Impact of body mass index in patients receiving atezolizumab plus bevacizumab for hepatocellular carcinoma

Hepatol Int. 2023 Aug;17(4):904-914. doi: 10.1007/s12072-023-10491-3. Epub 2023 Apr 1.

Abstract

Background: Atezolizumab plus bevacizumab (Atezo/Bev) is first line-treatment for unresectable hepatocellular carcinoma (HCC). Body mass index (BMI) has demonstrated predictive value for response to immunotherapy in non-HCC cancer types. Our study investigated the effect of BMI on safety and efficacy of real-life use of Atezo/Bev for unresectable HCC.

Methods: 191 consecutive patients from seven centres receiving Atezo/Bev were included in the retrospective study. Overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and disease control rate (DCR) defined by RECIST v1.1 were measured in overweight (BMI ≥ 25) and non-overweight (BMI < 25) patients. Treatment-related adverse events (trAEs) were evaluated.

Results: Patients in the overweight cohort (n = 94) had higher rates of non-alcoholic fatty liver disease (NAFLD) and lower rates of Hepatitis B compared to non-overweight cohort (n = 97). Baseline Child-Pugh class and Barcelona Clinic Liver Cancer stage were similar between cohorts, with lower rates of extrahepatic spread in the overweight group. Overweight patients had similar OS compared to non-overweight (median OS 15.1 vs. 14.9 months; p = 0.99). BMI did not influence median PFS (7.1 vs. 6.1 months; p = 0.42), ORR (27.2% vs. 22.0%; p = 0.44) and DCR (74.1% vs. 71.9%; p = 0.46). There were higher rates of atezolizumab-related fatigue (22.3% vs. 10.3%; p = 0.02) and bevacizumab-related thrombosis (8.5% vs. 2.1%; p = 0.045) in the overweight patients, but overall trAEs and treatment discontinuation were comparable between cohorts.

Conclusion: Atezo/Bev has comparable efficacy in overweight HCC patients, with an increase in treatment-related fatigue and thrombosis. Combination therapy is safe and efficacious to use in overweight patients, including those with underlying NAFLD.

Keywords: Anti-programmed death-ligand; Anti-vascular endothelial growth factor; Checkpoint inhibitor; Cirrhosis; Immunotherapy; Non-alcoholic fatty liver disease; Obesity; Overall survival; Overweight; Progression-free survival.

MeSH terms

  • Bevacizumab / therapeutic use
  • Body Mass Index
  • Carcinoma, Hepatocellular* / drug therapy
  • Fatigue
  • Humans
  • Liver Neoplasms* / drug therapy
  • Non-alcoholic Fatty Liver Disease*
  • Retrospective Studies
  • Ubiquitin-Protein Ligases

Substances

  • atezolizumab
  • Bevacizumab
  • Ubiquitin-Protein Ligases