国产吉非替尼与原研药一线治疗EGFR阳性晚期NSCLC对比研究

目的一代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)吉非替尼是表皮生长因子受体EGFR敏感基因突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线治疗药物。本研究对比分析国产吉非替尼与原研药一线治疗EGFR敏感突变19外显子Del和21(L858R)点突变]的临床疗效及安全性,探讨国产吉非替尼与原研药疗效的一致性。方法选取2017-03-01-2019-01-31淮北市人民医院收治的经病理学确诊的晚期EGFR突变的NSCLC患者70例,采用随机数字表法随机分为国产吉非替尼组35例和原研药组35例,4周为1个周期,每2个周期评价疗效。观察2组的有效率(response rate,RR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)、毒副作用及预后等。采用SPSS 19.0对数据进行统计分析。结果国产吉非替尼组RR为65.7%,原研药组为71.4%,χ~2=0.265,P=0.607。DCR国产吉非替尼组为82.9%,原研药组为91.4%,χ~2=1.148,P=0.284。中位PFS国产吉非替尼组为9.1个月,原研药组为9.5个月,χ~2=0.021,P=0.884。RR国产吉非替尼组19外显子Del的为78.3%,原研药组为83.3%,χ~2=0.005,P=0.943。DCR国产吉非替尼组19外显子Del的为91.3%,原研药组为95.8%,χ~2=0.001,P=0.970。RR国产吉非替尼组21(L858R)点突变的为41.7%,原研药组为45.5%,χ~2=0.034,P=0.885;DCR国产吉非替尼组21(L858R)点突变的为66.7%,原研药组为81.8%,差异无统计学意义,χ~2=0.683,P=0.408。2组患者中19外显子Del的RR为80.9%,21(L858R)点突变的为43.5%,χ~2=10.009,P=0.002;19外显子Del的DCR为93.6%,21(L858R)点突变的为73.9%,χ~2=5.351,P=0.021。2组患者中19外显子Del的中位PFS为11.7个月,21(L858R)点突变的为8.6个月,差异有统计学意义,χ~2=10.798,P=0.001。2组主要的毒副作用是腹泻和皮疹,多为Ⅰ~Ⅱ度,差异无统计学意义,P>0.05。结论国产吉非替尼与原研药治疗EGFR敏感突变的晚期NSCLC疗效及不良反应相当,19外显子Del的患者较21(L858R)点突变的患者疗效更佳。

Comparative study on domestic Gefitinib and original drug in the first-line treatment of advanced non-small cell lung cancer with EGFR mutation

OBJECTIVE Gefitinib,the first generation Epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs),has become a first-line treatment of advanced non-small cell lung cancer(NSCLC)with EGFR sensitive mutation.This study aimed to compare and analyze the clinical efficacy and safety of domestic Gefitinib and original drug in first-line treatment of advanced NSCLC patients with EGFR sensitive mutation19 exon deletion and 21(L858 R)point mutation].METHODS From March 1 st 2017 to January 31 st 2019,70 advanced cases of pathologically confirmed NSCLC with EGFR mutation were involved in the study at our institution.Patients were randomly assigned into two groups,35 cases for domestic Gefitinib and 35 cases for original drug.The medication was orally taken for 4 weeks in a cycle,and the efficacy was evaluated for every 2 cycles.The response rate(RR),disease control rates(DCR),progression-free survival(PFS),toxic side effects of the two groups were observed.RESULTS The RR of domestic Gefitinib group and original study group were 65.7% and 71.4%(χ~2=0.265,P=0.607),respectively.The DCR were 82.9% and 91.4%(χ~2=1.148,P=0.284),respectively.The median PFS of two groups were 9.1 months and 9.5 months(χ~2=0.021,P=0.884),respectively.The RR of the 19 exon deletion in domestic Gefitinib and original drug group were 78.3% and83.3%(χ~2=0.005,P=0.943),respectively.The DCR were 91.3%and 95.8%(χ~2=0.001,P=0.970),respectively.The RR of 21(L858 R)point mutation were 41.7% and 45.5% (χ~2=0.034,P=0.885),respectively,and the DCR were66.7% and 81.8%(χ~2=0.683,P=0.408),respectively.There were not statistical differences between the two groups.For all cases,the RR was 80.9%in patients with 19 exon Del and 43.5%in patients with 21(L858 R)point mutation(χ~2=10.009,P=0.002).The DCR was 93.6%in patients with 19 exon Del and 73.9%in patients with 21(L858 R)point mutation(χ~2=5.351,P=0.021).The median PFS was 11.7 months in patients with 19 exon Del and 8.6 months in patients with 21(L858 R)point mutation(χ~2=10.798,P=0.001).There were statistical differences between the two groups.The main toxic side effects of two groups were Ⅰ/Ⅱ degree of diarrhea and rashes.There were not statistical differences between the two groups(P>0.05).CONCLUSIONS The efficacy and side effects of domestic Gefitinib are comparable to those of original drug in the treatment of advanced NSCLC patients with EGFR sensitive mutation.The efficacy of 19 exon Del patients is better than that of 21(L858 R)point mutation patients.