Risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors: a network meta-analysis
10.3760/cma.j.cn114015-20210625-00716
- VernacularTitle:血管内皮生长因子受体酪氨酸激酶抑制剂致肿瘤患者发生严重胃肠道事件风险的网状meta分析
- Author:
Junwei HAN
1
;
Yuanping LI
;
Yao CHENG
;
Xiaocheng WANG
;
Min ZHOU
;
Jianbo SONG
Author Information
1. 山西省人民医院药学部，太原 030012
- Publication Type:Journal Article
- Keywords:
Receptors, vascular endothelial growth factor;
Protein-tyrosine kinases;
Diarrhea;
Anorexia;
Nausea;
Vomiting;
Network meta-analysis
- From:
Adverse Drug Reactions Journal
2022;24(3):130-138
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To systematically evaluate the risk of severe gastrointestinal events in patients with cancer caused by vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI).Methods:Randomized controlled trials of VEGFR-TKI in the treatment of tumors were collected by searching relevant databases at home and abroad (up to March 2, 2019). The patients who were treated with a VEGFR-TKI were enrolled into the trial group, and those who received placebo or another VEGFR-TKI were enrolled into the control group. The outcomes included the incidence of serious gastrointestinal events. The Jadad scoring method was used to assess the quality of included studies. The Review Manager 5.3 software was used for direct meta-analysis on the risk of severe gastrointestinal events. Stata 13.0 software and linear mixed model based on frequency framework were used for network meta-analysis on severe gastrointestinal events at the highest risk. The results were expressed by relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 38 studies were included in the analysis, all of which were high-quality studies (Jadad score 4-7), comprising a total of 15 217 patients (9 130 in the trial group and 6 087 in the control group). The results of direct meta-analysis showed that the risks of severe diarrhea, severe anorexia, and severe nausea in the trial group were higher than those in the control group respectively, and the differences were statistically significant [6.8% (602/8 894) vs. 0.7% (49/6 584), RR=6.62 (95 %CI: 5.00-8.76), P<0.001; 2.5% (201/7 937) vs. 0.7% (41/5 831), RR=2.14 (95 %CI: 1.40-3.25), P<0.001; 1.5% (92/6 343) vs. 0.4% (21/4 870), RR=1.95 (95 %CI: 1.23-3.12), P=0.005]; the risk of severe diarrhea was the highest [6.8% (602/8 894)]. There was no significant difference in the risk of severe vomiting and severe abdominal pain compared with the control group [1.4% (79/5 788) vs. 0.7% (32/4 428), RR=1.49 (95 %CI: 0.90-2.47), P=0.120; 1.7% (82/4 766) vs. 1.1% (40/3 628), RR=1.35 (95 %CI: 0.84-2.16), P=0.210]. The results of network meta-analysis on risk of severe diarrhea events showed that the relative risks of severe diarrhea caused by varieties of VEGFR-TKI were axitinib>anlotinib>cabozantinib≈vandetanib≈sunitinib≈lenvatinib≈sorafenib≈pazopanib>regorafenib>fruquintinib>apatinib in the order. Conclusion:The application of VEGFR-TKIs, especially axitinib, can increase the risk of severe diarrhea in patients with tumors, which deserves clinical attention and vigilance.
