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

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.

Keywords: atezolizumab; bevacizumab; hepatocellular carcinoma; immune checkpoint inhibitor; molecular targeted agents; real-world practice; tumor marker; α-fetoprotein.

Figure 1

Changes in AFP and DCP ratios for each response based on mRECIST. In 9 patients with partial response, the AFP ratio at 3 and 6 weeks decreased with a statistically significant difference, and increased with a statistically significant difference in 10 patients with progressive disease. On the other hand, the DCP ratio increased with a statistically significant difference at 6 weeks in patients with stable disease or progressive disease.

Figure 2

Comparison of adverse events between prior MTA therapy and atezolizumab plus bevacizumab. Adverse events found in >50% included hypertension, fatigue, decreased appetite, proteinuria, and thyroid dysfunction with prior MTA therapy, while hypertension, fatigue decreased appetite were seen with atezolizumab plus bevacizumab.

Figure 3

Change in albumin–bilirubin (ALBI) score. (A)All patients. (B) Patients treated as first-line treatment. (C) Patients treated as second-line or later treatment. (D) Patients without portal hypertension (PH). (E) Patients with PH.

Figure 4

Change in serum ammonia level. (A) All patients. (B) Patients treated as first-line treatment. (C) Patients treated as second-line or later treatment. (D) Patients without portal hypertension. (E) Patients with portal hypertension. Circles (“°”) mean outliers.