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

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/m2 (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. Cancer 2015;121:311–9. © 2014 American Cancer Society. Older age, higher body mass index, and preexisting hypertension are risk factors for the development of a treatment‐induced hypertensive response to VEGF signaling pathway inhibitors. The development of hypertension was associated with improved survival.