School of Public Health, Weifang Medical University, Weifang, China.
Eur Rev Med Pharmacol Sci. 2021 Apr;25(7):2866-2884. doi: 10.26355/eurrev_202104_25541.
PD-1/PD-L1 inhibitors are a relatively new class of immunotherapeutic drugs approved for advanced non-small-cell lung cancer. The purpose of this study was to conduct a network meta-analysis to compare the safety and efficacy of these immune checkpoint inhibitors (ICIs).
We used Bayesian network meta-analysis methods to evaluate the efficacy and safety of the included treatments. We further analyzed subgroups based on PD-L1 expression level, histology type, and line of the treatment setting.
We identified 19 RCTs, including 12,753 patients. In the analysis of all-comers, the pembrolizumab/chemotherapy combination ranked best for overall survival (OS) and progression-free survival (PFS). Durvalumab was the only ICI treatment that showed no benefit over chemotherapy. In the first-line setting only, in terms of OS, atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab ranked as the best treatments for patients with PD-L1 expression levels of ≥50%, 1-49%, and <1%, respectively. Nivolumab, atezolizumab, pembrolizumab, and durvalumab all had lower odds of grade 3 or greater treatment-related adverse events (TRAEs) compared to chemotherapy. With the addition of chemotherapy to any ICI regimen, the odds of TRAEs increased in a considerable and statistically significant way.
While the pembrolizumab/chemotherapy combination was the most effective therapy in the overall cohort of all-comers, treatment preferences varied by treatment-line setting, tumor characteristics, and outcome of interest. In the first-line setting, the most effective treatments for patients with PD-L1 expressions of ≥50%, 1-49%, and <1% were atezolizumab, pembrolizumab/chemotherapy, and nivolumab/ipilimumab, respectively.
PD-1/PD-L1 抑制剂是一类新的免疫治疗药物，已被批准用于晚期非小细胞肺癌。本研究旨在进行网络荟萃分析，比较这些免疫检查点抑制剂（ICIs）的安全性和疗效。
我们使用贝叶斯网络荟萃分析方法评估纳入治疗的疗效和安全性。我们进一步根据 PD-L1 表达水平、组织学类型和治疗线进行亚组分析。
我们确定了 19 项 RCT，共纳入 12753 名患者。在所有患者分析中，pembrolizumab/化疗联合治疗在总生存期（OS）和无进展生存期（PFS）方面表现最佳。度伐利尤单抗是唯一一种与化疗相比没有获益的 ICI 治疗药物。仅在一线治疗中，在 OS 方面，对于 PD-L1 表达水平≥50%、1-49%和<1%的患者，atezolizumab、pembrolizumab/化疗和 nivolumab/ipilimumab 分别为最佳治疗药物。与化疗相比，nivolumab、atezolizumab、pembrolizumab 和 durvalumab 发生 3 级或更高级别的治疗相关不良事件（TRAEs）的可能性更低。在任何 ICI 方案中添加化疗，TRAEs 的发生几率会显著增加。
虽然 pembrolizumab/化疗联合治疗在所有患者的总体队列中是最有效的治疗方法，但治疗偏好因治疗线设置、肿瘤特征和关注的结局而异。在一线治疗中，对于 PD-L1 表达水平≥50%、1-49%和<1%的患者，最有效的治疗药物分别为 atezolizumab、pembrolizumab/化疗和 nivolumab/ipilimumab。
