Higher Risk of Proteinuria with Atezolizumab plus Bevacizumab than Lenvatinib in First-Line Systemic Treatment for Hepatocellular Carcinoma.

Introduction: Proteinuria presents a challenging complication during systemic therapy for hepatocellular carcinoma (HCC). This study aims to identify risk factors for proteinuria in patients with HCC treated with atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic treatment.

Methods: A retrospective analysis was conducted on 622 consecutive patients with unresectable HCC who received Atezo/Bev or LEN as first-line systemic treatment between October 2013 and October 2022. Cumulative incidence of proteinuria was estimated using Kaplan-Meier curves and compared using log-rank tests. Risk factors for proteinuria were identified using Cox proportional-hazard models, along with propensity score-matched and subgroup analyses.

Results: Among 367 patients treated with Atezo/Bev and 255 with LEN, the cumulative incidence of proteinuria at 12 months was 27.5%. In the multivariable analysis, Atezo/Bev treatment (adjusted HR [aHR]: 1.57; 95% CI: 1.03-2.42), diabetes (aHR: 1.64; 95% CI: 1.03-2.61), hypertension (aHR: 2.27; 95% CI: 1.04-4.97), Child-Pugh class B (aHR: 3.43; 95% CI: 1.34-8.78), macrovascular invasion (MVI; aHR: 1.58; 95% CI: 1.04-2.38), and an estimated glomerular filtration rate ≤60 mL/min/1.73 m² (aHR: 3.21; 95% CI: 1.84-5.62) were identified as risk factors for proteinuria. A higher risk of proteinuria in Atezo/Bev patients compared with LEN was consistently observed in the PS-matched cohort, particularly pronounced in subgroups with MVI (HR: 2.84; 95% CI: 1.23-6.54) compared with those without MVI (HR: 1.31; 95% CI: 0.69-2.47).

Conclusions: Patients treated with Atezo/Bev as first-line systemic treatment for HCC exhibited a higher risk of proteinuria compared with those with LEN, particularly when accompanied by MVI.