Risk of hand-foot skin reaction associated with vascular endothelial growth factor-tyrosine kinase inhibitors: A meta-analysis of 57 randomized controlled trials involving 24,956 patients

Fengxia Ding; Bo Liu; Yaping Wang

doi:10.1016/j.jaad.2019.04.021

Risk of hand-foot skin reaction associated with vascular endothelial growth factor-tyrosine kinase inhibitors: A meta-analysis of 57 randomized controlled trials involving 24,956 patients

J Am Acad Dermatol. 2020 Sep;83(3):788-796. doi: 10.1016/j.jaad.2019.04.021. Epub 2019 Apr 13.

Authors

Fengxia Ding¹, Bo Liu², Yaping Wang³

Affiliations

¹ 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, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China. Electronic address: 482613@hospital.cqmu.edu.cn.
² Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China; Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China.
³ 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, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, China.

PMID: 30991119
DOI: 10.1016/j.jaad.2019.04.021

Abstract

Background: Multiple randomized controlled trials have assessed hand-foot skin reaction (HFSR) caused by vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs).

Objective: We performed a meta-analysis to determine the incidence and the relative risk (RR) of HFSR associated with these agents.

Methods: Databases were searched for relevant studies. Statistical analyses were conducted to calculate the summary incidences, RR, and 95% confidence intervals (CIs) by using random-effects or fixed-effects models according to the heterogeneity of the included studies.

Results: A total of 24,956 patients from 57 studies were included. The overall incidence of all-grade and high-grade HFSR associated with VEGFR-TKIs was 35.0% (95% CI, 28.6%-41.6%) and 9.7% (95% CI, 7.3%-12.3%), respectively. The use of VEGFR-TKIs significantly increased the risk of developing all-grade (RR, 5.09; 95% CI, 3.52-7.35; P < .001) and high-grade (RR, 9.42; 95% CI, 5.59-15.90; P < .001) HFSR. Subgroup analyses revealed that the risk of HFSR was significantly increased according to tumor type, VEGFR-TKI, trial phase, treatment regimen, and control therapy. No evidence of publication bias was observed.

Limitation: High heterogeneity in most studies.

Conclusion: High risk of HFSR is prone to develop in cancer patients receiving VEGFR-TKIs.

Keywords: VEGFR-TKIs; cancer; hand-foot skin reaction; meta-analysis.

MeSH terms

Angiogenesis Inhibitors / administration & dosage
Angiogenesis Inhibitors / adverse effects*
Dose-Response Relationship, Drug
Drug Administration Schedule
Hand-Foot Syndrome / diagnosis
Hand-Foot Syndrome / epidemiology*
Hand-Foot Syndrome / etiology
Hand-Foot Syndrome / prevention & control
Humans
Incidence
Neoplasms / drug therapy*
Network Meta-Analysis
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / adverse effects*
Randomized Controlled Trials as Topic
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
Risk Assessment / statistics & numerical data
Severity of Illness Index
Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

Angiogenesis Inhibitors
Protein Kinase Inhibitors
VEGFA protein, human
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor