Risk Factors Identified for Hypertension, Proteinuria Due to VSPIs for Cancer – Renal and Urology News

Vascular endothelial growth factor signaling pathway inhibitors (VSPIs) for cancer are often discontinued due to high-grade hypertension and proteinuria, a new study finds. Investigators have identified key risk factors.

Shruti Gupta, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues examined risk factors and time to onset of VSPI-associated grade 3 or higher hypertension and grade 2 or higher proteinuria among 5236 adults with cancer treated from 2016 to 2023 at Massachusetts General Hospital and Dana-Farber Cancer Institute in Boston. VSPIs included anti-vascular endothelial growth factor (VEGF) angiogenic agents, tyrosine kinase inhibitors (TKIs), and multikinase inhibitors.

The 590 patients who developed grade 3 or higher hypertension were more likely to have hypertension, lower estimated glomerular filtration rate (eGFR), and a history of genitourinary cancer at baseline. Nephrectomy for kidney cancer is known to increase risk for de novo arterial hypertension and proteinuria, according to Dr Gupta’s team, so these patients “warrant closer monitoring for VSPI-associated hypertension and proteinuria.” The 507 patients with grade 2 or higher proteinuria were more likely to have baseline diabetes, coronary artery disease, congestive heart failure, and lower eGFR. Severe hypertension and proteinuria occurred across different drug classes. Grade 3 or higher hypertension, however, was most frequently among axitinib (42%) and aflibercept (45%) users. Grade 2 or higher proteinuria was most common among aflibercept (64%) and sorafenib (61%) users. Onset of severe hypertension or proteinuria occurred at a median 112 and 110 days, respectively. Proteinuria onset was quickest among TKI users (61 days), and hypertension onset was quickest among multikinase inhibitor users (87 days).

Strong risk factors for high-grade higher hypertension included age older than 70 years, genitourinary cancer, and direct anti-VEGF angiogenic agents, according to multivariable-adjusted analyses, the investigators reported. Other predictors included female sex, baseline hypertension, eGFR less than 90 mL/min/m², and serum magnesium less than 1.8 mg/dL. The strongest risk factors for high-grade proteinuria were coronary artery disease, baseline systolic blood pressure exceeding 160 mm Hg, hemoglobin less than 11 g/dL, and use of multikinase inhibitors. Higher doses of pazopanib and sunitinib were associated with both high-grade hypertension and proteinuria.

Within 60 days of the onset of high-grade hypertension or proteinuria 35% and 44% discontinued VSPIs, respectively. Cessation of these potentially life-saving cancer treatments should be avoided if possible, according to Dr Gupta’s team. They noted that management of VSPI-associated hypertension and proteinuria may include dose-reduction, or the addition of other antihypertensives or antiproteinuric agents.

“Modifiable risk factors (e.g., hypomagnesemia, anemia) should be aggressively managed, and patients who are at highest risk should undergo more frequent blood pressure and proteinuria monitoring in order to prevent progression to high-grade hypertension and proteinuria,” Dr Gupta’s team wrote.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.