摘要
目的尼妥珠单抗为人源化表皮生长因子受体(epidermal growth factor receptor,EGFR)单克隆抗体,能提高放化疗的敏感性。基因突变状态阴性非小细胞肺癌(non-small cell lung cancer,NSCLC)缺乏有效的靶向治疗药物,EGFR过表达在肺癌中常见。本研究探讨一线应用尼妥珠单抗联合同期放化疗治疗表达EGFR,但驱动基因阴性的局部晚期NSCLC(locally advanced non-small cell lung cancer,LA-NSCLC)患者的疗效及不良反应。方法纳入2015-05-01-2019-04-30佛山市南海区人民医院肿瘤科收治经组织病理确诊ⅢA、ⅢB期62例NSCLC患者,驱动基因阴性,免疫组织化学检测EGFR表达阳性,随机数字表法分为对照组和观察组。对照组30例,采用调强适形放疗(intensity modulated conformal radiotherapy,IMRT)及同期和序贯化疗;观察组32例,除上述治疗外,每周静脉滴入尼妥珠单抗200mg,共7次。近期疗效评价总有效率(CR+PR)和疾病控制率(CR+PR+SD);远期疗效评价中位无进展生存期(progressionfree survival,PFS)和中位生存期(overall survival,OS);观察不良反应。结果观察组和对照组总有效率(over all response rate,ORR)分别为71.9%(23/32)和46.7%(14/30),差异有统计学意义,χ^2=4.089,P=0.043;疾病控制率(disease control rate,DCR)分别为90.6%(29/32)和70.0%(21/30),差异有统计学意义,χ^2=4.220,P=0.040;中位PFS分别为13.0(95%CI:11.994~14.006)和10.0个月(95%CI:8.810~11.190),HR=2.831,95%CI:1.597~5.020,P<0.001;中位OS分别为35(95%CI:31.733~38.267)和29个月(95%CI:28.261~29.739),HR=3.378,95%CI:1.836~6.215,P<0.001。2组EGFR表达、肺鳞癌和腺癌病理类型的DCR比较差异均无统计学意义;2组常见化疗药物引起的不良反应均可耐受,无Ⅲ级以上肺毒性反应;观察组和对照组Ⅲ级食管炎反应率分别为6.2%(2/32)和3.3%(1/30),2组比较差异无统计学意义,Z=-0.070,P=0.944。结论尼妥珠单抗联合IMRT及同期化疗一线治疗表达EGFR的局部晚期NSCLC较单纯放化疗更有效,不良反应低,有必要进一步扩大样本量及延长随访时间观察肺癌组织病理类型、EGFR表达和尼妥珠单抗疗效之间的远期关系。
OBJECTIVE Nimotuzumab is a humanized monoclonal antibody against epidermal growth factor receptor(EGFR),which can improve the sensitivity of radiotherapy and chemotherapy.There are limited treatment options for non-small cell lung cancer(NSCLC)without driver mutations.Studies show that EGFR is commonly overexpressed in NSCLC.We conducted this perspective study to assess the safety and efficacy of nimotuzumab combined with concurrent chemoradiotherapy in locally advanced NSCLC(LA-NSCLC)with EGFR expression and negative driver mutations.METHODS A total of 62 patients with stage Ⅲ NSCLC with EGFR expression and negative driver mutations were enrolled from May 1,2015 to April 30,2019 at Nanhai People’s Hospital of Foshan City.They were randomized to receive intensity modulated conformal radiotherapy(IMRT)and chemotherapy(n=30)or the same CRT plus weekly nimotuzumab for 7 weeks(n=32).The primary endpoint was overall response rate(ORR)and disease control rate(DCR).Key secondary endpoints included progression-free survival(PFS),overall survival(OS),and rates of adverse events.RESULTS ORR and DCR were significantly higher with CRT plus nimotuzumab than CRT alone [(71.9%(23/32)vs46.7%(14/30),χ^2=4.089,P=0.043;90.6%(29/32)vs 70.0%(21/30),χ^2=4.220,P=0.040].The median PFS was13.0 months for CRR plus nimotuzumab and 10.0 months for CRT alone(HR=2.831,95%CI:1.597-5.020,P<0.001),while the median OS was 35 months and 29 months respectively(HR=3.378,95%CI:1.836-6.215,P<0.001).There were no difference in the expression of EGFR detected by immunohistochemistry and in the DCR of lung squamous cell carcinoma and pathological type of adenocarcinoma between the two groups.There was no significant difference in the adverse events between the two groups without gradeⅢandⅣradiation pneumonitis.The gradeⅢesophagitis were 6.2%(2/32)and 3.3%(1/30)respectively in CRT with nimotuzumab group and CRT group without significant difference(Z=-0.070,P=0.944).CONCLUSIONS Combination of nimotuzumab and concurrent IMRT and chemotherapy is well tolerated and more effective as first-line for locally advanced NSCLC with EGFR expression than chemoradiotherapy alone.These encouraging results should be confirmed to study the relationship between the pathological type of lung cancer,the expression of EGFR and nimotuzumab in a larger study.
作者
唐武兵
陈永发
潘兴喜
伍楚蓉
袁燕玲
杨文
TANG Wu-bing;CHEN Yong-fa;PAN Xing-xi;WU Chu-rong;YUAN Yan-ling;YANG Wen(First Department of Oncology,Nanhai People's Hospital of Foshan City,Foshan 528200,P.R.China;Second School of Clinical Medicine,Southern Medical University,Foshan 528200,P.R.China)
出处
《中华肿瘤防治杂志》
CAS
北大核心
2020年第13期1075-1080,1093,共7页
Chinese Journal of Cancer Prevention and Treatment
基金
广东省佛山市科技局医学类科技攻关项目(2016AB000702)
佛山市科技创新项目(2016AG100492)
佛山市“十三五”重点专科建设项目(FSZDZK135042)
佛山市南海区“十三五”高水平重点专科建设项目。
关键词
非小细胞肺癌
放射治疗
化学治疗
尼妥珠单抗
靶向治疗
表皮生长因子受体
non-small cell lung cancer
radiotherapy
chemotherapy
Nimotuzumab
targeted therapy
epidermal growth factor receptor
