EGFR敏感突变的晚期肺腺癌一线化疗与吉非替尼联合治疗的随机对照研究

doi:10.3969/j.issn.1007-3969.2015.10.001

中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (10): 761-767.doi: 10.3969/j.issn.1007-3969.2015.10.001

EGFR敏感突变的晚期肺腺癌一线化疗与吉非替尼联合治疗的随机对照研究

金　波，张岩巍，韩宝惠，牛艳洁，董　瑜，储天晴，顾爱琴

上海交通大学附属胸科医院呼吸内科，上海 200030

出版日期:2015-10-30 发布日期:2015-12-17
通信作者: 韩宝惠　E-mail:xkyyhan@gmail.com
基金资助:
上海市科委重点课题(11411951200)。

Randomized controlled trial of chemotherapy plus gefitinib as first-line treatment for patients with advanced EGFR mutation-positive lung adenocarcinoma

JIN Bo, ZHANG Yanwei, HAN Baohui, NIU Yanjie, DONG Yu, CHU Tianqing, GU Aiqin

Department of Respiratory medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China

Published:2015-10-30 Online:2015-12-17
Contact: HAN Baohui E-mail: xkyyhan@gmail.com

摘要/Abstract

摘要： 背景与目的：表皮生长因子受体(epidermal growth factor receptor，EGFR)敏感突变的晚期肺腺癌患者目前标准一线治疗方案为表皮生长因子受体-酪氨酸激酶抑制剂(epithelial growth factor receptor-tyrosine kinase inhibitor，EGFR-TKI)单药治疗。该研究探索化疗联合吉非替尼与单用化疗、单用吉非替尼在EGFR基因敏感突变的晚期肺腺癌一线治疗中的疗效及安全性比较。方法：本研究共纳入了61例EGFR基因敏感突变(19外显子缺失突变或21外显子L858R点突变)、PS 0～1分的初治晚期肺腺癌患者，并用随机数字法随机分成3组。A组20例，给予AC方案化疗(培美曲塞500 mg/m²，第1天；卡铂AUC 5，第1天)联合口服吉非替尼(250 mg/d，第5~21天)，每4周为1个周期，最多6个周期，然后每4周进行1次培美曲塞单药联合吉非替尼口服(用药方法及剂量同前)维持治疗；B组20例，给予AC方案化疗(培美曲塞500 mg/m²，第1天；卡铂AUC 5，第1天)，每4周为1个周期，最多6个周期，然后每4周进行1次培美曲塞单药维持治疗；C组21例，口服吉非替尼治疗(250 mg/d)。3组的治疗均持续至患者出现疾病进展或出现无法耐受的不良反应或死亡。研究的主要终点为中位无进展生存时间(progression-free survival，PFS)和12个月PFS率，次要终点为总体缓解率、安全性/不良反应。结果：随访中A、C组各失访1例。A组患者中位PFS为20.1个月(95%CI：18.0～22.2个月)，B组患者中位PFS为5.5个月(95%CI：3.9～7.2个月)，C组患者中位PFS为9.8个月(95%CI：6.8～12.8个月)。A组的12个月PFS率为78.9%，B组为15.0%，C组为40.0%。总体缓解率：A组为84.2%，B组为35.0%，C组为65.0%。安全性方面，严重不良反应的发生率A组为36.8%，B组为30.0%，C组为5.0%。最常见的3～4度不良反应为中性粒细胞减少(A组3例、B组4例)、乏力(A组2例、B组2例)及肝功能损害(A组2例、C组1例)。结论：一线接受化疗与吉非替尼联合治疗的EGFR敏感突变的晚期肺腺癌患者PFS更长。长期的生存结果仍在进一步随访中。

关键词: 肺腺癌, 表皮生长因子受体突变, 化学治疗, 吉非替尼

Abstract: Background and purpose: For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activating EGFR gene mutation. Methods: This study included 61 patients with lung adenocarcinoma harboring an activating EGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m², d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then received pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events. Results: Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9- 7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C). Conclusion: Among patients with EGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

Key words: Lung adenocarcinoma, EGFR mutation, Chemotherapy, Gefitinib

金　波,张岩巍,韩宝惠,等. EGFR敏感突变的晚期肺腺癌一线化疗与吉非替尼联合治疗的随机对照研究[J]. 中国癌症杂志, 2015, 25(10): 761-767.

