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

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. 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. 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. 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.