Predictive factors for the development of proteinuria in cancer patients treated with bevacizumab, ramucirumab, and aflibercept: a single-institution retrospective analysis

Abstract

The development of proteinuria restricts the dose of anti-angiogenic agents, thereby reducing their efficacy. Thus, this retrospective study was undertaken to identify predictive factors of the development of angiogenesis inhibitor-induced proteinuria, and to elucidate if there is a difference in the likelihood of proteinuria among anti-angiogenic agents or cancer types, to help guide future strategies to improve the safety, efficacy, and quality of life of patients receiving chemotherapy. Between April 2014 and February 2019, 124 cancer patients at our outpatient chemotherapy center who were receiving chemotherapy with bevacizumab, ramucirumab, or aflibercept were enrolled. Variables related to the development of proteinuria were extracted from the patients' clinical records and used for regression analysis. The level of the proteinuria was evaluated based on CTCAE version 5. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the development of proteinuria. The Wilcoxon/Kruskal-Wallis test was used to identify significant differences between groups. Significant factors identified included systolic blood pressure (SBP) [odds ratio (OR) = 1.031, 95% confidence interval (CI) = 1.005-1.058; P = 0.0197], number of cycles (OR = 1.049, 95% CI = 1.018-1.082; P = 0.0019), and calcium channel blocker use (OR = 2.589, 95% CI = 1.090-6.146; P = 0.0311). There was no difference among the three anti-angiogenic agents (P = 0.4969) or among cancer types (P = 0.2726) in the likelihood of proteinuria. In conclusion, SBP, number of cycles, and calcium channel blocker use were identified as significant predictors of the development of angiogenesis inhibitorinduced proteinuria. There was no difference among the three anti-angiogenic agents or among cancer types. Anti-angiogenic agents targeting the human vascular endothelial growth factor pathway, such as bevacizumab, ramucirumab, and aflibercept, significantly improve overall survival and progression-free survival in colorectal, lung, gastric, breast cancers and so on 1-5. The toxicity profile of anti-angiogenic agents differs from those of conventional cytotoxic anticancer agents; use of anti-angiogenic agents is commonly associated with elevated

Nintedanib-Induced Renal Thrombotic Microangiopathy

“…The predictive factors for the development of proteinuria in patients receiving anti-VEGF therapy were identified as high systemic blood pressure, calcium channel blocker administration, and a higher number of therapy cycles [ 14 ]. Our patient had used a calcium channel blocker, but his systolic blood pressure remained high.…”

Nephrotoxicity Associated with Novel Anticancer Agents (Aflibercept, Dasatinib, Nivolumab): Case Series and Nephrological Considerations

“…The increased loss of proteins in urine (proteinuria) represents a common event in cancer patients treated with angiogenesis inhibitors, though its incidence may be vary from study to study. Significant predictors for the development of proteinuria may include the number of cycles (>13), the systolic blood pressure at baseline ≥ 135 mmHg, and the use of calcium channel blockers [ 20 ]. Systemic hypertension is a postulated pathogenic mechanism in the development of such proteinuria, through an increase in intraglomerular pressure [ 11 ].…”

Elucidation of optimal proteinuria management based on the risk of ramucirumab‑induced proteinuria

“…However, in the present study, the combination of paclitaxel with ramucirumab in patients with gastric cancer was not identified as a risk factor for proteinuria. It has been reported that the total dose of bevacizumab is a risk factor for proteinuria (6,13). The target drugs evaluated by Kanbayashi et al (13) were bevacizumab, ramucirumab and aflibercept, which may be a factor contributing to this observation.…”

“…It has been reported that the total dose of bevacizumab is a risk factor for proteinuria (6,13). The target drugs evaluated by Kanbayashi et al (13) were bevacizumab, ramucirumab and aflibercept, which may be a factor contributing to this observation. However, despite drug differences, the total dose was not a risk factor in the present study.…”