Wenfan Fu, Manman Xu, Xingyuan Shi, Zeyong Jiang, Jian Zhao, Lu Dai
Department of Chest Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, Guangdong, China.
Southern Medical University, Guangzhou, Guangdong, China.
Ther Adv Chronic Dis. 2023 Oct 11;14:20406223231189224. doi: 10.1177/20406223231189224. eCollection 2023.
BACKGROUND: Numerous first-line immune checkpoint inhibitors (ICI) were developed for patients with advanced non-small cell lung cancer (NSCLC) lacking driver gene mutations. However, this group consists of a heterogeneous patient population, for whom the optimal therapeutic choice is yet to be confirmed. OBJECTIVE: To identify the best first-line immunotherapy regimen for overall advanced NSCLC patients and different subgroups. DESIGN: Systematic review and Bayesian network meta-analysis (NMA). METHODS: We searched several databases to retrieve relevant literature. We performed Bayesian NMA for the overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (tr-AEs) with a grade equal or more than 3 (grade ⩾ 3 tr-AEs). Subgroup analysis was conducted according to programed death ligand 1 (PD-L1) levels, histologic type, central nervous system (CNS) metastases and tobacco use history. RESULTS: For the PD-L1 non-selective patients, sintilimab plus chemotherapy (sinti-chemo) provided the best OS [hazard ratio (HR) = 0.59, 95% confidence interval (CI):0.42-0.83]. Nivolumab plus bevacizumab plus chemotherapy (nivo-bev-chemo) was comparable to atezolizumab plus bevacizumab plus chemotherapy (atezo-bev-chemo) in prolonging PFS (HR = 0.99, 95% CI: 0.51-1.91). Atezo-bev-chemo remarkably elevated the ORR than chemotherapy (OR = 3.13, 95% CI: 1.51-6.59). Subgroup analysis showed pembrolizumab plus chemotherapy (pembro-chemo) ranked first in OS in subgroups of PD-L1 < 1%, non-squamous, no CNS metastases, with or without smoking history, and ranked second in OS in subgroups of PD-L1 ⩾ 1% and PD-L1 1-49%. Cemiplimab and sugemalimab plus chemotherapy ranked first in OS and PFS for squamous subgroup, respectively. For patients with CNS metastases, nivolumab plus ipilimumab plus chemotherapy (nivo-ipili-chemo) and camrelizumab plus chemotherapy provided the best OS and PFS, respectively. CONCLUSIONS: Sinti-chemo and nivo-bev-chemo were two effective first-line regimens ranked first in OS and PFS for overall patients, respectively. Pembro-chemo was favorable for patients in subgroups of PD-L1 < 1%, PD-L1 ⩾ 1%, PD-L1 1-49%, non-squamous, no CNS metastases, with or without smoking history. Addition of bevacizumab consistently provided with favorable PFS results in patients of all PD-L1 levels. Cemiplimab was the best option in squamous subgroup and nivo-ipili-chemo in CNS metastases subgroup due to their advantages in OS.
背景：众多一线免疫检查点抑制剂（ICI）已被开发用于缺乏驱动基因突变的晚期非小细胞肺癌（NSCLC）患者。然而，这一患者群体具有异质性，其最佳治疗选择尚未得到证实。 目的：确定适用于所有晚期NSCLC患者及不同亚组的最佳一线免疫治疗方案。 设计：系统评价和贝叶斯网络荟萃分析（NMA）。 方法：我们检索了多个数据库以获取相关文献。我们对总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）以及3级及以上的治疗相关不良事件（tr-AEs）进行了贝叶斯NMA。根据程序性死亡配体1（PD-L1）水平、组织学类型、中枢神经系统（CNS）转移情况和吸烟史进行亚组分析。 结果：对于PD-L1非选择性患者，信迪利单抗联合化疗（信迪利单抗-化疗）提供了最佳的总生存期[风险比（HR）=0.59，95%置信区间（CI）：0.42-0.83]。纳武利尤单抗联合贝伐珠单抗联合化疗（纳武利尤单抗-贝伐珠单抗-化疗）在延长无进展生存期方面与阿替利珠单抗联合贝伐珠单抗联合化疗（阿替利珠单抗-贝伐珠单抗-化疗）相当（HR=0.99，95%CI：0.51-1.91）。阿替利珠单抗-贝伐珠单抗-化疗的客观缓解率显著高于化疗（OR=3.13，95%CI：1.51-6.59）。亚组分析显示，帕博利珠单抗联合化疗（帕博利珠单抗-化疗）在PD-L1＜1%、非鳞状、无CNS转移、有或无吸烟史的亚组中总生存期排名第一，在PD-L1≥1%和PD-L1 1-49%的亚组中总生存期排名第二。西米普利单抗和苏金单抗联合化疗分别在鳞状亚组的总生存期和无进展生存期方面排名第一。对于有CNS转移的患者，纳武利尤单抗联合伊匹木单抗联合化疗（纳武利尤单抗-伊匹木单抗-化疗）和卡瑞利珠单抗联合化疗分别提供了最佳的总生存期和无进展生存期。 结论：信迪利单抗-化疗和纳武利尤单抗-贝伐珠单抗-化疗分别是总体患者总生存期和无进展生存期排名第一的两种有效一线方案。帕博利珠单抗-化疗对PD-L1＜1%、PD-L1≥1%、PD-L1 1-49%、非鳞状、无CNS转移、有或无吸烟史的亚组患者有利。在所有PD-L1水平的患者中，添加贝伐珠单抗始终能带来良好的无进展生存期结果。由于其在总生存期方面的优势，西米普利单抗是鳞状亚组的最佳选择，纳武利尤单抗-伊匹木单抗-化疗是CNS转移亚组的最佳选择。
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