Objectives. Recent trials have shown an overall survival (OS) benefit in 10-40% advanced cancer patients treated with programmed cell death 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors. Here, we aimed to evaluate the relationship between PD-L1 expression and the therapeutic efficacy of PD-1 or PD-L1 inhibitors in patients with cancer with recurrent or metastatic disease, compared with control treatments. Methods. We systematically searched Medline (PubMed), Embase, and Cochrane Library databases up to Jan 2019 and pooled the treatment effects (hazard ratio or relative ratio) of PD-1/PD-L1 inhibitors in patients with different PD-L1 expression. Results. Overall, twenty-four qualifying trials with over 14,860 subjects were eligible in this study. Compared with conventional agents, anti-PD/PD-L1 drugs significantly reduced the risk of death (hazard ratio 0.72, 95% CI 0.66 to 0.78), irrespective of the tumor type. Additionally, when PD-L1 expression ≥1% was defined as positive, anti-PD-1/PD-L1 monotherapy correlated with prolonged overall survival in patients with nonsmall cell lung cancer (NSCLC) (0.72, 0.61 to 0.86) and other cancer types (0.66, 0.57 to 0.76) patients with PD-L1 positive, rather than those with PD-L1 negative (hazard ratio for NSCLC and other cancer types: 0.84 and 0.87, respectively; all ). The subgroup analyses to experimental agents, PD-1/PD-L1 inhibitors, PD-L1 antibody clone, and type of IHC scoring method validated the robustness of these findings. However, anti-PD-1/PD-L1 combination therapies can reduce the risk of death for patients with different cancer types, regardless of PD-L1 expression ( for all PD-L1 expression status). Conclusions. We recommend PD-L1 expression as a predictive biomarker in patient selection for anti-PD-1/PD-L1 monotherapy, but not for combination therapies.

中文翻译：

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PD-L1 表达在预测癌症患者抗 PD-1 或​​抗 PD-L1 治疗疗效中的价值：系统评价和荟萃分析

目标。最近的试验表明，接受程序性细胞死亡 1 (PD-1) 或程序性死亡配体 1 (PD-L1) 抑制剂治疗的 10-40% 晚期癌症患者的总生存期 (OS) 获益。在这里，我们旨在评估与对照治疗相比，PD-L1 表达与 PD-1 或​​ PD-L1 抑制剂在患有复发性或转移性疾病的癌症患者中的治疗效果之间的关系。方法。我们系统检索了截至 2019 年 1 月的 Medline (PubMed)、Embase 和 Cochrane Library 数据库，并汇总了 PD-1/PD-L1 抑制剂在不同 PD-L1 表达患者中的治疗效果（风险比或相对比）。结果. 总体而言，本研究中有超过 14,860 名受试者的 24 项合格试验符合条件。与传统药物相比，无论肿瘤类型如何，抗 PD/PD-L1 药物都显着降低了死亡风险（风险比 0.72，95% CI 0.66 至 0.78）。此外，当 PD-L1 表达≥1% 被定义为阳性时，抗 PD-1/PD-L1 单药治疗与非小细胞肺癌 (NSCLC) (0.72, 0.61 至 0.86) 和其他癌症患者的总生存期延长相关PD-L1 阳性的患者类型（0.66, 0.57 至 0.76），而不是 PD-L1 阴性的患者（NSCLC 和其他癌症类型的风险比：分别为 0.84 和 0.87；所有）。对实验药物、PD-1/PD-L1 抑制剂、PD-L1 抗体克隆和 IHC 评分方法类型的亚组分析验证了这些发现的稳健性。然而，无论 PD-L1 表达如何，抗 PD-1/PD-L1 联合疗法都可以降低不同癌症类型患者的死亡风险。对于所有 PD-L1 表达状态）。结论。我们建议将 PD-L1 表达作为抗 PD-1/PD-L1 单药治疗患者选择的预测性生物标志物，但不适用于联合治疗。