Peng Siyu, Ying Ariel Fangting, Tai Bee Choo, Soo Ross Andrew
Department of Medicine, National University Health System, Singapore, Singapore.
Health Services and System Research, Duke-NUS Medical School, Singapore, Singapore.
Transl Lung Cancer Res. 2020 Aug;9(4):1124-1137. doi: 10.21037/tlcr-20-246.
We conducted a meta-analysis to assess the efficacy of immune checkpoint inhibitors (ICIs) (PD-1/L1 and CTLA-4 inhibitors) in first and subsequent lines in East Asians and non-East Asians.
We searched PubMed-MEDLINE, Embase and Scopus, from inception to 20 Sep 2019, and reviewed major conferences' abstracts, for randomised controlled trials of ICI in advanced-stage NSCLC (Stage IIIB or IV) without EGFR mutation that reported hazard ratios (HRs) stratified by geographical region including the region "Asia" or "East Asia". The primary outcome measures were overall survival (OS) and progression-free survival (PFS). The pooled HR and its 95% confidence interval (CI) for OS and PFS in East Asians and non-East Asians were calculated using a random effect model and the difference compared using an interaction test.
A total of 5,465 patients from 7 randomised controlled trials involving CTLA-4 and/or PD-1/L1 inhibitors were included, with 1,740 (32%) East Asians and 3,725 (68%) non-East Asians. ICI was associated with an improvement in OS and PFS for both East Asian (OS HR, 0.74; 95% CI, 0.65-0.85; PFS HR, 0.56; 95% CI, 0.40-0.79) and non-East Asian patients (OS HR, 0.78; 95% CI, 0.72-0.85; PFS HR, 0.69; 95% CI, 0.56-0.85), with no significant difference between the two groups (P=0.55 for OS; P=0.33 for PFS). Subgroup analyses showed a statistically significant superior PFS (but not OS) for East Asians than non-East Asians in trials that used immune checkpoint inhibitor in the first-line treatment (P=0.02). No significant regional difference was found in further subgroups of pure ICI and combination of ICI with chemotherapy.
There is no significant difference in response to ICI between East Asians and non-East Asians with advanced stage NSCLC, and the statistically significant subgroup difference in PFS in the first line use of ICI may not be clinically significant.
我们进行了一项荟萃分析,以评估免疫检查点抑制剂(ICIs)(PD-1/L1和CTLA-4抑制剂)在东亚人和非东亚人一线及后续治疗中的疗效。
我们检索了PubMed-MEDLINE、Embase和Scopus数据库,检索时间从建库至2019年9月20日,并查阅了主要会议的摘要,以寻找关于ICI用于晚期非小细胞肺癌(IIIB期或IV期)且无EGFR突变的随机对照试验,这些试验报告了按地理区域分层的风险比(HRs),地理区域包括“亚洲”或“东亚”地区。主要结局指标为总生存期(OS)和无进展生存期(PFS)。采用随机效应模型计算东亚人和非东亚人OS和PFS的合并HR及其95%置信区间(CI),并使用交互检验比较两者差异。
共纳入7项涉及CTLA-4和/或PD-1/L1抑制剂的随机对照试验中的5465例患者,其中东亚人1740例(32%),非东亚人3725例(68%)。ICI使东亚患者(OS HR,0.74;95%CI,0.65-0.85;PFS HR,0.56;95%CI,0.40-0.79)和非东亚患者(OS HR,0.78;95%CI,0.72-0.85;PFS HR,0.69;95%CI,0.56-0.85)的OS和PFS均得到改善,两组之间无显著差异(OS的P=0.55;PFS的P=0.33)。亚组分析显示,在一线治疗中使用免疫检查点抑制剂的试验中,东亚人的PFS(而非OS)在统计学上显著优于非东亚人(P=0.02)。在单纯ICI以及ICI与化疗联合的进一步亚组中未发现显著的区域差异。
晚期非小细胞肺癌的东亚人和非东亚人对ICI的反应无显著差异,ICI一线使用时PFS在统计学上显著的亚组差异可能无临床意义。