Incidence and risk of hypertension associated with vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: a comprehensive network meta-analysis of 72 randomized controlled trials involving 30013 patients

Bo Liu, Fengxia Ding, Yang Liu, Geng Xiong, Tao Lin, Dawei He, Yuanyuan Zhang, Deying Zhang _ and Guanghui Wei

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Oncotarget. 2016; 7:67661-67673. https://doi.org/10.18632/oncotarget.11813

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Bo Liu1,3, Fengxia Ding2,3, Yang Liu1,3, Geng Xiong1,4, Tao Lin1, Dawei He1, Yuanyuan Zhang4, Deying Zhang1,3 and Guanghui Wei1

1 Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, China

2 Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, China

3 Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing, China

4 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA

Correspondence to:

Deying Zhang, email:

Guanghui Wei, email:

Keywords: meta-analysis, cancer, VEGFR-TKIs, hypertensive events

Received: April 28, 2016 Accepted: August 23, 2016 Published: September 01, 2016


Background: Tyrosine kinase inhibitors (TKIs) have been developed during the last decade that target the vascular endothelial growth factor receptor (VEGFR) are currently being evaluated as treatments for malignant tumors. The increased application of VEGFR-TKIs means that the probability of hypertension is a serious concern. However, the reported incidence varies markedly between clinical trials. Here, we undertook an up-to-date, comprehensive meta-analysis on clinical works to build the incidence of hypertension along with VEGFR-TKIs. The goal was to understand better of the overall venture of cancer patients’ hypertension treated with these drugs.

Methods: Databases (EMBASE, PubMed, and Cochrane library) and the abstracts of the American Society of Clinical Oncology annual meeting and European Society of Medical Oncology were searched to identify related studies. 95% confidence intervals (CIs), summary incidences, and relative risk (RR) were calculated utilizing either fixed-effects models on the basis of the heterogeneity of the included studies or random-effects.

Results: Seventy-two randomized controlled trials (including 30013 patients) were involved. The total incidence of high-grade and all-grade hypertensive events along with VEGFR-TKIs was 23.0% (95% CI, 20.1–26.0%) and 4.4% (95% CI, 3.7–5.0%), respectively. The use of VEGFR-TKIs remarkably enhanced the venture of developing high-grade (RR, 4.60; 95% CI, 3.92–5.40; P < 0.001) and all-grade (RR, 3.85; 95% CI, 3.37–4.40; P < 0.001) hypertensive events. Subgroup analyses revealed that the risk of a hypertensive event varied significantly in accordance with tumor type, VEGFR-TKI, trial phase, VEGFR-TKIs-based regimen, control therapy, and chemotherapy regimen.

Conclusions: Patients with cancer that receive VEGFR-TKIs are at a remarkable venture of developing hypertension. Therefore, suitable treatment and monitoring should be introduced to avoid cardiovascular complications.

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