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。目前尚无单药免疫治疗（immunotherapy, IO）与免疫联合化疗（immunotherapy plus chemotherapy, IC）的头对头临床试验对比数据。本研究旨在比较单药IO与IC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数据库中与NSCLC相关的研究；同时检索ClinicalTrials.gov、美国临床肿瘤学会会议文库及世界肺癌大会会议摘要库，获取相关会议摘要资料。

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既往抗肿瘤治疗；（3）研究内容为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）抑制剂的单药IO治疗或IC治疗。

数据提取与合成：由两名评价员独立阅读原始文献后，分别提取相关研究信息。本研究的主要结局指标包括无进展生存期（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。

研究结果：最终纳入10项随机对照临床试验，合计5765例受试者。对于晚期NSCLC的一线治疗，相较单药IO，IC方案在PFS、OS及ORR上均呈现更优趋势。亚组分析显示，当肿瘤PD-L1表达水平≥50%时，IC方案的PFS显著优于单药IO（风险比：1.81，95%置信区间：1.18~2.78）；当肿瘤PD-L1表达水平≥1%时，IC方案的OS与PFS同样更具优势。单药IO的不良事件总发生率低于IC方案，但免疫相关不良事件的发生率更高。

研究结论：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作为一线治疗方案的疗效显著优于单药IO。