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 - 20/03/20

Doi : 10.1016/j.jaad.2019.04.021

Fengxia Ding, MD ^a,^b,^⁎ , Bo Liu, MD ^b,^c, Yaping Wang, MD ^a,^b
^a Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China
^b 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
^c Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, China

^∗Correspondence to: Fengxia Ding, MD, Department of Pediatric Respiratory Medicine, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2 RD, Yuzhong District, Chongqing 400014, China.Department of Pediatric Respiratory MedicineChildren's Hospital of Chongqing Medical UniversityNo. 136, Zhongshan 2 RD, Yuzhong DistrictChongqing400014China

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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.

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Key words : cancer, hand-foot skin reaction, meta-analysis, VEGFR-TKIs

Abbreviations used : CI, HFSR, RCT, RR, VEGFR-TKIs

Plan

Materials and methods

Systematic literature search

Incidence of all-grade HFSR

Incidence of high-grade HFSR

RR of HFSR

Risk of HFSR according to tumor type, VEGFR-TKI, trial phase, treatment regimen, and control therapy

Publication bias

Discussion

Conclusions

	Funding source: Program (81800618) of the Natural Science Foundation of China.
	Conflicts of interest: None disclosed.
	Reprints not available from the authors.