The safety of combination of ipilimumab and chemotherapy for advanced solid tumors: a meta-analysis
10.3760/cma.j.cn114015-20200509-00515
- VernacularTitle:伊匹木单抗联合化疗治疗晚期实体肿瘤安全性的meta分析
- Author:
Xiaodi GUO
1
;
Wendong LI
1
;
Jinglong CHEN
1
Author Information
1. 首都医科大学附属北京地坛医院肿瘤内科 100015
- Publication Type:Journal Article
- Keywords:
Ipilimumab;
Antineoplastic agents, immunological;
Drug-related side effects and adverse reactions;
Antineoplastic combined chemotherapy protocols;
Meta-an
- From:
Adverse Drug Reactions Journal
2020;22(7):385-392
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To systematically evaluate the safety of immune checkpoint inhibitor ipilimumab combined with chemotherapy for advanced solid tumors.Methods:Randomized controlled trials (RCTs) of ipilimumab combined with chemotherapy (the trial group) versus placebo combined with chemotherapy (the control group) for advanced solid tumors were collected by searching related databases (up to April 30, 2020). The outcome indicators were treatment-related adverse events (AEs), including fatigue, rash, nausea, diarrhea, neutropenia, alanine aminotransferase (ALT) elevation, and aspartate aminotransferase (AST) elevation. The methodological quality of studies was evaluated using the Cochrane collaboration risk of bias tool. RevMan 5.3 software and R software was used in meta-analysis and the effect values were expressed as relative risk ( RR) and its 95% confidence interval ( CI). Results:A total of 5 RCTs (2 for non-small cell lung cancer, 2 for small cell lung cancer, and 1 for metastatic melanoma) were entered in this study, involving 2 532 patients, in which 1 335 patients were in the trial group and 1 197 patients in the control group. The results of quality evaluation showed that 5 RCTs were all high-quality studies. The results of meta-analysis showed that the incidences of treatment-related grade 1-5 AEs and grade 3-5 AEs in the trial group were significantly higher than those in the control group [87.27% (1 165/1 335) vs. 82.04% (982/1 197), RR=1.07, 95 %CI: 1.03-1.10, P<0.001; 50.26% (671/1 335) vs. 37.68% (451/1 197), RR=1.40, 95 %CI: 1.07-1.82, P=0.010]. However, the results of subgroup analysis showed that the difference in incidences of treatment-related grade 1-5 AEs and grade 3-5 AEs were statistically significant only in patients with metastatic melanoma between the trial group and the control group [98.79% (244/247) vs. 94.02% (236/251), RR=1.05, 95 %CI: 1.02-1.09, P=0.005; 56.28%(139/247) vs. 27.89%(70/251), RR=2.02, 95 %CI: 1.61-2.53, P<0.001]. The analysis of common AEs showed that the risks of rash, diarrhea, and liver injury increased in the trial group (all P<0.05) and the difference in treatment-related death between the 2 groups was not statistically significant [1.05%(14/1 335) vs. 0.42%(5/1 197), χ2=3.374, P=0.066]. Conclusion:The risk of AEs in patients with advanced solid tumors treated with combination of ipilimumab and chemotherapy is higher than that with chemotherapy alone, especially the immune-related AEs, which deserves clinical vigilance.
