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.
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.
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.|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.
Bo
B
Liu
Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China.|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.
Fengxia
F
Ding
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.|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.
Yang
Y
Liu
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Geng
G
Xiong
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Tao
T
Lin
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Dawei
D
He
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Yuanyuan
Y
Zhang
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.|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.
Deying
D
Zhang
Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Guanghui
G
Wei
D000970:Antineoplastic Agents / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000453:epidemiology; D015994:Incidence; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor
VEGFR-TKIs; cancer; hypertensive events; meta-analysis