Endothelial Growth Factor Inhibitor Therapy Research Articles

Cardiovascular events following vascular endothelial growth factor inhibitor therapy with sunitinib or pazopanib in patients with renal cell carcinoma - a nationwide registry-based follow-up study

Abstract Background Use of oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) with focus on sunitinib and pazopanib approved for treatment of patients with renal cell carcinoma (RCC) may be associated with cardiovascular events. However, there are limited data on the risk related to treatment with sunitinib or pazopanib. Purpose The aim of this study was to examine the risk of cardiovascular events in patients with RCC treated with sunitinib and pazopanib compared with age- and sex-matched population control subjects without cancer (1:2 ratio). Methods Patients with RCC treated with sunitinib or pazopanib from 2011 through 2018 were identified within the Danish National Patient Registry. Multivariable Cox regression standardized to the age, sex, selected comorbidity and pharmacotherapy distributions of all included subjects were used to derive absolute one-year risks of selected cardiovascular events. Results A total of 3,642 patients were included in the analysis, of whom 1,214 had RCC treated with sunitinib or pazopanib, and 2,428 were population control subjects without cancer. Differences in age, sex, prior acute coronary syndrome (ACS), chronic obstructive pulmonary disease, and peripheral artery disease were insignificant (all P>0.05), whereas patients with RCC more frequently had prior hypertension (51.2% vs. 35.2%), diabetes (17.1% vs. 10.3%), and transient ischemic attack (TIA) or stroke (7% vs. 4.5%), all P<0.05. Absolute risk of ACS was 1.4% for patients with RCC vs. 1.0% for controls (P=0.54), stroke/TIA 1.7% vs. 0.8% (P=0.10), and ventricular arrhythmia 0.3% vs. 0.1% (P=0.70). In contrast, risk of hypertension was significantly elevated with 50.7% vs. 41.8% for patients with RRC vs. controls (P<0.001), and this risk was similarly elevated when excluding patients with prior hypertension (30.7% vs. 5.4%, P<0.001). Similarly, risks of atrial fibrillation or flutter (AF) with 5.6% vs. 2.8% (P<0.001) and heart failure (HF) with 0.7% vs. 0.3% (P<0.001) were significantly elevated in patients with RCC versus controls.Risk of venous thromboembolism (VTE) was 5.6% vs. 0.9% (P<0.001) for patients with RCC versus controls. All-cause mortality risk was 40.1% vs. 2.6% (P<0.001). The corresponding relative risks for one-year outcomes are shown in Figure 1. Conclusions Patients with RCC treated with sunitinib or pazopanib did not have a significantly higher risk of ACS, stroke/TIA or ventricular arrhythmia when compared to age- and sex-matched controls. In contrast, risks of hypertension, AF, HF, and VTE at 1 year compared with population control subjects were significantly elevated. Risk of HF risk was however limited in absolute numbers and the clinical significance of the evaluated risk of this endpoint as well as other endpoints should be interpreted in the context of a significantly high 1-year mortality risk of around 40% in patients with RCC versus only around 2.5% in population controls.Figure 1

Intravitreal Vascular Endothelial Growth Factor Inhibitor Therapy in Denmark and 5-Year Projections

This cohort study examines the use of intravitreal injections of vascular endothelial growth factor inhibitor in Denmark from 2007 through 2022 and forecasts future demand for this therapy.

Emotional and physical experiences of people with neovascular age-related macular degeneration during the injection process in Germany: a qualitative study

ObjectivesIn order to better understand the continued barriers to the provision of vascular endothelial inhibitor therapy, this study aims to investigate patients’ experiences with neovascular age-related macular degeneration (nvAMD) in...

SMOKING STATUS AND TREATMENT OUTCOMES OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

To assess whether smoking status affects 1-year visual outcomes in eyes treated with vascular endothelial growth factor inhibitors for neovascular age-related macular degeneration. Retrospective analysis of data from a prospectively designed, multicenter, observational database. Nine hundred and eighty seven treatment-naive eyes of patients with neovascular age-related macular degeneration were tracked by the Fight Retinal Blindness! outcome registry in Australia, New Zealand, Singapore, and Switzerland who had documented smoking status at baseline and commenced vascular endothelial growth factor inhibitor therapy from January 2006 to December 2016. Generalized additive models were used to display visual acuity results. There was a significant difference in mean improvement in visual acuity at 12 months between nonsmokers, ex-smokers, and current smokers (7.7 vs. 6.1 vs. 3.5 letters of change; P = 0.046) among patients who completed 12 months of treatment when adjusted for age, baseline visual acuity, and choroidal neovascular membrane lesion type and nested for practice. There was no significant difference in the median number of injections over 12 months of treatment by smoking status. Current smokers were a mean of 6.2 years younger than nonsmokers when they started treatment (P < 0.001). This study found inferior 12-month visual outcomes in patients who continued to smoke while receiving vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.

