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

Cancer. 2015 Jan 15;121(2):311-9. doi: 10.1002/cncr.28972. Epub 2014 Sep 18.


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 preexisting 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. Preexisting 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/m(2) (OR, 1.26; 95% CI, 1.04-1.53). Race, sex, anti-VEGF therapy prescribed, and baseline antihypertensive class were not significant risk factors. The absolute observed mean increase in BP was 21 mm Hg (systolic)/15 mm Hg (diastolic), both in patients with and without preexisting hypertension. The development of hypertension predicted improved survival (hazard ratio, 0.76; 95% CI, 0.65-0.89).

Conclusions: Preexisting 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 of anti-VEGF therapies in a broad range of malignancies.

Keywords: angiogenesis inhibitors; antihypertensive agents; hypertension; pazopanib; risk factors; sorafenib; sunitinib; survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Blood Pressure / drug effects
  • Body Mass Index
  • Disease Progression
  • Female
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / diagnosis
  • Hypertension / drug therapy
  • Hypertension / metabolism*
  • Male
  • Middle Aged
  • Neoplasms / drug therapy
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Antihypertensive Agents
  • Antineoplastic Agents
  • Vascular Endothelial Growth Factor A