Impact of the timing of immunotherapy administration on overall survival for resectable non-small cell lung cancer (iACORN study): A systematic review and meta-analysis of randomised trials

IF 7.6 1区医学 Q1 ONCOLOGY

European Journal of Cancer Pub Date : 2024-11-09 DOI:10.1016/j.ejca.2024.115118

Akshay J. Patel , Hanan Hemead , Jacie Law , Anuj Wali , Paulo De Sousa , Eric Lim

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引用次数: 0

Abstract

Background

We sought to investigate the relative impact of the timing of the administration of immunotherapy on survival in patients with resectable lung cancer.

Methods

We conducted a systematic review and meta-analysis of randomised controlled trials in this setting. We searched MEDLINE, EMBASE, LILACS and Cochrane Library databases from 1st January 1980 onwards. We excluded case reports; non-randomised studies; studies without an immunotherapy arm and if there was incomplete reporting on outcome data including conference abstracts. A standardised, pre-piloted form was used to extract data from the included studies for the assessment of study quality and for evidence synthesis. The primary outcome measure was overall survival which was assessed using random-effects meta-analyses (DerSimonian and Laird). The study was registered with PROSPERO (CRD42023407825).

Findings

We screened 865 studies and assessed 58 full text articles after removing non-human, non-surgical studies. These studies collectively enrolled 4982 participants and 4425 were included in the respective analyses. Hazard ratios (HRs) for death by timing of administration of immunotherapy, i.e., Neoadjuvant (pre-operative), peri-operative and post-operative were 0.57 (95 % CI 0.302–1.08), 0.67 (95 % CI 0.39–1.13) and 0.94 (95 % CI 0.29–3.06) respectively. The timing of administration accounted for 100 % of the difference in true effect size (test of moderators (Q_M p = 0.127), residual I² 0 %, p = 0.561). OR for adverse events was higher in the neoadjuvant setting compared to the peri-operative setting; 1.49 (0.64–3.47) and 1.34 (1.08–1.66) respectively. Bias assessment found the majority of studies to be low risk with respect to random sequencing, incomplete outcomes, and selective reporting.

Interpretation

In resectable non-small cell lung cancer, administration of adjuvant chemo-immunotherapy regimens in clinical trials did not lead to statistically significant survival benefits. Overall survival outcomes of neoadjuvant and peri-operative chemo-immunotherapy were comparable, but given the shorter duration and lower costs, neoadjuvant chemo-immunotherapy can be considered the current multimodality combination of choice.

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免疫疗法给药时机对可切除非小细胞肺癌总生存期的影响（iACORN 研究）：随机试验的系统回顾和荟萃分析。

背景我们试图研究免疫疗法的施用时机对可切除肺癌患者生存期的相对影响：我们对这种情况下的随机对照试验进行了系统回顾和荟萃分析。我们检索了自 1980 年 1 月 1 日起的 MEDLINE、EMBASE、LILACS 和 Cochrane Library 数据库。我们排除了病例报告、非随机研究、没有免疫疗法部分的研究，以及包括会议摘要在内的结果数据报告不完整的研究。我们采用了预先试行的标准化表格，从纳入的研究中提取数据，用于评估研究质量和证据综合。主要结果指标是总生存率，采用随机效应荟萃分析法（DerSimonian 和 Laird）进行评估。该研究已在 PROSPERO 注册（CRD42023407825）：我们筛选了 865 项研究，并在删除非人类、非手术研究后评估了 58 篇全文文章。这些研究共招募了 4982 名参与者，其中 4425 人被纳入相关分析。根据免疫疗法的施用时机，即新辅助治疗（术前）、围手术期和术后，死亡的危险比（HRs）分别为 0.57（95 % CI 0.302-1.08）、0.67（95 % CI 0.39-1.13）和 0.94（95 % CI 0.29-3.06）。给药时间占真实效应大小差异的 100%（调节因子检验 (QM p = 0.127)，残差 I2 0 %，p = 0.561）。与围手术期相比，新辅助治疗的不良反应发生率更高，分别为1.49（0.64-3.47）和1.34（1.08-1.66）。偏倚评估发现，大多数研究在随机排序、结果不完整和选择性报告方面风险较低：对于可切除的非小细胞肺癌，在临床试验中采用辅助化疗-免疫治疗方案并不能带来统计学意义上的生存获益。新辅助化疗免疫疗法和围手术期化疗免疫疗法的总生存率不相上下，但鉴于新辅助化疗免疫疗法疗程短、费用低，因此可将其视为目前多模式联合疗法的首选。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Cancer 医学-肿瘤学

CiteScore

11.50

自引率

4.80%

发文量

953

审稿时长

23 days

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