He Zhe, Zhu Qihang, Xia Xin, Wu Junhan, Xiao Haiping, Qiao Guibin, Tang Yong
Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
J Thorac Dis. 2024 Oct 31;16(10):6699-6712. doi: 10.21037/jtd-24-287. Epub 2024 Oct 11.
A series of randomized controlled trials (RCTs) have demonstrated the promising prospect of immunotherapy in operable non-small cell lung cancer (NSCLC) and further changed the clinical practice. However, current studies still yet to answer which immunotherapy mode is the optimal strategy, and there is currently a lack of direct comparison between neoadjuvant immunochemotherapy and perioperative immunotherapy ("sandwich mode", including neoadjuvant immunochemotherapy and adjuvant immunotherapy). Thus, we conducted a network meta-analysis (NMA) to evaluate the efficacy between neoadjuvant immunochemotherapy and perioperative immunotherapy.
We performed a Bayesian NMA (PROSPERO registration number: CRD42024495955) by retrieving relevant eligible studies from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and major international conferences until December 31, 2023. Phase II or III RCTs that evaluated the efficacy of different strategies of immunotherapy in operable NSCLC, including neoadjuvant immunochemotherapy and perioperative immunotherapy ("sandwich mode"), were retrieved for analysis. The patients were grouped into neoadjuvant chemotherapy alone (arm A), neoadjuvant immunotherapy plus chemotherapy (arm B); neoadjuvant immunotherapy plus chemotherapy followed by surgery and adjuvant immunotherapy (arm C), respectively. The endpoint was event-free survival (EFS) in different subgroups.
Seven studies of 2,934 patients were selected for this NMA finally. Compared with neoadjuvant chemotherapy, both neoadjuvant immunochemotherapy [hazard ratio (HR) 0.61, 95% confidence interval (CI): 0.36-0.98] and perioperative immunotherapy (HR 0.56, 95% CI: 0.42-0.71) significantly improved the EFS in intention-to-treat population, but there was no statistical difference between these two treatments (HR 1.1, 95% CI: 0.62-1.9). There was no statistical difference between perioperative immunotherapy and neoadjuvant immunochemotherapy in all subgroup analysis of EFS. However, in patients with non-squamous disease, programmed cell death-ligand 1 (PD-L1) expression more than 50%, or stage III disease, both neoadjuvant immunotherapy [(HR 0.50, 95% CI: 0.26-0.97), (HR 0.24, 95% CI: 0.061-0.96), (HR 0.50, 95% CI: 0.39-0.63)] and perioperative immunotherapy [(HR 0.64, 95% CI: 0.46-0.87), (HR 0.40, 95% CI: 0.21-0.71), (HR 0.54, 95% CI: 0.34-0.85)] improved EFS significantly compared with neoadjuvant chemotherapy.
Both neoadjuvant immunochemotherapy and perioperative immunotherapy significantly increased EFS compared with neoadjuvant chemotherapy. There is no evidence that perioperative immunotherapy is better than neoadjuvant immunochemotherapy in EFS. Patients with non-squamous disease, PD-L1 expression more than 50%, or stage III disease can try the neoadjuvant immunochemotherapy mode.
一系列随机对照试验（RCT）已证明免疫疗法在可手术的非小细胞肺癌（NSCLC）中具有广阔前景，并进一步改变了临床实践。然而，目前的研究仍未回答哪种免疫治疗模式是最佳策略，且目前新辅助免疫化疗与围手术期免疫治疗（“三明治模式”，包括新辅助免疫化疗和辅助免疫治疗）之间缺乏直接比较。因此，我们进行了一项网络荟萃分析（NMA）以评估新辅助免疫化疗与围手术期免疫治疗之间的疗效。
我们通过从PubMed、EMBASE、Cochrane图书馆、ClinicalTrials.gov以及主要国际会议中检索相关合格研究，直至2023年12月31日，进行了一项贝叶斯NMA（PROSPERO注册号：CRD42024495955）。检索评估免疫疗法不同策略在可手术NSCLC中的疗效的II期或III期RCT，包括新辅助免疫化疗和围手术期免疫治疗（“三明治模式”），进行分析。患者分别分为单纯新辅助化疗（A组）、新辅助免疫治疗加化疗（B组）；新辅助免疫治疗加化疗后手术及辅助免疫治疗（C组）。终点是不同亚组的无事件生存期（EFS）。
最终选择了7项研究共2934例患者进行该NMA。与新辅助化疗相比，新辅助免疫化疗[风险比（HR）0.61，95%置信区间（CI）：0.36 - 0.98]和围手术期免疫治疗（HR 0.56，95% CI：0.42 - 0.71）在意向性治疗人群中均显著改善了EFS，但这两种治疗之间无统计学差异（HR 1.1，95% CI：0.62 - 1.9）。在EFS的所有亚组分析中，围手术期免疫治疗与新辅助免疫化疗之间无统计学差异。然而，在非鳞状疾病、程序性细胞死亡配体1（PD - L1）表达超过50%或III期疾病的患者中，新辅助免疫治疗[（HR 0.50，95% CI：0.26 - 0.97），（HR 0.24，95% CI：0.061 - 0.96），（HR 0.50，95% CI：0.39 - 0.63）]和围手术期免疫治疗[（HR 0.64，95% CI：0.46 - 0.87），（HR 0.40，95% CI：0.21 - 0.71），（HR 0.54，95% CI：0.34 - 0.85）]与新辅助化疗相比均显著改善了EFS。
与新辅助化疗相比，新辅助免疫化疗和围手术期免疫治疗均显著提高了EFS。没有证据表明围手术期免疫治疗在EFS方面优于新辅助免疫化疗。非鳞状疾病、PD - L1表达超过50%或III期疾病的患者可尝试新辅助免疫化疗模式。
