectively-maintained multicentre database included 523 patients with HCC treated with A+B from the ARTE(Atezolizumab-bevacizumab Real-life Experience for Treatment of Hepatocellular Carcinoma)dataset across 18 Italian centres(May 2020-January 2024).We evaluated objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and time to progression(TTP)using Cox regression analysis and Inverse Probability of Treatment Weighting(IPTW)to address confounding.Results:Among 523 patients,341(65.2%)did not have diabetes and 182(34.8%)had T2DM.In the overall population,metformin showed no significant benefit for PFS(HR=1.15,95%CI[0.88-1.50],p=0.316)or OS(HR=1.28,95%CI[0.94-1.74],p=0.124).In the subgroup with T2DM(N=180),metformin showed no significant benefit for PFS(HR=1.41,95%CI[0.97-2.05],p=0.069),OS(HR=1.23,95%CI[0.81-1.86],p=0.333),or TTP(HR=0.82,95%CI[0.53-1.26],p=0.363).IPTW analysis confirmed these negative findings.Conclusion:This study found no evidence of improved outcomes with metformin use in patients with HCC in particular with T2DM receiving A+B therapy.Routine metformin use should not be expected to enhance A+B efficacy based on current evidence.
