No Correlation Between Proteinuria and Renal Function in Patients with Unresectable Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: ARISE Study

Background: Atezolizumab plus bevacizumab (Atezo + Bev) is the standard of care for treatment-naïve patients with unresectable hepatocellular carcinoma (uHCC). Proteinuria is a treatment-emergent adverse event that often leads to Bev interruption. However, the relationship between Bev-related proteinuria and renal dysfunction is unclear. We retrospectively investigated the impact of proteinuria after starting Atezo + Bev on renal function in patients with uHCC. Methods: We performed a single-arm retrospective study of patients with uHCC treated with Atezo + Bev between 25 September 2020 and 31 May 2022, at Kindai University Hospital, Japan. The impact of proteinuria on renal function during Atezo + Bev treatment was analyzed in terms of the correlation between changes in urine protein creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) relative to baseline. Results: We analyzed data from 100 patients (median age 74 years; range 41–89; 75% male). During Atezo + Bev treatment, the median (interquartile range) maximum increase from baseline in UPCR was 0.39 (0.08 to 2.05) and the median maximum decline from baseline in eGFR was −7.5 (−20.5 to −3.0) mL/min/1.73 m2. The Pearson and Spearman correlation coefficients (95% confidence intervals) between these variables were −0.16 (−0.34 to 0.04) and −0.13 (−0.32 to 0.07), respectively. Conclusions: We found no correlation between the changes in UPCR and eGFR during Atezo + Bev treatment. Bev interruption criteria are based on the degree of proteinuria; however, our results suggest that proteinuria does not necessarily impair renal function. Physicians should consider the risk–benefit profile when deciding whether to discontinue Bev in patients who develop proteinuria during Atezo + Bev treatment.