PD-1/PD-L1抑制剂对比化疗一线治疗晚期非小细胞肺癌的Meta分析

目的系统评价PD-1/PD-L1抑制剂对比化疗一线治疗晚期非小细胞肺癌的疗效及安全性。方法通过Web of science等国内外数据库,ASCO会议摘要及杂志筛选文献,进行Meta分析。结果纳入7项RCT研究,4 101例患者,荟萃分析显示抑制剂联合化疗对比化疗可显著延长患者的PFS(HR=0.59, 95%CI:0.50～0.70,P<0.00001)、OS(HR=0.65, 95%CI:0.46～0.92,P=0.02)及ORR(RR=1.72, 95%CI:1.13～2.62,P=0.01)。亚组分析显示,抑制剂联合化疗可显著延长PFS及OS,且PD-L1表达程度越高,疗效获益越显著。而单药抑制剂对比化疗在延长晚期NSCLC患者的PFS(HR=0.87, 95%CI:0.57～1.31, P=0.50)、OS(HR=0.82, 95%CI:0.65～1.03, P=0.09)及提高ORR(RR=1.12, 95%CI:0.55～2.28, P=0.76)方面两组差异无统计学意义。与化疗相比,单药抑制剂一线治疗PD-L1高表达的晚期NSCLC患者可显著延长OS,但在延长PFS方面未见明显优势。与化疗组相比,抑制剂联合化疗组3～4级不良反应发生率无明显改善(HR=1.09,95%CI:0.99～1.20,P=0.09),而单药PD-1/PD-L1抑制剂组3～4级不良反应发生率低(RR=0.43,95%CI:0.36～0.52, P<0.00001)。结论 PD-1/PD-L1抑制剂联合化疗一线治疗晚期NSCLC患者疗效优于化疗方案;PD-L1高表达者单药PD-1/PD-L1抑制剂可作为一线治疗的优先选择,且具有良好的安全性。

Efficacy and Safety of PD-1/PD-L1 Inhibitor Versus Chemotherapy in First-line Treatment of Advanced Non-small Cell Lung Cancer: A Meta-analysis

Objective To review the effectiveness and safety of PD-1/PD-L1 inhibitor versus chemotherapy in the first-line treatment of advanced non-small cell lung cancer. Methods Relevant literatures were searched through Web of Science database, ASCO meeting abstract, journals, etc. for meta-analysis. Results Totally 7 RCTs including 4101 patients were analyzed. The meta-analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitor combined with chemotherapy significantly prolonged PFS (HR=0.59, 95%CI: 0.59-0.70, P<0.00001), OS (HR=0.65, 95%CI: 0.65-0.92, P=0.02) and ORR (RR=1.72, 95%CI: 1.13-2.62, P=0.01). Subgroup analysis showed PD-1/PD-L1 inhibitor combined with chemotherapy could significantly prolong PFS and OS, compared with chemotherapy. The higher PD-L1 expression was, the more significant the curative effect was. There was no statistical significance in prolonging PFS (HR=0.87, 95%CI: 0.57-1.31, P=0.50), OS (HR=0.82, 95%CI: 0.65-1.03, P=0.09) or increasing ORR (RR=1.12, 95%CI: 0.55-2.28, P=0.76) between single-agent PD-1/PD-L1 inhibitor and chemotherapy. Compared with chemotherapy, single-agent PD-1/PD-L1 inhibitor in the first-line treatment could significantly prolong the OS of advanced NSCLC patients with high PD-L1 expression. Grade 3-4 treatment-related adverse effect was not statistically significant different between PD-1/PD-L1 inhibitor combined with chemotherapy group and chemotherapy group (HR=1.09, 95%CI: 0.99-1.20, P=0.09), while that in single-agent PD-1/PD-L1 inhibitor group was lower (RR=0.43, 95%CI: 0.36-0.52, P<0.00001). Conclusion Compared with chemotherapy, PD-1/PD-L1 inhibitor combined with chemotherapy in the first-line treatment on advanced NSCLC patients is more effective; single-agent PD-1/PD-L1 inhibitor should be used as the first-line treatment preferentially on advanced NSCLC patient with high PD-L1 expression.