Patel Akshay J, Hemead Hanan, Law Jacie, Wali Anuj, De Sousa Paulo, Lim Eric
Department of Thoracic Surgery, University Hospitals Birmingham NHS Foundation Trust, UK; Institute of Immunology and Immunotherapy, University of Birmingham, UK.
Department of Thoracic Surgery, University Hospitals Birmingham NHS Foundation Trust, UK; Alexandria Faculty of Medicine, Alexandria University, Egypt.
Eur J Cancer. 2025 Jan;214:115118. doi: 10.1016/j.ejca.2024.115118. Epub 2024 Nov 9.
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 p = 0.127), residual I 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.
背景：我们试图研究免疫疗法给药时机对可切除肺癌患者生存率的相对影响。 方法：我们对该领域的随机对照试验进行了系统评价和荟萃分析。我们检索了自1980年1月1日起的MEDLINE、EMBASE、LILACS和Cochrane图书馆数据库。我们排除了病例报告；非随机研究；没有免疫治疗组的研究，以及如果结局数据报告不完整（包括会议摘要）的研究。使用标准化的、预先试点的表格从纳入研究中提取数据，以评估研究质量和进行证据综合。主要结局指标是总生存期，使用随机效应荟萃分析（DerSimonian和Laird方法）进行评估。该研究已在PROSPERO注册（CRD42023407825）。 结果：我们筛选了865项研究，在排除非人类、非手术研究后评估了58篇全文文章。这些研究共纳入4982名参与者，4425名被纳入各自的分析。根据免疫疗法给药时机（即新辅助（术前）、围手术期和术后）的死亡风险比（HR）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）。给药时机占真实效应大小差异的100%（调节因素检验（Q p = 0.127），残差I² 0%，p = 0.561）。新辅助治疗组不良事件的比值比高于围手术期治疗组；分别为1.49（0.64 - 3.47）和1.34（1.08 - 1.66）。偏倚评估发现，大多数研究在随机序列、不完整结局和选择性报告方面风险较低。 解读：在可切除的非小细胞肺癌中，临床试验中给予辅助化疗免疫治疗方案未产生统计学上显著的生存获益。新辅助和围手术期化疗免疫治疗的总生存结局相当，但考虑到疗程较短和成本较低，新辅助化疗免疫治疗可被视为当前的多模式联合选择。
Cochrane Database Syst Rev. 2018-2-6
Cochrane Database Syst Rev. 2017-12-16
Cochrane Database Syst Rev. 2023-1-17
Cochrane Database Syst Rev. 2015-1-1
Cochrane Database Syst Rev. 2015-1-14
Cochrane Database Syst Rev. 2015-4-7
Cochrane Database Syst Rev. 2015-3-2
Cochrane Database Syst Rev. 2023-8-31
Zotero 插件