Fahmy Omar, Ahmed Osama A A, Khairul-Asri Mohd Ghani, Alhakamy Nabil A, Alharbi Waleed S, Fahmy Usama A, El-Moselhy Mohamed A, Fresta Claudia G, Caruso Giuseppe, Caraci Filippo
Department of Urology, Universiti Putra Malaysia, Selangor 43400, Malaysia.
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Biomedicines. 2022 May 10;10(5):1101. doi: 10.3390/biomedicines10051101.
Background: Recently, the combination of durvalumab and tremelimumab, two immune checkpoint inhibitors, for the treatment of different types of cancers has been considered; however, its overall effects, including its safety, are still unclear and need to be further investigated. Objectives: The aim of the present systematic review and meta-analysis was to investigate the safety and tolerability of this combination of drugs. Methods: A systematic review of the literature, based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, was conducted by employing online electronic databases and the American Society of Clinical Oncology (ASCO) Meeting Library. The selection of eligible publications was made following a staged screening and selection process. The software RevMan 5.4 was used to run the quantitative analysis and forest plots, while the Cochrane tool was employed for risk of bias assessment. Results: From the retrieved 157 results, 9 randomized controlled trials involving 3060 patients were included. By comparing the combination of durvalumab and tremelimumab vs. durvalumab monotherapy, it was observed that: adverse events (AEs) ≥ Grade 3 incidence was 32.6% (536/1646) vs. 23.8% (336/1414) (Z = 2.80; p = 0.005; risk ratio (RR) = 1.44), reduced appetite incidence was 10.8% (154/1427) vs. 8.3% (108/1305) (Z = 2.26; p = 0.02; RR = 1.31), diarrhea was reported in 15.6% (229/1473) vs. 8.1% (110/1352) (Z = 5.90; p < 0.00001; RR = 1.91), rash incidence was equal to 11.1% (160/1441) vs. 6.5% (86/1320) (Z = 4.35; p <0.0001; RR = 1.75), pruritis was 13.6% (201/1473) vs. 7.7% (104/1352) (Z = 5.35; p < 0.00001; RR = 1.83), fever was 10.5% (42/399) vs. 6.6% (22/330) (Z = 2.27; p = 0.02; RR = 1.77), discontinuation rate was 18% (91/504) vs. 3% (36/434) (Z = 4.78; p < 0.00001; RR = 2.41), and death rate was 2.6% (13/504) vs. 0.7% (3/434) (Z = 1.90; p = 0.06; RR = 2.77). Conclusions: It was observed that the combined (durvalumab and tremelimumab) vs. monotherapy (durvalumab) is associated with a higher risk of treatment discontinuation, mortality, fever, diarrhea, rash, pruritis, and reduced appetite. This information is relevant and should be disclosed, especially to patients that are currently enrolled in clinical trials considering this combined therapy.
最近，两种免疫检查点抑制剂度伐利尤单抗和曲美木单抗联合用于治疗不同类型癌症的方案已被纳入考虑范围；然而，其总体疗效，包括安全性，仍不明确，需要进一步研究。目的：本系统评价和荟萃分析的目的是研究这种联合用药方案的安全性和耐受性。方法：基于系统评价和荟萃分析的首选报告项目（PRISMA）声明，通过在线电子数据库和美国临床肿瘤学会（ASCO）会议图书馆对文献进行系统评价。通过分阶段筛选和选择过程来选择符合条件的出版物。使用RevMan 5.4软件进行定量分析和绘制森林图，同时采用Cochrane工具进行偏倚风险评估。结果：从检索到的157个结果中，纳入了9项涉及3060例患者的随机对照试验。通过比较度伐利尤单抗和曲美木单抗联合用药与度伐利尤单抗单药治疗，观察到：≥3级不良事件（AE）发生率为32.6%（536/1646），而单药治疗组为23.8%（336/1414）（Z = 2.80；p = 0.005；风险比（RR）= 1.44），食欲减退发生率为10.8%（154/1427），而单药治疗组为8.3%（108/1305）（Z = 2.26；p = 0.02；RR = 1.31），腹泻报告率为15.6%（229/1473），而单药治疗组为8.1%（110/1352）（Z = 5.90；p < 0.00001；RR = 1.91），皮疹发生率为11.1%（160/1441），而单药治疗组为6.5%（86/1320）（Z = 4.35；p <0.0001；RR = 1.75），瘙痒发生率为13.6%（201/1473），而单药治疗组为7.7%（104/1352）（Z = 5.35；p < 0.00001；RR = 1.8
