Risk Factors for Early Onset of Proteinuria in Patients Receiving Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma

INTRODUCTION: Proteinuria is one of the adverse events of atezolizumab plus bevacizumab combination therapy (Atezo + Bev) and can cause interruption in the use of Bev. However, the risk factors for proteinuria in patients with hepatocellular carcinoma (HCC) who are receiving Atezo + Bev have not yet been investigated. The aim of this study was to identify the risk factors for early onset of proteinuria in Atezo + Bev for patients with unresectable HCC. METHODS: Sixty-four patients with Child-Pugh scores of 5–7, an Eastern Cooperative Oncology Group performance status of 0 or 1, and low level of proteinuria (1+ or less on a dipstick test and urine protein-to-creatinine ratio (UPCR) less than 2.0 g/g Cr) at the initiation of therapy were analyzed. The level of proteinuria was evaluated based on the Common Terminology Criteria for Adverse Events version 5.0. We adopted the UPCR for the quantitative test instead of a 24-h urine collection. The incidence of proteinuria and changes in liver function were retrospectively investigated. RESULTS: The cumulative incidence of proteinuria over a 24-week period was 34.4%. Multivariate analysis showed that a low estimated glomerular filtration rate (hazard ratio [HR], 3.807; 95% confidence interval [CI], 1.579–9.180; p = 0.003), treatment for hypertension (HR, 6.224; 95% CI, 1.614–24.010; p = 0.008), and high systolic blood pressure (SBP) (HR, 2.649; 95% CI, 1.133–6.194; p = 0.025) were risk factors for proteinuria. Serum albumin levels and albumin-bilirubin scores in patients with proteinuria worsened. In addition, a mean SBP ≥135 mm Hg during treatment was the only risk factor for the development of severe proteinuria (UPCR >2 g/g Cr). CONCLUSION: Our study found that controlling blood pressure is extremely important for the management of proteinuria in patients with HCC who are receiving Atezo + Bev.