Early Tumor Response and Safety of Atezolizumab Plus Bevacizumab for Patients with Unresectable Hepatocellular Carcinoma in Real-World Practice

SIMPLE SUMMARY: Although atezolizumab plus bevacizumab combination therapy was approved in September 2020 as the first immune-combined therapy for hepatocellular carcinoma, the efficacy and safety of this therapy are unclear in real-world practice. This study investigated the early antitumor effects of atezolizumab plus bevacizumab using imaging and tumor markers, and early safety using the frequency of adverse events and the change in hepatic reserve function, especially for patients with a history of previous systemic treatment. The decreased level of serum α-fetoprotein may reflect the early tumor response in atezolizumab plus bevacizumab, and this therapy is safe in all patients, including those in which it was used as a second-line or later treatment. ABSTRACT: The aim of this study was to investigate the early tumor response and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma in real-world practice. Forty patients with Child-Pugh class A liver function and eastern cooperative oncology group performance status 0 or 1 were enrolled. The objective response rate (ORR) at six weeks after the start of treatment, changes in α-fetoprotein (AFP) and des-γ-carboxyprothrombin, incidence of adverse events (AEs), and changes in albumin-bilirubin (ALBI) score and serum ammonia level, were evaluated. Among 40 patients, 24 had histories of prior molecular targeted agents (MTAs). The ORR was 22.5% based on mRECIST. Multivariate analysis showed that an AFP ratio <1.0 at three weeks (odds ratio 39.2, 95% confidence interval CI 2.37–649.0, p = 0.0103) was the only significant factor for predicting early response. There was no significant difference in the frequency of AEs between patients receiving first-line treatments and others. Fatigue, proteinuria, and ascites were more frequent in patients who experienced prior treatment. No decrease in ALBI score or increase in serum ammonia level was observed. Our study demonstrated that AFP may be useful in assessing early response and that this treatment is safe, including in patients with prior MTA treatments.