联合 PD-1/PD-L1 抑制剂和胸部放疗治疗非小细胞肺癌的毒性特征：系统评价。
Toxicity Profile of Combining PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy in Non-Small Cell Lung Cancer: A Systematic Review.
机构信息
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China.
Department of Otorhinolaryngology & Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
出版信息
Front Immunol. 2021 Mar 30;12:627197. doi: 10.3389/fimmu.2021.627197. eCollection 2021.
BACKGROUND
The combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.
METHODS
An electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.
RESULTS
Eleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.
CONCLUSION
Most AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.
背景
免疫检查点抑制剂（ICI）联合胸部放疗（TRT）在非小细胞肺癌（NSCLC）患者中显示出显著的临床疗效。然而，目前关于不良反应（AE）的数据来自于前瞻性临床试验或回顾性研究中纳入的一小部分患者。因此，我们进行了这项系统评价，以确定这种联合治疗相关的 AE。
方法
在评估 NSCLC 患者ICI 联合 TRT 的前瞻性临床试验数据库和会议论文集上进行了电子文献检索。进行了系统分析，以确定联合治疗的 AE 特征和发生率。我们进一步比较了程序性死亡受体 1（PD-1）和程序性死亡配体 1（PD-L1）抑制剂的 AE，以及 ICI 和 TRT 的序贯和同时给药，以帮助识别高危患者。使用 Review Manager（版本 5.3；The Cochrane Collaboration，英国牛津）和 Stata 版本 12.0（StataCorp，德克萨斯州立大学，美国）软件进行了系统分析。
结果
11 项涉及 NSCLC 患者 1113 人的临床试验符合分析条件。所有级别 AE 的发生率为 95.5%；高等级 AE（等级≥3）的发生率为 30.2%。最常见的所有级别 AE 是疲劳（49.7%），而肺炎是最常见的高等级 AE（3.8%）和 5 级 AE（0.6%）。值得注意的是，PD-1 和 PD-L1 抑制剂的毒性谱相似。与序贯治疗相比，同时治疗与更高等级 AE（41.6%比 24.8%，P=0.17）和肺炎（7.1%比 3.9%，P=0.14）的发生率更高，但无显著差异。
结论
这种联合治疗的大多数 AE 是可以耐受的；作为最常见的高等级 AE，肺炎需要医生的高度重视。接受 PD-1 或 PD-L1 治疗的患者的毒性谱相似，同时治疗和序贯治疗之间无显著差异。
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