Department of Hematology/Medical Oncology, Atlanta VA Medical Center, Decatur, GA 30033, United States; Winship Cancer Institute of Emory University, Atlanta, GA 30322, United States.
Georgia Cancer Center, Medical College of Georgia at Augusta University, Augusta, GA 30912, United States.
Crit Rev Oncol Hematol. 2017 Nov;119:1-12. doi: 10.1016/j.critrevonc.2017.09.002. Epub 2017 Sep 8.
Targeting immune checkpoints is a novel approach in cancer therapy. This strategy may trigger immune related adverse events (irAE). We hypothesize that the incidence of irAE will be greater in patients receiving immune checkpoint inhibitors (ICI) targeting only immune cells compared to those that also target tumor cells (PD-L1). In addition, we compared the specific irAE profile and overall response rate (ORR) for each ICI by target(s).
We reviewed all ICI cancer clinical trials (90; 174 arms) that reported irAE and were published through MEDLINE. 114 arms from 73 trials were eligible for this meta-analysis (including 11,328 patients). We collected and compared arm-specific data including ICI target, number of patients with irAE of any grade, grade 3+ and grade 5, specific irAE, and ORR. The R package "meta" was used to conduct a meta-analysis to calculate and compare the percentage of patients with irAE and ORR.
The incidence (% of patients) of any grade irAE per ICI target was reported for 40 arms (3418 patients) treated with ICI. Most arms (80%) and patients (53%) studied were on phase 1/2 clinical trials. Patients were treated for solid malignancy on 39 arms (97%), mainly melanoma (40%). Two arms included ICI combinations. The incidence of any grade irAE was higher in patients who received ICI targeting CTLA-4 (53.8%) than PD-1 (26.5%) and PD-L1 ICI (17.1%) (P<0.001). Comparative specific irAE rates were calculated for each ICI target.
Our systematic review supported our mechanistic-driven hypothesis. We encourage investigators to report the incidence of irAE in future ICI combination trials.
靶向免疫检查点是癌症治疗的一种新方法。这种策略可能会引发免疫相关不良反应（irAE）。我们假设，与仅靶向免疫细胞的免疫检查点抑制剂（ICI）相比，同时靶向肿瘤细胞的 ICI（PD-L1）的患者发生 irAE 的概率更高。此外，我们比较了每种 ICI 按靶点的特定 irAE 谱和总缓解率（ORR）。
我们回顾了通过 MEDLINE 发表的所有报告 irAE 的 ICI 癌症临床试验（90 项；174 个臂）。73 项试验中有 114 个臂符合这项荟萃分析的条件（包括 11328 名患者）。我们收集并比较了臂特异性数据，包括 ICI 靶点、任何级别 irAE 的患者数量、3+级和 5 级、特定 irAE 和 ORR。使用 R 包“meta”进行荟萃分析，以计算和比较 irAE 和 ORR 的患者百分比。
报告了 40 个臂（3418 名患者）接受 ICI 治疗时每个 ICI 靶点的任何级别 irAE 的发生率（患者百分比）。大多数臂（80%）和患者（53%）处于 1/2 期临床试验。39 个臂（97%）治疗实体恶性肿瘤，主要是黑色素瘤（40%）。有两个臂包括 ICI 联合治疗。接受 CTLA-4 靶向 ICI（53.8%）治疗的患者发生任何级别 irAE 的概率高于 PD-1（26.5%）和 PD-L1 ICI（17.1%）（P<0.001）。为每个 ICI 靶点计算了比较特定 irAE 率。
我们的系统综述支持了我们的基于机制的假设。我们鼓励研究人员在未来的 ICI 联合试验中报告 irAE 的发生率。
