Hypertension as an Adverse Event Potentially Impacting the Therapeutic Efficacy of Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma

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BACKGROUND AND AIM: Atezolizumab plus bevacizumab is used as a first-line treatment for unresectable hepatocellular carcinoma (uHCC). However, the relationship between its adverse events (AEs) and treatment efficacy remains unclear. In this study, we aimed to clarify this association. METHODS: This study included 187 patients with uHCC treated with atezolizumab plus bevacizumab as first-line therapy at 19 affiliated hospitals in the Osaka Liver Forum. A landmark analysis was conducted to address biases in AE incidence. RESULTS: The objective response and disease control rates were 28.2% and 69.6%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 7.4 and 24.6 months, respectively. Among the 187 patients, 178 (95.2%) experienced at least one AE, with proteinuria being the most common (41.7%), followed by hypertension (34.8%) and fatigue (30.5%). All three major AEs had a median onset time of 6 weeks. We set the landmark point at Week 9 after treatment initiation, considering that the onset time for most AEs was within 9 weeks. In the landmark analysis, multivariable analysis identified the absence of bevacizumab interruption within 9 weeks and the occurrence of hypertension within 9 weeks as predictors of prolonged PFS. mALBI Grade 1/2a, the occurrence of hypertension, and the absence of fatigue and rash within 9 weeks were associated with prolonged OS. These results were consistent with those from the 6-week landmark analysis. CONCLUSIONS: Patients with hypertension occurring as an AE within 9 weeks are expected to have better PFS and OS with atezolizumab plus bevacizumab therapy for uHCC.

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