Indirect comparison between immunotherapy alone and immunotherapy plus chemotherapy as first-line treatment for advanced non-small cell lung cancer: A systematic review

Objectives: Use of immune checkpoint inhibitors (ICIs) as first-line
treatment for advanced (stage IIIB/IV) non-small cell lung cancer (NSCLC)
remains controversial. Clinical trials comparing single-drug immunotherapy
(IO) with immunotherapy plus chemotherapy (IC) are lacking. We aimed to
compare the efficacy of IO alone with that of IC as first-line treatment
for advanced NSCLC. Design: Systematic review Data sources: PubMed, the
Cochrane Library, and Embase for related studies on NSCLC;
ClinicalTrials.gov, American Society of Clinical Oncology Meeting Library,
and World Conference on Lung Cancer for relevant conference abstracts.
Eligibility criteria: Articles meeting the following criteria were
selected: (1) randomized controlled trials on NSCLC treatment, (2) all
individuals in the studies had not received treatment previously, and (3)
research on IO monotherapy using programmed death-1/programmed death
ligand-1 (PD-L1) inhibitors or IC. Data extraction and synthesis: After
reading the original literature, two reviewers independently extracted the
relevant information. The primary outcomes were progression-free survival
(PFS), overall survival (OS), and objective response rate (ORR). We also
extracted data on treatment-related adverse events and immune-related
adverse events (irAEs). Results: Overall, 10 randomized controlled
clinical trials (n = 5765) were included. As first-line treatment for
advanced NSCLC, IC tended to yield better PFS, OS, and ORR than did IO.
Furthermore, IC yielded significantly better PFS than IO when tumor PD-L1
expression was at least 50% (HR: 1.81, 95% CI: 1.18–2.78) and yielded a
better OS and PFS when tumor PD-L1 expression was at least 1%; IO resulted
in fewer adverse events than did IC. However, the incidence of irAEs was
higher for IO than for IC. Conclusions: The findings of the indirect
comparison indicate that IC as first-line treatment for advanced NSCLC is
significantly more effective than IO in patients with PD-L1 expression in
at least 50% of tumor cells.

研究目的：免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）作为晚期（IIIB/IV期）非小细胞肺癌（non-small cell lung cancer, NSCLC）的一线治疗方案仍存在争议。目前尚无针对单药免疫治疗（IO）与免疫联合化疗（IC）的头对头临床试验。本研究旨在对比IO单药与IC方案作为晚期NSCLC一线治疗的临床疗效。
研究设计：系统综述。
数据来源：检索PubMed、Cochrane图书馆及Embase数据库，获取NSCLC相关研究；检索ClinicalTrials.gov、美国临床肿瘤学会会议文库及世界肺癌大会，获取相关会议摘要。
纳入标准：选取符合以下全部条件的文献：(1) 针对NSCLC治疗的随机对照试验；(2) 研究纳入的所有受试者均未接受过系统抗肿瘤治疗；(3) 研究涉及使用程序性死亡蛋白-1/程序性死亡蛋白配体-1（programmed death-1/programmed death ligand-1, PD-L1）抑制剂的IO单药治疗或IC联合治疗方案。
数据提取与合成：由两名研究者独立阅读原始文献后提取相关研究信息。主要结局指标为无进展生存期（progression-free survival, PFS）、总生存期（overall survival, OS）及客观缓解率（objective response rate, ORR）。同时提取治疗相关不良事件与免疫相关不良事件（immune-related adverse events, irAEs）的相关数据。
结果：最终纳入10项随机对照临床试验，合计5765例受试者。作为晚期NSCLC的一线治疗方案，IC方案相较IO单药可获得更优的无进展生存期、总生存期及客观缓解率。亚组分析显示，当肿瘤PD-L1表达≥50%时，IC方案的无进展生存期显著优于IO单药（风险比：1.81，95%置信区间：1.18~2.78）；当肿瘤PD-L1表达≥1%时，IC方案的总生存期与无进展生存期均更优；IO单药的总体不良事件发生率低于IC方案，但免疫相关不良事件的发生率更高。
结论：本间接比较研究结果表明，对于肿瘤细胞PD-L1表达≥50%的晚期NSCLC患者，IC方案作为一线治疗的临床疗效显著优于IO单药。