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

Yuwa Ando; Tomokazu Kawaoka; Masanari Kosaka; Yuki Shirane; Yusuke Johira; Ryoichi Miura; Serami Murakami; Shigeki Yano; Kei Amioka; Kensuke Naruto; Yumi Kosaka; Shinsuke Uchikawa; Kenichiro Kodama; Hatsue Fujino; Takashi Nakahara; Atushi Ono; Eisuke Murakami; Masami Yamauchi; Wataru Okamoto; Shoichi Takahashi; Michio Imamura; Hiroshi Aikata

doi:10.1159/000528145

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

Liver Cancer. 2022 Nov 29;12(3):251-261. doi: 10.1159/000528145. eCollection 2023 Aug.

Authors

Yuwa Ando¹, Tomokazu Kawaoka¹, Masanari Kosaka¹, Yuki Shirane¹, Yusuke Johira¹, Ryoichi Miura¹, Serami Murakami¹, Shigeki Yano¹, Kei Amioka¹, Kensuke Naruto¹, Yumi Kosaka¹, Shinsuke Uchikawa¹, Kenichiro Kodama¹, Hatsue Fujino¹, Takashi Nakahara¹, Atushi Ono¹, Eisuke Murakami¹, Masami Yamauchi^{1

2}, Wataru Okamoto^{1

2}, Shoichi Takahashi¹, Michio Imamura¹, Hiroshi Aikata¹

Affiliations

¹ Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
² Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan.

Abstract

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.

Keywords: Adverse events; Atezolizumab plus bevacizumab; Hepatocellular carcinoma; Proteinuria; Vascular endothelial growth factor.

Grants and funding

The authors did not receive any funding for this study.