比较 PD-1 与 PD-L1 抑制剂在非小细胞肺癌中的毒性特征：文献系统分析。
Comparison of the toxicity profile of PD-1 versus PD-L1 inhibitors in non-small cell lung cancer: A systematic analysis of the literature.
机构信息
Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia.
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University, Atlanta, Georgia.
出版信息
Cancer. 2018 Jan 15;124(2):271-277. doi: 10.1002/cncr.31043. Epub 2017 Sep 28.
BACKGROUND
Monoclonal antibodies against programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) are effective therapies in patients with non-small cell lung cancer (NSCLC). Herein, the authors performed a systematic review investigating differences in the toxicities of PD-1 and PD-L1 inhibitors.
METHODS
An electronic literature search was performed of public databases (MEDLINE, Excerpta Medica dataBASE [EMBASE], and Cochrane) and conference proceedings for trials using PD-1 inhibitors (nivolumab and pembrolizumab) and PD-L1 inhibitors (atezolizumab, durvalumab, and avelumab) in patients with NSCLC. A formal systematic analysis was conducted with Comprehensive Meta-Analysis software (version 2.2). Clinical and demographic characteristics, response, and toxicity data were compared between both groups.
RESULTS
A total of 23 studies reported between 2013 and 2016 were eligible for analysis. The total number of patients evaluated for toxicities was 3284 patients in the PD-1 group and 2460 patients in the PD-L1 group. The baseline patient characteristics of the 2 groups were similar, although there was a trend toward increased squamous histology in the group treated with PD-L1 (32% vs 25%; P = .6). There was no difference in response rate noted between PD-1 (19%) and PD-L1 (18.6%) inhibitors (P = .17). The incidence of overall adverse events (AEs) was comparable between the PD-1 and PD-L1 inhibitors (64% [95% confidence interval (95% CI), 63%-66%] vs 66% [95% CI, 65%-69%]; P = .8). Fatigue was the most frequently reported AE with both classes of drugs. Patients treated with PD-1 inhibitors were found to have a slightly increased rate of immune-related AEs (16% [95% CI, 14%-17%] vs 11% [95% CI, 10%-13%]; P = .07) and pneumonitis (4% [95% CI, 3%-5%] vs 2% [95% CI, 1%-3%]; P = .01) compared with patients who received PD-L1 inhibitors.
CONCLUSIONS
In this systematic review involving 5744 patients with NSCLC, the toxicity and efficacy profiles of PD-1 and PD-L1 inhibitors appear to be similar. Cancer 2018;124:271-7. © 2017 American Cancer Society.
背景
程序性细胞死亡蛋白 1（PD-1）和程序性死亡配体 1（PD-L1）的单克隆抗体在非小细胞肺癌（NSCLC）患者中是有效的治疗方法。在此，作者进行了一项系统评价，以研究 PD-1 和 PD-L1 抑制剂毒性的差异。
方法
对公共数据库（MEDLINE、Excerpta Medica dataBASE [EMBASE]和 Cochrane）和临床试验会议记录进行了电子文献检索，以评估用于 NSCLC 患者的 PD-1 抑制剂（nivolumab 和 pembrolizumab）和 PD-L1 抑制剂（atezolizumab、durvalumab 和 avelumab）的试验。使用 Comprehensive Meta-Analysis 软件（版本 2.2）进行了正式的系统分析。比较了两组患者的临床和人口统计学特征、反应和毒性数据。
结果
2013 年至 2016 年期间共进行了 23 项研究，其中有 23 项研究符合分析条件。在 PD-1 组中，有 3284 名患者评估了毒性，在 PD-L1 组中，有 2460 名患者评估了毒性。两组患者的基线特征相似，但 PD-L1 组的鳞状组织学比例有增加趋势（32%比 25%；P =.6）。PD-1（19%）和 PD-L1（18.6%）抑制剂之间的反应率无差异（P =.17）。PD-1 和 PD-L1 抑制剂的总体不良事件（AE）发生率相似（64%[95%置信区间（95%CI），63%-66%]比 66%[95%CI，65%-69%]；P =.8）。疲乏是两种药物最常报告的 AE。与接受 PD-L1 抑制剂治疗的患者相比，接受 PD-1 抑制剂治疗的患者免疫相关 AE 的发生率略有增加（16%[95%CI，14%-17%]比 11%[95%CI，10%-13%]；P =.07）和肺炎（4%[95%CI，3%-5%]比 2%[95%CI，1%-3%]；P =.01）。
结论
在这项涉及 5744 名 NSCLC 患者的系统评价中，PD-1 和 PD-L1 抑制剂的毒性和疗效谱似乎相似。癌症 2018;124:271-7. © 2017 美国癌症协会。
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