DOI: 10.25934/pr00008236
title: The role of prior transarterial chemoembolization in atezolizumab plus bevacizumab in hepatocellular carcinoma

description: Primary liver cancer is the sixth most diagnosed cancer and the third leading cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Most HCC patients are diagnosed at unresectable stages (cannot be removed through surgery) and the prognosis remains dismal. Further study is needed for the effective treatments of HCC. Chemotherapy uses anti-cancer (cytotoxic) drugs to destroy cancer cells. Chemoembolization is a treatment that entails intra-arterial infusion (inject inside the artery) of a cytotoxic agent directly into the liver used in HCC. When chemotherapy is administered into the blood vessel that feeds the tumor, small particles are injected into the blood vessel to block off (embolize) the blood supply. This is called transarterial chemoembolization (TACE). TACE is recommended as the standard treatment of intermediate HCC worldwide and is widely used in advanced HCC besides the intermediate stage in real-world practice. 
Recently, IMbrave 150 trial successfully explored the efficacy of atezolizumab plus bevacizumab with a good safety profile. Atezolizumab which is an anti-programmed death-ligand 1 agent, is also known as an immune checkpoint inhibitor. Programmed-death ligand 1 (PD-L1) is a protein found in cells that keep a person’s immune system responses under control. Cancer cells may have more of these proteins than normal and an anti-programmed death-ligand 1 drug blocks PD-L1 and allow the immune system to attack cancer. Bevacizumab is an anti-vascular endothelial growth factor (anti-VEGF) agent which reduces the growth of primary tumors by blocking blood vessel growth. TACE results in the death of the tumor cells and releases tumor antigens which may cause the body's immune system to attach the tumor cells. Several animal studies have confirmed this synergistic anti-tumor effect. Based on this theoretical basis, TACE has the potential to help atezolizumab and bevacizumab work better and enhance treatment efficacy. The effectiveness of this combination has not yet been verified in the clinical setting.
In IMbrave 150 trial, 336 patients with HCC received atezolizumab plus bevacizumab with 161 (47.9%) patients receiving the prior local therapy (mainly targets tumors in the liver, including TACE treatment [N=130, 38.7%]). Subgroup analysis shows survival benefit was generally consistent across patients who underwent prior local therapy. However, the survival benefits and safety profile in the atezolizumab plus bevacizumab group with prior TACE versus those TACE-naïve (no prior TACE treatment) was unknown. How to perform TACE and when to perform TACE, if feasible, could be explored and are also crucial to clinical practice. More analyses are required to further explore.
The purpose of this study is to evaluate the safety and efficacy of prior TACE treatment versus TACE-naïve (no prior TACE treatment) in HCC patients who were treated with atezolizumab plus bevacizumab, based on individual patient data from the IMbrave 150 trial. This study could provide proper evidence for this key clinical question and would be essential to guide future clinical trials and clinical practice.