上皮癌患者中PD-1/PD-L1阻断剂的疗效及潜在预测因素：一项系统评价和荟萃分析
The efficacy and potential predictive factors of PD-1/PD-L1 blockades in epithelial carcinoma patients: a systematic review and meta analysis.
作者信息
Yang Yufan, Pang ZhaoFei, Ding Nan, Dong Wei, Ma Wei, Li Yun, Du Jiajun, Liu Qi
机构信息
Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, Peoples's Republic of China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, Shandong, Peoples's Republic of China.
出版信息
Oncotarget. 2016 Nov 8;7(45):74350-74361. doi: 10.18632/oncotarget.11291.
BACKGROUND
This systematic analysis aims to assess the efficacy of PD-1/PD-L1 blockades compared with non-PD-1/PD-L1 therapy and investigate the potential predictive factors in epithelial carcinoma patients.
RESULTS
A total of 11 trials with 6716 patients of melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) were included. The pooled HRs (95%CI) were 0.67 (0.62, 0.73), p < 0.001 for OS and 0.66 (0.57, 0.76), p < 0.001 for PFS. In subgroup analyses, HRs were 0.58 (0.50, 0.66), p < 0.001 in PD-L1 ≥ 1% group, 0.75 (0.63, 0.89), p = 0.001 in PD-L1 < 1% group for OS and 0.59 (0.48, 0.72), p < 0.001 in PD-L1 ≥ 1% group, 0.80 (0.59, 1.07), p = 0.136 in PD-L1 < 1% group for PFS. The p values of pooled HRs for OS in different age, sex and ECOG score groups were less than 0.001. In NSCLC patients, aggregated HRs for OS were 1.40 (0.92, 2.12), p = 0.114 in EGFR mutant group and 0.88 (0.59, 1.32), p = 0.536 in never smokers.
METHODS
A systematic search from January 2010 to April 2016 was conducted for eligible clinical trials. Based on the data of hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS), we assessed the pooled HRs and proposed the subgroup analyses.
CONCLUSIONS
PD-1/PD-L1 blockades prolonged OS and PFS in epithelial carcinoma patients. PD-L1 expression was a predictive factor for PFS but not predictive for OS. Age, sex and ECOG score were excluded to predict any of the efficacy endpoints. Smoking history and EGFR wild type were associated with extended OS in NSCLC patients.
背景
本系统分析旨在评估与非PD-1/PD-L1疗法相比，PD-1/PD-L1阻断剂的疗效，并研究上皮癌患者的潜在预测因素。
结果
共纳入11项试验，涉及6716例黑色素瘤、非小细胞肺癌（NSCLC）和肾细胞癌（RCC）患者。总生存（OS）的合并风险比（HRs）（95%置信区间）为0.67（0.62，0.73），p<0.001；无进展生存（PFS）的合并HRs为0.66（0.57，0.76），p<0.001。在亚组分析中，OS方面，PD-L1≥1%组的HRs为0.58（0.50，0.66），p<0.001，PD-L1<1%组的HRs为0.75（0.63，0.89），p=0.001；PFS方面，PD-L1≥1%组的HRs为0.59（0.48，0.72），p<0.001，PD-L1<1%组的HRs为0.80（0.59，1.07），p=0.136。不同年龄、性别和ECOG评分组OS的合并HRs的p值均小于0.001。在NSCLC患者中，表皮生长因子受体（EGFR）突变组OS的汇总HRs为1.40（0.92，2.12），p=0.114，从不吸烟者的HRs为0.88（0.59，1.32），p=0.536。
方法
对2010年1月至2016年4月符合条件的临床试验进行系统检索。基于总生存（OS）和无进展生存（PFS）的风险比（HRs）及95%置信区间（CIs）数据，我们评估了合并HRs并进行亚组分析。
结论
PD-1/PD-L1阻断剂可延长上皮癌患者的OS和PFS。PD-L1表达是PFS的预测因素，但不是OS的预测因素。年龄、性别和ECOG评分均不能预测任何疗效终点。吸烟史和EGFR野生型与NSCLC患者OS延长有关。
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