171P - Retrospective study of the correlation between proteinuria and renal function in patients (pts) with unresectable hepatocellular carcinoma (uHCC) treated with atezolizumab plus bevacizumab (Atezo+Bev): ARISE study

Background

Atezo+Bev is recognized as the standard of care for systemic treatment-naïve uHCC pts. The key to prolonging survival is to manage vascular endothelial growth factor inhibitor-related adverse events while considering continued treatment. Proteinuria is the main adverse event leading to Bev interruption. However, the relationship between Bev-related proteinuria and renal dysfunction is unclear. Therefore, we retrospectively investigated the impact of proteinuria after starting Atezo+Bev on renal function in uHCC pts.

Methods

We performed a single-arm retrospective study of 100 uHCC pts treated with Atezo+Bev between Sep 25, 2020 and May 31, 2022, at Kindai University, 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 100 pts with data at baseline and at least twice after starting Atezo+Bev. The median age was 74 years (range 41‒89) and 75% were male. Performance status was 0–1 in 99% and 2 in 1%. Barcelona Clinic Liver Cancer stage was B in 62% and C in 38%. Child–Pugh class was A5, A6, in 61%, 29%. 60% had hypertension and 37% had diabetes mellitus. During the Atezo+Bev treatment period, 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 interval) between the maximum UPCR increase and the maximum eGFR decline were −0.13 (−0.32 to 0.07) and −0.13 (−0.32 to 0.07), respectively.

Conclusions

The change in UPCR was not correlated with the change in eGFR during Atezo+Bev treatment. For safety concerns, Bev interruption criteria are set according to the degree of proteinuria, but we found that proteinuria does not necessarily impair renal function. Physicians should consider the risk-benefit profile when deciding whether to skip Bev in pts who develop proteinuria during treatment.

Clinical trial identification

UMIN000050692.

Editorial acknowledgement

Medical writing support was provided by Nicholas D. Smith (EMC K.K.), and funded by Chugai Pharmaceutical Co., Ltd.

Legal entity responsible for the study

Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine.

Funding

Chugai Pharmaceutical Co., Ltd.

Disclosure

K. Ueshima: Financial Interests, Personal, Invited Speaker, Concurrent roles with an advisory board: Chugai, Eisai, Takeda, Lilly Japan; Financial Interests, Personal, Invited Speaker: AstraZeneca, Otsuka, Taiho, Sumitomo, MSD, Kowa, EA pharma, AbbVie, Aska; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Local PI: Chugai. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Liiy, Bayer, Takeda, AstraZeneca; Financial Interests, Institutional, Research Grant: Otsuka, EA Pharma, Taiho, Eisai, AbbVie, GE Healthcare, Chugai. All other authors have declared no conflicts of interest.