盐酸埃克替尼联合全脑放疗治疗非小细胞肺癌脑转移的随机对照研究

A randomized controlled trial of ectatinib hydrochloride combined with whole brain radiotherapy for brain metastasis of non-small cell lung cancer

目的探讨全脑放疗联合盐酸埃克替尼治疗非小细胞肺癌(NSCLC)脑转移的疗效及安全性。方法选取2013年6月～2017年6月共44例脑转移的NSCLC患者,随机分为联合治疗组与单纯放疗组,比较两组间疗效及安全性。结果中位随访18.5个月,联合治疗组及单纯放疗组的mPFS分别为9.3个月及6.6个月(log-rank P=0.006);联合治疗组EGFR突变者及野生型者的mPFS分别为12.2个月和6.5个月(log-rank P=0.002),单纯放疗组EGFR突变者及野生型者的mPFS分别为6.4个月和6.8个月(log-rank P=0.933)。联合治疗组及单纯放疗组的mOS分别为14.2个月及12.6个月(log-rank P=0.035);联合治疗组中EGFR突变者及野生型者的mOS分别为19.1个月和12.7个月(log-rank P=0.006),单纯放疗组EGFR突变者及野生型者的mOS分别为12.6个月和10.4个月(log-rank P=0.449)。两组间的ORR分别为78.3%及47.6%(log-rank P=0.035),DCR分别为91.3%及85.7%(χ2=0.341,P=0.560)。不良反应方面,联合组的皮疹发生率为56.5%,其中3例为3～4级;两组乏力、恶心呕吐、腹泻肝肾损伤、白细胞减少等不良反应均为1～2级,且两组比较差异无统计学意义。结论盐酸埃克替尼联合全脑放疗可提高非小细胞肺癌脑转移患者的客观缓解率,延长中位局部无进展生存期及中位总生存期,患者的不良反应耐受性良好。

Objective To investigate the efficacy and safety of whole brain radiotherapy combined with ectatinib hydrochloride in the treatment of non-small cell lung cancer(NSCLC)brain metastases.Methods A total of 44 patients with brain metastases from NSCLC from June 2013 to June 2017 were randomly divided into combination therapy group and radiotherapy group.The efficacy and safety between the two groups were compared.Results The median follow-up was 18.5 months.The mPFS of the combination therapy group and the radiotherapy group were 9.3 months and 6.6 months,respectively(log-rank P=0.006).The mPFS of the EGFR mutant and wild type in the combination group were 12.2 months and 6.5 months(log-rank P=0.002).The mPFS of EGFR mutants and wild-type patients in the radiotherapy group were 6.4 months and 6.8 months,respectively(log-rank P=0.933).The mOS in the combination therapy group and the radiotherapy group were 14.2 months and 12.6 months,respectively(log-rank P=0.035).The mOS of the EGFR mutant and wild type in the combination group were 19.1 months and 12.7 months,respectively(log-rank P=0.006).The mOS of EGFR mutants and wild-type patients in the radiotherapy group were 12.6 months and 10.4 months,respectively(log-rank P=0.449).The ORR of the two groups was 78.3%and 47.6%,respectively(log-rank P=0.035),and the DCR was 91.3%and 85.7%,respectively(χ^2=0.341,P=0.560).In terms of adverse reactions,the incidence of rash in the combined group was 56.5%,of which 3 cases were grade 3-4.The adverse reactions such as fatigue,nausea and vomiting,diarrhea,liver and kidney damage,and leukopenia were all grade 1-2,and there was no statistically significant difference between the two groups.Conclusion Ectinib hydrochloride combined with whole brain radiotherapy can improve the objective response rate of patients with non-small cell lung cancer with brain metastases,prolong the median local progression-free survival and median overall survival,and the patient's adverse reaction tolerance is good.