贝伐珠单抗联合EGFR-TKI治疗EGFR外显子19或21突变晚期非小细胞肺癌的疗效差异

Clinical efficacy of bevacizumab combined with EGFR-TKI in treatment of advanced non-small cell lung cancer with EGFR exon 19 or 21 mutation

目的观察贝伐珠单抗联合表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)治疗EGFR外显子19或21突变晚期非小细胞肺癌(NSCLC)患者的疗效差异。方法选择100例EGFR突变阳性的晚期NSCLC患者,其中EGFR外显子19突变50例,外显子21突变50例,将患者随机分为2组,分别使用方案A或B,方案A为贝伐珠单抗联合吉非替尼至进展,方案B为使用吉非替尼至进展。比较2组患者不良反应的发生率和客观缓解率(ORR)、肿瘤无进展生存期(PFS)、总体生存期(OS)。结果外显子19突变患者使用方案A者的ORR为92%,高于方案B者的68%(P<0.05);外显子21突变患者使用方案A者的ORR为88%,亦高于方案B者的60%(P<0.05)。外显子19突变患者使用方案A者的中位PFS为12.5个月,高于使用方案B者的9.0个月(P<0.05);外显子21突变患者使用方案A者的中位PFS为8.9个月,亦高于使用方案B者的7.0个月(P<0.01)。外显子19突变患者使用方案A者和B者的中位OS间比较差异无统计学意义(P>0.05);外显子21突变患者使用方案A者的中位OS(26.7个月)长于方案B者的23.8个月(P<0.01)。外显子19和外显子21突变患者使用方案A者的高血压和蛋白尿发生率高于方案B者(P均<0.05),但患者均可耐受。讨论贝伐珠单抗联合EGFR-TKI在EGFR突变阳性的晚期NSCLC一线治疗中可以作为新的选择方案,尤其应用于外显子21突变患者中可比单纯EGFR-TKI延长PFS和OS。

Objective To compare the clinical efficacy of epiderm al growth factor receptor-tyrosinekinases inhibitor (E G FR -T K I) alone and bevacizumab in com bination with EGFR-TKI in the treatm ent of advancednon-sm all cell lung cancer (N SCLC) with EG FR exon 19 or 21 mutation. Methods In total, 100 advancedNSCLC patients with EG FR m utation, 50 with EG FR exon 19 mutation and 50 with EGFR exon 21 m utation,were randomly divided into two groups. In group A , patients were treated with bevacizumab in com binationwith gefitinib until disease progression and those in group B were given with gefitinib alone until diseaseprogression. The incidence of adverse responses, objective rem ission rate ( O R R ) ,progression-free survival(P F S ) and overall survival (O S ) were statistically compared between two groups. Results For NSCLC patientswith exon 19 m utation, the ORR in group A was 92% , significantly higher com pared with 68% in groupB ( P < 0. 05 ) . For their counterparts with exon 21 m utation, the ORR in group A was 88% , considerablyhigher than 60% in group B ( P < 0 . 0 5 ). For patients with exon 19 m utation, the m edian PFS in group A was12. 5 m onths, significantly longer com pared with 9. 0 months in group B ( P < 0. 05 ). The m edian PFS of patientswith exon 21 mutation in group A was 8. 9 m onths, rem arkably higher than 7. 0 months in group B ( P <0. 0 1 ). For patients with exon 19 m utation, the m edian OS did not significantly differ between groups A and B( P > 0. 0 5 ). The m edian PFS of patients with exon 21 mutation in group A was 8. 9 m onths, rem arkably higherthan 7. 0 months in group B ( P < 0. 0 1 ). For patients with exon 21 m utation, the m edian OS in group A was26. 7 m onths, significantly longer compared with 23. 8 months in group B ( P < 0. 0 1 ) . For NSCLC patientswith exon 19 and 21 m utation, the incidence of tolerable hypertension and album inuria in group A was significantlyhigher than that in group B ( both P < 0. 05 ). Conclusions Bevacizumab in com bination with EGFRTKIserves as a novel option in the managem ent of advanced NSCLC with EG FR m utation, especially those withexon 21 mutation. The PFS and OS of patients receiving bevacizumab com bined with EGFR-TKI are prolongedcom pared with those treated with EGFR-TKI alone.