Background Immune checkpoint inhibitors (ICIs) have shown remarkable therapeutic outcomes among cancer patients. Durvalumab plus tremelimumab (DT) is under investigation as a new ICI combination therapy, and its efficacy has been reported in various types of cancer. However, the safety profile of DT remains unclear, especially considering rare adverse events (AEs). Objective We aimed to assess the frequency of AEs associated with DT. Design This study type is a systematic review and meta-analysis. Data Sources and Methods Four databases were searched for articles. Randomized trials, single-arm trials, and prospective and retrospective observational studies were included. The type of cancer, previous treatment, and performance status were not questioned. Major AE indicators such as any AE and the pooled frequency of each specific AE were used as outcomes. As a subgroup analysis, we also compared cases in which DT was performed as first-line treatment with those in which it was performed as second-line or later treatment. The protocol for this systematic review was registered on the University Hospital Medical Information Network (UMIN) Center website (ID: UMIN000046751). Results Forty-one populations including 3099 patients were selected from 30 articles. Pooled frequencies of key AE indicators are shown below: any AEs, 77.8% [95% confidence interval (CI): 67.9-87.6]; grade ⩾ 3 AEs, 29.3% (95% CI: 24.2-34.4); serious AEs, 34.9% (95% CI: 28.1-41.7); AE leading to discontinuation, 13.3% (95% CI: 9.3-17.4); treatment-related deaths, 0.98% (95% CI: 0.5-1.5). AEs with a frequency exceeding 15% are shown below: fatigue, 30.1% (95% CI: 23.8-36.3); diarrhea, 21.7% (95% CI: 17.8-25.6); pruritus 17.9% (95% CI: 14.4-21.3); decreased appetite, 17.7% (95% CI: 13.7-22.0); nausea, 15.6% (95% CI: 12.1-19.6). There were no significant differences in these pooled frequencies between subgroups. Conclusions The incidence of any AE in DT therapy was approximately 78%, and the incidence of grade 3 or higher AEs was approximately 30%, which was independent of prior therapy.

中文翻译：

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durvalumab 和 tremelimumab 联合方案引起的不良事件：系统评价和荟萃分析。

背景 免疫检查点抑制剂（ICIs）在癌症患者中显示出显着的治疗效果。Durvalumab 联合 tremelimumab (DT) 作为一种新的 ICI 联合疗法正在接受研究，其疗效已在多种类型的癌症中得到报道。然而，DT 的安全性仍不清楚，特别是考虑到罕见的不良事件 (AE)。目的 我们旨在评估与 DT 相关的 AE 发生频率。设计 这种研究类型是系统评价和荟萃分析。数据来源和方法 在四个数据库中搜索了文章。包括随机试验、单臂试验以及前瞻性和回顾性观察研究。癌症类型、既往治疗和表现状态均未受到质疑。主要 AE 指标（例如任何 AE 和每个特定 AE 的汇总频率）被用作结果。作为亚组分析，我们还比较了 DT 作为一线治疗与二线或后续治疗的病例。本系统评价的方案已在大学医院医学信息网络 (UMIN) 中心网站上注册（ID：UMIN000046751）。结果从30篇文章中筛选出41个人群，包括3099名患者。关键 AE 指标的汇总频率如下所示： 任何 AE，77.8% [95% 置信区间 (CI)：67.9-87.6]；⩾ 3 级 AE，29.3%（95% CI：24.2-34.4）；严重 AE，34.9%（95% CI：28.1-41.7）；导致停药的 AE，13.3%（95% CI：9.3-17.4）；治疗相关死亡，0.98%（95% CI：0.5-1.5）。频率超过 15% 的 AE 如下所示： 疲劳，30.1%（95% CI：23.8-36.3）；腹泻，21.7%（95% CI：17.8-25.6）；瘙痒 17.9% (95% CI: 14.4-21.3)；食欲下降，17.7%（95% CI：13.7-22.0）；恶心，15.6%（95% CI：12.1-19.6）。亚组之间的这些汇总频率没有显着差异。结论 DT 治疗中任何 AE 的发生率约为 78%，3 级或以上 AE 的发生率约为 30%，与既往治疗无关。