ALK融合基因阳性晚期肺腺癌克唑替尼耐药后治疗的效果分析  

Clinical efficacy of regimens in patients with anaplastic lymphoma kinase fusion gene-positive pulmonary adenocarcinoma of acquired crizotinib resistance

作　　者：吴标[1] 庄武[1] 黄诚[1] 郑晓彬[1] 尹一 张晶[1] 蒋侃[1] 苗茜[1] WU Biao;ZHUANG Wu;HUANG Cheng;ZHENG Xiaobin;YIN Yi;ZHANG Jing;JIANG Kan;MIAO Qian(Department of Thoracic Oncology,Fujian Cancer Hospital,Cancer Hospital Affiliated to Fujian Medical University,Fuzhou 350014,China)

机构地区：[1]福建省肿瘤医院福建医科大学附属肿瘤医院胸部肿瘤内科,福州350014

出　　处：《临床肿瘤学杂志》2018年第8期716-720,共5页Chinese Clinical Oncology

基　　金：福建省医学创新课题资助项目(2017-CXB-1);福建省自然科学基金项目(2017J01263)

摘　　要：目的探讨间变性淋巴瘤激酶(ALK)融合基因阳性晚期肺腺癌经克唑替尼治疗失败后不同治疗方案的效果和不良反应。方法收集本院2014年1月至2017年10月诊治的ALK融合基因阳性经克唑替尼治疗耐药的晚期肺腺癌患者65例,其中接受ALK抑制剂治疗13例,全身化疗52例(培美曲塞联合铂类23例、紫杉醇联合铂类10例、长春瑞滨联合铂类3例、吉西他滨联合铂类5例、培美曲塞单药5例和多西他赛单药6例),2个周期后分别采用RECIST 1.1版与NCI-CTC4.0版标准评价疗效和不良反应,根据随访数据分析不同治疗方案的预后情况。结果全组均可评价疗效,客观有效率(RR)为46.2%,疾病控制率(DCR)为73.8%。使用2代ALK抑制剂者的RR优于全身化疗者(76.9%vs.38.5%,P=0.013);全身化疗者中,含培美曲塞方案的RR优于不含培美曲塞方案(53.6%vs.20.8%,P=0.016),含铂方案的DCR优于不含铂单药治疗(80.5%vs.36.4%,P=0.013)。全组中位无进展生存期(PFS)为4.0个月(95%CI:3.2~4.8个月),使用2代ALK抑制剂者的中位PFS为10.0个月,优于全身化疗者的4.0个月(P=0.003)。全组中位总生存期(OS)为19.0个月(95%CI:17.4~20.6个月),使用2代ALK抑制剂者的中位OS为25.0个月,优于全身化疗者的18.5个月(P=0.012);EGOG评分0~1分的中位OS为19.5个月,优于2分的17.0个月(P=0.004);临床分期为ⅢB期的中位OS为26.5个月,优于Ⅳ期的18.5个月(P=0.046)。结论 ALK融合基因阳性晚期肺腺癌患者克唑替尼耐药后,给予2代ALK抑制剂的治疗效果较好,EGOG评分0~1分和临床分期ⅢB期患者的生存期更长。Objective To investigate the efficacy of different regimens in patients with anaplasticlymphoma kinase （ALK） fu.sion gene.positive pulmonary adenocarcinoma of a cquired crizotinib resistance. Methods From January 2014 to October 2017, 65 pa.tients with advanced ALK fusion gene.positive pulmonary adenocarcinoma of acquired crizotinib resistance in our hospital were enrolled.According to the treatment regimes, 13 cases received ALK inhibitors and remaining 52 cases received systemic chemotherapy, inclu.ding 23 cases of pemetrexed plus platinum, 10 cases of paclitaxel plus platinum, 3 cases of vinorelbine and platinum, 5 cases of gem.citabine and platinum, 5 cases of pemetrexed alone and 6 cases of docetaxel alone. After 2 cycles, the efficacy and adverse reactionswere evaluated by RECIST 1.1 and NCI.CTC 4.0, and the prognosis of different treatment schemes was analyzed according to the follow.up data. Results All patients were evaluable for efficacy with the objective response rate （ORR） of 46.2% and the disease con.trol rate （DCR） of 73.8%. Patints receiving the second generation of ALK inhibitor showed better RR than cytotoxic drugs （76.9% vs.38. 5%, P= 0.013）. For chemotherapy group, pemetrexed.contained regimens had better RR than non.pemetrexed regimens （53. 6%vs. 20. 8%, P= 0.016）, and platinum.contained regimens were better than monotherapy in DCR （80. 5% vs.36. 4%,P= 0.013）. The progression free survival（PFS）and overall survival （OS） of all patients were 4.0 months（95%CI： 3. 2.4. 8） and 19.0 months（95%CI： 17. 4.20. 6）, respectively. The second generation of ALK inhibitor was better than cytotoxic drugs for PFS （10.0 months vs. 4.0months,P= 0.003） and OS （25.0 months vs.18. 5 months, P = 0.012）. ECOG 0.1 （19. 5 months vs.17.0 months,P = 0.004） andclinical stage ⅢB were favorite factors for OS （26. 5 months vs. 18. 5 months, P= 0.046） comparing with ECOG 2 and stage Ⅳ, re.spectively. Conclusion The second generation of ALK inhibitor presented str

关 键 词：肺腺癌 间变性淋巴瘤激酶(ALK) 化学治疗 药物耐药 

分 类 号：R734.2[医药卫生—肿瘤]