EGFR-TKIs或联合化疗一线治疗77例晚期肺腺癌临床分析

目的随着肺癌靶向治疗耐药问题的出现,靶向治疗与传统化疗联合成为研究热点。本研究对比表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)联合化疗或单药一线治疗驱动表皮生长因子受体(epidermal growth factor receptor,EGFR)基因阳性晚期肺腺癌的临床疗效及安全性差异,筛选联合治疗优势人群。方法回顾性收集2016-12-01-2018-12-01河南省人民医院收治的初治晚期EGFR(+)肺腺癌77例,依据治疗方案分为联合组和单药组。联合组36例采用培美曲塞+铂类方案化疗,同步口服靶向药物;单药组41例口服EGFR-TKIs。观察随访其治疗后临床疗效及不良反应。采用Kaplan-Meier法行生存分析,Cox回归模型进行多因素分析。结果治疗3个月后联合组客观有效率(objective response rate,ORR)为66.7%(24/36),与单药组53.7%(22/41)相比,差异无统计学意义,χ^2=1.349,P=0.246。疾病控制率(disease control rate,DCR)联合组为100.0%(36/36),单药组为97.6%(40/41),差异无统计学意义,P=1.000。随访截至2019-06-30,总体中位无进展生存期(median progression-free survival,mPFS)为11.5个月,其中联合组mPFS为12个月(95%CI:9.864~14.136),单药组为8个月(95%CI:2.981~13.019),联合组PFS明显优于单药组,差异有统计学意义,χ^2=4.469,P=0.035。胸腔内转移(M1a期)亚组,2组间mPFS差异有统计学意义(HR=0.389,95%CI:0.173~0.874,χ^2=5.873,P=0.015)。联合组血液系统及消化系统不良反应事件发生率更高,差异有统计学意义,P<0.05。2组不良反应均集中在Ⅰ~Ⅱ级,均可耐受。结论 EGFR(+)肺腺癌一线治疗中,1代EGFR-TKIs同步联合培美曲塞+铂类化疗可改善患者PFS,在转移程度较低的M1a期患者中,这种优势更突出。联合治疗增加不良反应事件发生率,但均符合预期并可耐受。

Clinical study of epidermal growth factor receptor-tyrosine kinase inhibitors with or without chemotherapy for advanced lung adenocarcinoma

OBJECTIVE With the emergence of resistance in targeted therapy for lung cancer,recent studies have focused on the combination of targeted therapy and traditional chemotherapy.The objective of this study was to investigate the clinical efficacy and safety which first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)in combination with or without chemotherapy in EGFR(+)lung adenocarcinomas,screening for the advantageous groups of combination therapy.METODES A total of 77 patients of newly diagnosed advanced EGFR(+)lung adenocarcinoma admitted to Henan Provincial People’s Hospital from December 1 st,2016 to December 1 st,2018 were retrospectively enrolled in this study.Thirty-six patients received pemetrexed combined with platinum regimen chemotherapy plus EGFR-TKIs were divided into the combination group and 41 patients received EGFR-TKIs as single drug were monotherapy group.The clinical efficacy and adverse reactions of the two groups were observed after treatment.KaplanMeier method was used for survival analysis,and Cox regression model was used for multivariate analysis.RESUITS The objective response rate(ORR)of the combined group was 66.7%(24/36)and 53.7%(22/41)of the monotherapy group.The disease control rate(DCR)was 100.0%in the combination group and 97.6%(40/41)of the monotherapy group.No statistically significant difference were observed both in ORR(χ^2=1.349,P=0.246)and DCR(P=1.000).At the end of follow up,June 30,2019,the median progression-free survival were significantly longer in the combination group than in the monotherapy groupPFS:12 months(95%CI:9.864-14.136)vs 8 months(95%CI:2.981-13.019),χ^2=4.469,P=0.035];especially for those in status of M1 a(HR=0.389,95%CI:0.173-0.874,χ^2=5.873,P=0.015).The incidence of adverse events in the blood system and digestive system was higher in the combination group,and the difference was statistically significant(P<0.05).Adverse reactions were concentrated in gradesⅠ-Ⅱin both groups and were tolerable.CONCULSIONS In the first-line treatment of EGFR(+)lung adenocarcinoma,the concurrent generation of EGFR-TKIs plus pemetrexed combined with platinum regimen chemotherapy significantly improved the PFS,especially for those with lower metastasis degree,such as patients in M1 astage.Combination-therapy increased the incidence of adverse events,but all were expected and tolerable.