RCC renal function independent of axitinib-induced proteinuria

By Shreeya Nanda, Senior medwireNews Reporter

Treatment with the vascular endothelial growth factor receptor (VEGFR) inhibitor axitinib does not adversely affect renal function in patients with metastatic renal cell carcinoma (RCC) even in the presence of proteinuria, a Japanese study indicates.

Proteinuria is an established risk factor for renal deterioration, explain Hideaki Miyake, from Kobe University Graduate School of Medicine, and colleagues, and add that this dose-related adverse event is observed frequently in patients treated with agents that inhibit components of VEGF-related signalling pathways.

A total of 65 patients with metastatic RCC who received axitinib treatment for a minimum of 12 weeks were included in this retrospective analysis. The median duration of treatment for patients positive (n=41) and negative (n=24) for proteinuria was 12.3 and 13.3 months, respectively.

Although the estimated glomerular filtration rate (eGFR) decreased “slightly” after axitinib treatment, the eGFR values were not significantly different prior to and after the introduction of axitinib in patients with or without proteinuria, the researchers report.

In the proteinuria-positive patients, changes in the eGFR value from baseline were not associated with either the degree of proteinuria, as assessed by the urine protein to creatinine ratio at the last clinic visit, or with the duration of axitinib therapy.

Additionally, univariate analysis showed that age (≥65 years), the eGFR value prior to the introduction of axitinib (<45 mL/min per 1.73 m²) and the timing of axitinib introduction (as third-line treatment), but not proteinuria, were significant predictors of impaired renal function after axitinib treatment, defined as a greater than 10% decrease in eGFR.

Of these, only age remained significantly associated with decreased eGFR after adjusting for the other factors, leading the team to observe that “it is important to pay special attention to elderly patients with [metastatic] RCC who are undergoing treatment with axitinib by closely observing the changes in renal function, considering the possible development of severe renal injury.”

Miyake et al conclude in the International Journal of Clinical Oncology: “[T]hese findings strongly suggest that axitinib-induced proteinuria may not have an adverse impact on renal function in patients with [metastatic] RCC.”

However, highlighting the short observation period of their study, they say that “whether or not the long-term renal function is affected by the presence of axitinib-induced proteinuria should be assessed.”

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