Bevacizumab significantly increases the risks of hypertension and proteinuria in cancer patients: A systematic review and comprehensive meta-analysis

Abstract

Published data regarding the overall risks and incidence of hypertension and proteinuria associated with bevacizumab were still unclear. To quantify the precise risks and incidence, we performed this comprehensive meta-analysis of 72 published clinical trials including 21902 cases and 20608 controls. The overall incidence, risk ratios (RRs), and 95% confidence intervals (95% CIs) were calculated using a fixed or random-effect model based on the heterogeneity. The incidence of all-grade and high-grade hypertension were 25.3% (95% CI: 21.5%−29.5%) and 8.2% (95% CI: 7%−9.8%) for patients treated with bevacizumab. And the incidence of all-grade and high-grade proteinuria were 18% (95% CI: 11.7%−26.6%) and 2.4% (95% CI: 1.8%−3.2%), respectively. Compared with controls, bevacizumab significantly increased the risks of all-grade (RR: 3.595, 95% CI: 2.952−4.378) and high-grade hypertension (RR: 5.173, 95% CI: 4.188−6.390). Obviously increased risks of all-grade (RR: 3.369, 95% CI: 2.492−4.556) and high-grade proteinuria (RR: 5.494, 95% CI: 3.991−7.564) were also observed. In the subgroup analysis, the risks of hypertension and proteinuria may significantly vary with bevacizumab dosage, cancer types and concomitant drugs. Whereas, no obvious difference were discovered when stratified based on phase of trials, age of patients, treatment line and duration. So, close monitor and effective management were highly recommended for the safe use of bevacizumab.

Prognostic factors of refractory NSCLC patients receiving anlotinib hydrochloride as the third- or further-line treatment

“…Similar to EGFR-TKIs 11 , treatment with anlotinib also resulted in hand–foot syndrome, which was considered to be a predictor of good PFS. Meanwhile, similar to antiangiogenic targeting agents 12 , anlotinib caused hypertension and prolonged QT intervals, with the former considered a good predictor of PFS. From the perspective of adverse events, although they have been proven tolerable and transient, anlotinib simultaneously functioned as an antiangiogenic targeting and EGFR-TKI agent.…”

Hypertensive Cardiotoxicity in Cancer Treatment—Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies—Epidemiology, Incidence, and Pathophysiology

“…Hurwitz et al [ 92 , 93 ] in their landmark trial, reported an association between bevacizumab and the development of arterial hypertension of any grade in 22.4% and grade 3 or 4 in 11%, including hypertensive emergencies manifest as posterior reversible leukoencephaly [ 94 ]. Subsequent meta analyses of bevacizumab in other trials have confirmed similar incidence of all grade hypertension in 25% and grade 3/4 in 8% [ 36 ].…”

Effect of a Single Intravitreal Bevacizumab Injection on Proteinuria in Patients With Diabetes

“…14 Proteinuria is the second-most common complication after hypertension following systemic administration of bevacizumab, presenting as increased risk of all-grade proteinuria, high-grade proteinuria (grade 3 or 4), and nephrotic syndrome. 15,16 Moreover, diabetes is a significant risk factor for the development of proteinuria after systemic administration of bevacizumab. 17 Proteinuria is an independent risk factor for morbidity and death in patients with chronic kidney diseases, including diabetic nephropathy (DN).…”