目的:本研究的目的是探讨新辅助程序性细胞死亡(或配体)(PD-(L)1)阻断在PD-L1表达阴性的可切除非小细胞肺癌(NSCLC)患者中的临床益处和必要性。
方法:比较无事件生存率(EFS)的随机对照试验(RCT),总生存期(OS),主要病理反应(MPR),根据PD-L1表达分层的可切除NSCLC患者的新辅助化疗免疫疗法(nCIT)和新辅助化疗(nCT)之间的病理完全缓解(pCR)符合纳入研究的条件.使用随机和固定模型,通过比值比(OR)和风险比(HR)以95%置信区间(CI)评估有关病理反应和EFS的数据。
结果:共纳入6个RCTs,涉及3,194例有或没有新辅助免疫治疗的可切除NSCLC患者。与单独的nCT相比,nCIT显着提高了pCR(18.3%与3.0%;或,5.64;95%CI,3.22-9.89;P<0.001),MPR(38.9%与15.5%;或,3.57;95%CI,2.10-6.05;P<0.001),和EFS(HR,0.75;95%CI,0.62-0.90;P=0.002)在PD-L1<1%NSCLC患者中。此外,PD-L1≥1%与较高的pCR率相关(32.8%与18.3%;或,2.28;95%CI,1.40-3.73;P=0.001)和MPR(53.9%vs.38.9%;或1.84;95%CI,1.22-2.79;P=004)和更长的EFS(HR,0.44vs.0.75)在nCIT的设置中,与PD-L1<1%相比。在PD-L1≥1%的NSCLC患者中,nCIT仅改善OS,而在PD-L1<1%的患者中没有改善。
结论:对于PD-L1表达阴性的可切除NSCLC患者,应推荐使用nCIT,因为nCIT显著改善了这些患者的病理反应和EFS。在OS上接受nCIT治疗的PD-L1阴性患者的益处仍有待验证。
OBJECTIVE: The aim of this study was to investigate the clinical benefit and necessity of neoadjuvant programmed cell death (or ligand) (PD-(L)1) blockades in resectable non-small cell lung cancer (NSCLC) patients with negative PD-L1 expression.
METHODS: Randomized control trials (RCTs) that compared event-free survival (EFS), overall survival (OS), major pathological response (MPR), and/or pathological complete response (pCR) between neoadjuvant chemo-immunotherapy (nCIT) and neoadjuvant chemotherapy (nCT) for patients with resectable NSCLC stratified by PD-L1 expression were eligible for inclusion in the study. Data regarding the pathological response and EFS were evaluated by the odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) using random and fixed models.
RESULTS: A total of six RCTs involving 3,194 patients with resectable NSCLC with or without neoadjuvant immunotherapy were included. Compared with nCT alone, nCIT significantly improved pCR (18.3 % vs. 3.0 %; OR, 5.64; 95 % CI, 3.22-9.89; P < 0.001), MPR (38.9 % vs. 15.5 %; OR, 3.57; 95 % CI, 2.10-6.05; P < 0.001), and EFS (HR, 0.75; 95 % CI, 0.62-0.90; P = 0.002) in PD-L1 <1 % NSCLC patients. In addition, PD-L1 ≥1 % was associated with higher rates of pCR (32.8 % vs. 18.3 %; OR, 2.28; 95 % CI, 1.40-3.73; P = 0.001) and MPR (53.9 % vs. 38.9 %; OR, 1.84; 95 % CI, 1.22-2.79; P = 004) and longer EFS (HR, 0.44 vs. 0.75) in the setting of nCIT compared with PD-L1 <1 %. nCIT improved only OS in NSCLC patients with PD-L1 ≥1 % but not in patients with PD-L1 <1 %.
CONCLUSIONS: The use of nCIT should be recommended for resectable NSCLC patients with negative PD-L1 expression, as nCIT significantly improved the pathological response and EFS in these patients. The benefit to PD-L1-negative patients treated with nCIT on OS remains to be validated.