VEGF抑制剂联合酪氨酸激酶抑制剂一线治疗EGFR突变晚期非小细胞肺癌的疗效和安全性

Efficacy and safety of vascular endothelial growth factor(VEGF)inhibitors combined with tyrosine kinase inhibitors in the first-line treatment of epidermal growth factor receptor(EGFR)-mutant advanced non-small cell lung cancer

目的:探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)抑制剂联合酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)一线治疗表皮生长因子受体(epidermal growth factor receptor,EGFR)突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效和安全性。方法:比较抗VEGF药物联合EGFR-TKI与单用EGFR-TKI作为晚期非小细胞肺癌EGFR突变型患者的一线治疗疗效及毒副反应。结果:此研究共纳入5项随机对照试验(randomized controlled trial,RCT),共有1230名非小细胞肺癌患者,亚洲人占1042人。抗VEGF药物联合EGFR-TKI较单用EGFR-TKI,其主要研究终点PFS明显延长(HR=0.59,95%CI:0.51~0.69),无论在EGFR 19外显子缺失突变(HR=0.59,95%CI:0.50~0.70)或者21外显子L858R突变(HR=0.58,95%CI:0.48~0.72),其PFS都取得临床获益,而对于次要研究指标OS无统计学差异(HR=0.93,95%CI:0.74~1.17)。联合组Ⅲ级以上的高血压、蛋白尿及皮疹发生率显著增加,以蛋白尿发生率增高更为明显。结论:对于晚期非小细胞肺癌EGFR突变阳性患者,EGFR-TKI联合抗VEGF较单独使用EGFR-TKI治疗,PFS明显获益,但却未能转化成长期生存获益。

Objective:To investigate the efficacy and safety of vascular endothelial growth factor(VEGF)inhibitors combined with tyrosine kinase inhibitors(TKI)in the first-line treatment of epidermal growth factor receptor(EGFR)-mutant advanced non-small cell lung cancer(NSCLC).Methods:The efficacy and side effects of anti-VEGF drugs combined with EGFR-TKI and EGFR-TKI alone as the first-line treatment for patients with EGFR-mutant advanced NSCLC were compared.Results:This study included 5 randomized controlled trials(RCTs)involving a total of 1230 patients with NSCLC,1042(85%)of whom were Asian.PFS was chosen as the primary end point,with a secondary endpoint of OS.Our results showed that the combination of EGFR-TKI with anti-VEGF drugs significantly improved PFS(HR=0.59,95%CI:0.51~0.69)compared with EGFR-TKI alone for patients with EGFR mutations,including the exon 19 deletion(HR=0.59,95%CI:0.50~0.70)and exon 21 L858R mutation(HR=0.58,95%CI:0.48~0.72).However,it did not improve OS(HR=0.93,95%CI:0.74~1.17).The more incidence of gradeⅢhypertension,proteinuria and rash were observed in the combination group,and the incidence of proteinuria was higher.Conclusion:The combination of EGFR-TKI with anti-VEGF drugs resulted in a significant benefit in PFS compared with EGFR-TKI alone,but it failed to provide any long-term survival benefits in patients with EGFR mutation-positive advanced NSCLC.