Matsumoto Hiromi, Somekawa Kohei, Horita Nobuyuki, Ueda Suguru, Kaneko Megumi, Kaneko Ayami, Fukuda Nobuhiko, Izawa Ami, Kamimaki Chisato, Tanaka Katsushi, Murohashi Kota, Fuji Hiroaki, Tagami Yoichi, Aoki Ayako, Watanabe Keisuke, Hara Yu, Kobayashi Nobuaki, Kaneko Takeshi
Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Chemotherapy Center, Yokohama City University Hospital, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Ther Adv Med Oncol. 2023 Sep 13;15:17588359231198453. doi: 10.1177/17588359231198453. eCollection 2023.
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).
We aimed to assess the frequency of AEs associated with DT.
This study type is a systematic review and meta-analysis.
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).
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.
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.
免疫检查点抑制剂（ICI）在癌症患者中已显示出显著的治疗效果。度伐利尤单抗联合曲美木单抗（DT）作为一种新的ICI联合疗法正在研究中，其疗效已在多种癌症类型中报道。然而，DT的安全性概况仍不明确，尤其是考虑到罕见不良事件（AE）。
我们旨在评估与DT相关的AE发生频率。
本研究类型为系统评价和荟萃分析。
检索四个数据库中的文章。纳入随机试验、单臂试验以及前瞻性和回顾性观察性研究。癌症类型、既往治疗和体能状态不作限制。主要AE指标如任何AE以及各特定AE的合并发生频率用作结局指标。作为亚组分析，我们还比较了DT作为一线治疗与作为二线或更晚治疗的病例。本系统评价的方案已在大学医院医学信息网络（UMIN）中心网站注册（ID：UMIN000046751）。
从30篇文章中选取了包括3099例患者的41个研究对象。关键AE指标的合并发生频率如下：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）。发生频率超过15%的AE如下：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）；食欲减退，17.7%（95%CI：13.7 - 22.0）；恶心，15.6%（95%CI：12.1 - 19.6）。这些合并发生频率在亚组之间无显著差异。
DT治疗中任何AE的发生率约为78%，3级或更高等级AE的发生率约为30%，且与既往治疗无关。
