免疫检查点抑制剂联合化疗作为广泛期小细胞肺癌一线治疗的疗效和安全性：基于混合效应模型的荟萃分析
Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy as first-line treatment for extensive-stage small cell lung cancer: a meta-analysis based on mixed-effect models.
作者信息
Zheng Jianqing, Deng Yujie, Huang Bifen, Chen Xiaohui
机构信息
Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
Department of Medical Oncology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
出版信息
Front Med (Lausanne). 2023 Jul 31;10:1198950. doi: 10.3389/fmed.2023.1198950. eCollection 2023.
BACKGROUND
Extensive-stage small cell lung cancer (ES-SCLC) is a highly invasive and fatal disease with limited therapeutic options and poor prognosis. Our study aims to systematically evaluate the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy (ICIs+ChT) vs. chemotherapy alone (ChT) in the first-line treatment of ES-SCLC.
METHODS
A literature search was performed for randomized controlled trials (RCTs) related to "ICIs+ChT" vs. "ChT" in the first-line treatment of ES-SCLC in PubMed, Cochrane Library, Embase, CNKI, and other databases. RevMan 5.4 software was used to perform meta-analyses with hazard ratio (HR) and relative risk (RR). SAS 9.4 software was applied to conduct a mixed-effect model meta-analysis of the survival outcomes and draw survival curves.
RESULTS
A total of 2,638 patients with ES-SCLC from 6 RCTs were included, of which 1,341 patients received "ICIs+ChT" and 1,297 received ChT. Based on the meta-analysis results provided by the mixed-effect model, patients receiving the "ICIs+ChT" regimen had a significantly longer overall survival (OS, HR = 0.800, 95% CI = 0.731-0.876, < 0.001) and progression-free survival (PFS, HR = 0.815, 95% CI = 0.757-0.878, <0.001) in comparison to those receiving ChT only. Compared with ChT, "ICIs+ChT" did neither improve the objective response rate (ORR, RR = 1.06, 95% CI = 1.00-1.12, = 0.06) nor did it improve the disease control rate (DCR, RR = 0.97, 95% CI = 0.92-1.03, = 0.35). Although the incidence of grade 3 to 5 treatment-related adverse events (trAEs) in the "ICIs+ChT" subgroup did not increase (RR = 1.16, 95% CI = 0.97-1.39, = 0.11), the incidence of grade 3 to 5 immune-related adverse events (irAEs) increased significantly (RR = 4.29, 95% CI = 1.73-10.61, < 0.00001).
CONCLUSION
ICIs+ChT regimen could significantly prolong OS and PFS in patients with ES-SCLC compared with ChT alone. Although the incidence of irAEs in "ICIs+ChT" is higher than that in the "ChT" subgroup, the incidence of trAEs is similar within the two subgroups. ICIs combined with chemotherapy demonstrated a good choice as first-line treatment for ES-SCLC.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier: CRD42022348496.
背景
广泛期小细胞肺癌（ES-SCLC）是一种侵袭性很强的致命疾病，治疗选择有限，预后较差。我们的研究旨在系统评估免疫检查点抑制剂联合化疗（ICIs+ChT）与单纯化疗（ChT）在ES-SCLC一线治疗中的疗效和安全性。
方法
在PubMed、Cochrane图书馆、Embase、中国知网等数据库中检索与ES-SCLC一线治疗中“ICIs+ChT”对比“ChT”相关的随机对照试验（RCT）。使用RevMan 5.4软件进行以风险比（HR）和相对风险（RR）为指标的荟萃分析。应用SAS 9.4软件对生存结局进行混合效应模型荟萃分析并绘制生存曲线。
结果
共纳入6项RCT中的2638例ES-SCLC患者，其中1341例接受“ICIs+ChT”治疗，1297例接受ChT治疗。基于混合效应模型提供的荟萃分析结果，与仅接受ChT治疗的患者相比，接受“ICIs+ChT”方案的患者总生存期（OS，HR = 0.800，95%CI = 0.731-0.876，P<0.001）和无进展生存期（PFS，HR = 0.815，95%CI = 0.757-0.878，P<0.001）显著更长。与ChT相比，“ICIs+ChT”既未提高客观缓解率（ORR，RR = 1.06，95%CI = 1.00-1.12，P = 0.06），也未提高疾病控制率（DCR，RR = 0.97，95%CI = 0.92-1.03，P = 0.35）。尽管“ICIs+ChT”亚组中3至5级治疗相关不良事件（trAEs）的发生率没有增加（RR = 1.16，95%CI = 0.97-1.39，P = 0.11），但3至5级免疫相关不良事件（irAEs）的发生率显著增加（RR = 4.29，95%CI = 1.73-10.61，P<0.00001）。
结论
与单纯ChT相比，ICIs+ChT方案可显著延长ES-SCLC患者的OS和PFS。尽管“ICIs+ChT”中irAEs的发生率高于“ChT”亚组，但两个亚组中trAEs的发生率相似。ICIs联合化疗是ES-SCLC一线治疗的良好选择。
系统评价注册
PROSPERO，标识符：CRD42022348496。
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