Echocardiographic Assessment for the Detection of Cardiotoxicity Due to Vascular Endothelial Growth Factor Inhibitor Therapy in Metastatic Renal Cell and Colorectal Cancers

Cardio-oncology is a recently established discipline that focuses on the management of patients with cancer who are at risk for developing cardiovascular complications as a result of their underlying oncologic treatment. In metastatic colorectal cancer (mCRC) and metastatic renal cell carcinoma (mRCC), vascular endothelial growth factor inhibitor (VEGF-i) therapy is commonly used to improve overall survival. Although these novel anticancer drugs may lead to the development of cardiotoxicity, whether early detection of cardiac dysfunction using serial echocardiography could potentially prevent the development of heart failure in this patient population requires further study. The aim of this study was to investigate the role of two-dimensional speckle-tracking echocardiography in the detection of cardiotoxicity due to VEGF-i therapy in patients with mCRC or mRCC. Patients with mRCC or mCRC were evaluated using serial echocardiography at baseline and 1, 3, and 6months following VEGF-i treatment. A total of 40 patients (34 men; mean age, 63±9years) receiving VEGF-i therapy were prospectively recruited at two academic centers: 26 (65%) were receiving sunitinib, eight (20%) pazopanib, and six (15%) bevacizumab. The following observations were made: (1) 8% of patients developed clinically asymptomatic cancer therapeutics-related cardiac dysfunction; (2) 30% of patients developed clinically significant decreases in global longitudinal strain, a marker for early subclinical cardiac dysfunction; (3) baseline abnormalities in global longitudinal strain may identify a subset of patients at higher risk for developing cancer therapeutics-related cardiac dysfunction; and (4) new or worsening hypertension was the most common adverse cardiovascular event, afflicting nearly one third of the study population. Cardiac dysfunction defined by serial changes in myocardial strain assessed using two-dimensional speckle-tracking echocardiography occurs in patients undergoing treatment with VEGF-i for mCRC or mRCC, which may provide an opportunity for preventive interventions.

Vascular Endothelial Growth Factor Inhibitor Therapy and Cardiovascular and Renal Damage in Renal Cell Carcinoma.

Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited. To evaluate possible renal and CV damage in patients with RCC treated with sunitinib. Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment. Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), hemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001), IVS (p=0.03) and proteinuria (p<0.001), while we showed no significant differences in glycosuria, phosphaturia, serum uric acid, intact parathormone, and LVMI. We observed the development of renal damage and worsening of CV indices in patients treated with sunitinib. We suggest to consider a careful assessment of renal function and CV risk factors, before initiation and during administration of this drug.

Long-term follow-up of vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration

To discuss the most recent literature regarding the long-term use (≥52 weeks of follow-up) of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (NVAMD). Intravitreal ranibizumab has been demonstrated to provide outstanding vision outcomes relative to the standard therapy in patients with NVAMD. The VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD studies showed that patients managed with intravitreal aflibercept achieved visual acuity and anatomic improvements similar to individuals managed with monthly ranibizumab while receiving an average of five fewer injections during the first 12 months of treatment. In the Comparison of AMD Treatment Trials, intravitreal bevacizumab dosed monthly met noninferiority to ranibizumab monthly, as well as noninferiority to ranibizumab dosed as-needed with respect to change in visual acuity 1 year after the treatment initiation. Furthermore, patients switched to as-needed regimens in their second year of follow-up from monthly dosing during the first year demonstrated an incremental loss of visual acuity during the second year of follow-up irrespective of the drug used. To date, trials evaluating anti-VEGF therapy for NVAMD demonstrate a low incidence of serious ocular or systemic adverse events. However, the potential for deleterious effects of long-term (beyond 2 years) pan-VEGF blockade remains unknown. Patients with NVAMD enjoy heretofore unprecedented vision gains when managed with anti-VEGF therapy, and the limited body of evidence to date regarding long-term anti-VEGF treatment shows these vision gains can be maintained through 2 years. Further investigation is needed to explore the effects of long-term anti-VEGF therapy beyond 2 years.