Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway

Abstract

Background VEGF signaling pathway inhibitor (anti-VEGF) therapy is associated with hypertension, but little is known about predisposing clinical characteristics. This study describes the real-world association between baseline clinical characteristics, blood pressure (BP) response, and survival in patients prescribed anti-VEGF therapies. Methods Clinical data from Partners HealthCare in Massachusetts was obtained from adults treated with anti-VEGF therapies (2002–2013). Treatment-induced hypertensive response was defined as worsening of pre-existing hypertension or new diagnosis of hypertension (if no prior hypertension history). Results Data from 1120 patients with renal cell carcinoma (32.2%), hepatocellular carcinoma (11.6%), gastrointestinal stromal tumors (12.5%) and other sarcomas (15.3%) were analyzed. Most patients received sunitinib (52%), sorafenib (25.9%) or pazopanib (18%). A treatment-induced hypertensive response was identified in 49.7% of treated patients. Pre-existing hypertension, present in 65.4%, was an independent risk factor for BP elevation (odds ratio (OR) 1.56, 95% confidence interval (CI) 1.27–1.92); other risk factors included age ≥60 years (OR 1.26, 95%CI 1.06–1.52), and body mass index (BMI) ≥25 kg/m2 (OR 1.26, 95%CI 1.04–1.53). Race, gender, anti-VEGF therapy prescribed, and baseline antihypertensive class were not significant risk factors. The absolute observed mean increase in BP was 21 mmHg (systolic) / 15 mmHg (diastolic), both in patients with and without pre-existing hypertension. The development of hypertension predicted improved survival (hazard ratio 0.76, 95%CI 0.65–0.89). Conclusions Pre-existing hypertension, age, and BMI identify patients at risk for significant anti-VEGF therapy-induced BP elevation. Hypertension appears to be a clinical biomarker of efficacy to anti-VEGF therapies in a broad range of malignancies.

A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma

“…In addition to its control of multiple tumorigenic gene products, specific inhibition of tumor-derived VEGF-A inhibition distinguishes HIF2a antagonists from the currently approved antiangiogenic therapies whose systemic angiogenesis inhibition leads to cardiovascular safety concerns. In particular, hypertension is one of the most frequently observed adverse effects in patients treated with anti-VEGF therapy and can often be dose limiting (34,38). Under conditions in which sunitinib causes a large increase in blood pressure in rats, no change is observed with PT2385 treatment (Fig.…”

“…Hypertension is a common side effect of antibodies and tyrosine kinase inhibitors that target VEGF/VEGFR2 signaling cancerres.aacrjournals.org Downloaded from (33)(34)(35). As PT2385 inhibits VEGF-A production in tumor cells, it is of interest to examine whether it elicits hemodynamic effects in a rodent model (36).…”

Mechanisms of Hypertension and Renal Injury During Vascular Endothelial Growth Factor Signaling Inhibition

“…In addition, age >60 years and body mass index >25 kg/m 2 , but not the different RTKIs applied, emerged as independent risk factors. 22 Because the development of hypertension in response to VSP inhibition can occur within hours to days, close monitoring of BP after initiation of a VSP inhibitor is mandatory. 23 The development of VSP inhibition-induced hypertension has been reported to associate with prolonged progression-free and total survival in patients with various forms of cancer.…”

Hipertensión arterial y tratamiento del cáncer

“…En este registro el incremento absoluto promedio de la PA fue 21 mmHg (sistólica)/15 mmHg (diastólica), tanto en pacientes con HTA preexistente o sin ella (24) . Dos trabajos que realizaron registros de monitoreo ambulatorio de PA durante los primeros días de tratamiento con sorafenib o sunitinib mostraron incremento promedio de PA de similar o mayor magnitud que las referidas (25,26) .…”