Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China.
Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
Front Immunol. 2021 Jun 2;12:666909. doi: 10.3389/fimmu.2021.666909. eCollection 2021.
Atezolizumab plus chemotherapy has been recommended as a first-line treatment option for patients with advanced non-small cell lung carcinoma (NSCLC) irrespective of programmed cell death-ligand 1 (PD-L1) expression. Currently, little is known about the efficacy and treatment-related adverse effects (TRAEs) of subtracting chemotherapy from the combination for patients with high PD-L1 expression. Thus, we performed an indirect comparison between atezolizumab plus chemotherapy and atezolizumab alone.
A total of five eligible randomized controlled trials (RCTs) were identified from PubMed, EMBASE, and Cochrane Central controlled trial registries, using keywords including atezolizumab, PD-1, PD-L1, NSCLC, and RCT. The clinical outcomes of objective response rate (ORR), progression-free survival (PFS), OS, and TRAEs were extracted and evaluated. Using indirect analysis, the efficacy and TRAEs were compared between arm A (atezolizumab plus chemotherapy) and arm C (atezolizumab), linked by arm B (chemotherapy).
Direct comparison revealed that both atezolizumab plus chemotherapy (HR 0.65, = 0.003) and atezolizumab alone (HR 0.59, = 0.010) significantly improved OS compared with chemotherapy. More importantly, the indirect comparison showed that atezolizumab plus chemotherapy was not superior to atezolizumab regarding OS (RR 1.10, =0.695) and ORR (RR 1.11, = 0.645). However, patients who received atezolizumab combined with chemotherapy experienced more ≥ grade 3 TRAEs (RR 4.23, <0.001) and TRAEs leading to drug discontinuation (RR 3.60, <0.001) than those treated with atezolizumab monotherapy.
Atezolizumab monotherapy might be a better treatment option for patients with advanced NSCLC and high PD-L1 expression than atezolizumab plus chemotherapy.
阿替利珠单抗联合化疗已被推荐为晚期非小细胞肺癌（NSCLC）患者的一线治疗选择，无论其程序性死亡配体 1（PD-L1）表达如何。目前，对于高 PD-L1 表达的患者，从联合治疗中减去化疗对疗效和治疗相关不良事件（TRAEs）的影响知之甚少。因此，我们对阿替利珠单抗联合化疗与阿替利珠单抗单药治疗进行了间接比较。
通过关键词包括阿替利珠单抗、PD-1、PD-L1、NSCLC 和 RCT，从 PubMed、EMBASE 和 Cochrane 中心对照试验注册中心共确定了五项符合条件的随机对照试验（RCT）。提取并评估了客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和 TRAEs 的临床结局。通过间接分析，以化疗为中介，将阿替利珠单抗联合化疗组（A 组）与阿替利珠单抗组（C 组）进行比较。
直接比较显示，阿替利珠单抗联合化疗（HR 0.65， = 0.003）和阿替利珠单抗单药治疗（HR 0.59， = 0.010）均显著改善了 OS。更重要的是，间接比较显示，阿替利珠单抗联合化疗在 OS（RR 1.10， = 0.695）和 ORR（RR 1.11， = 0.645）方面并不优于阿替利珠单抗单药治疗。然而，接受阿替利珠单抗联合化疗的患者发生≥3 级 TRAEs（RR 4.23， ＜0.001）和因 TRAEs 而停药（RR 3.60， ＜0.001）的比例高于接受阿替利珠单抗单药治疗的患者。
对于高 PD-L1 表达的晚期 NSCLC 患者，阿替利珠单抗单药治疗可能是优于阿替利珠单抗联合化疗的治疗选择。