JIN Bo, ZHANG Yanwei, HAN Baohui, et al. Randomized controlled trial of chemotherapy plus gefitinib as first-line treatment for patients with advanced EGFR mutation-positive lung adenocarcinoma[J]. China Oncology, 2015, 25(10): 761-767.

[1]	胡冠男, 陈　雷, 周良平, 周正荣 . 肺恶性黑色素瘤合并肺腺癌1例并文献复习[J]. 中国癌症杂志, 2021, 31(7): 647-650.
[2]	胡雅琼, 白　俊, 陈　琳, 陈新璐, 张丽萍, 周丹丹, 王　玉, 尹崇高, 李洪利, 刘雨清 . miR-625-5p通过靶向调控PRKACA促进肺腺癌细胞的增殖和侵袭[J]. 中国癌症杂志, 2021, 31(6): 447-454.
[3]	彭子珊, 孔　辉, 鲍　真, 赵红杏, 刘　鑫, 卢韶华. 83例多发肺腺癌患者的临床病理学特征分析[J]. 中国癌症杂志, 2021, 31(5): 408-418.
[4]	施茂林, 柏玉娣, 王超, 李思琪, 周代君, 彭晶晶, 孙非凡, 李东, 张涛 . PD-L1表达对晚期肺腺癌患者培美曲塞化疗效果的影响及其机制[J]. 中国癌症杂志, 2021, 31(4): 308-316.
[5]	王晓栋 , 周丹丹 , 张丽萍 , 郑　荃 , 牟青杰 , 尹崇高 , 李洪利 . FAM83A在肺腺癌组织中高表达且促进肺腺癌细胞的侵袭和转移[J]. 中国癌症杂志, 2020, 30(8): 586-592.
[6]	颜　芳, 应明真, 陈龙佩, 傅　强. 白蛋白结合型紫杉醇联合奈达铂一线治疗晚期食管癌患者的临床观察[J]. 中国癌症杂志, 2020, 30(8): 632-635.
[7]	高志强,王韡旻,蔡雨晴,秦若琰,顾爱琴,熊丽纹,韩宝惠,姜丽岩,施春雷 . 奥希替尼治疗62例晚期肺腺癌患者的临床疗效观察[J]. 中国癌症杂志, 2019, 29(10): 809-814.
[8]	宋玉芝,吴晓琳,甄婵军,等. 99例结外NK/T细胞淋巴瘤预后分析[J]. 中国癌症杂志, 2018, 28(9): 698-705.
[9]	王升平,付怡,刘权,等. 乳腺癌患者肺内孤立性结节CT征象：肺原发性腺癌和转移性乳腺癌的鉴别[J]. 中国癌症杂志, 2018, 28(6): 411-418.
[10]	戴曦,李国平,杨小琼,等. Lyn激酶对肺腺癌EGFR下游信号通路的调节作用研究[J]. 中国癌症杂志, 2018, 28(1): 43-49.
[11]	田希贵,刘德森,汪元玉,等. 腺癌与其他类型非小细胞肺癌术后临床特点的差异及预后因素分析[J]. 中国癌症杂志, 2017, 27(3): 227-232.
[12]	刘红柳,杨家梅. 培美曲塞单药或联合吉非替尼治疗EGFR-TKI耐药后晚期非小细胞肺癌临床观察[J]. 中国癌症杂志, 2017, 27(2): 135-139.
[13]	沈旭霞,王　瑞,孙艺华,等. 融合基因阳性肺腺癌的病理组织学特征及与砂粒体的相关性研究[J]. 中国癌症杂志, 2016, 26(8): 655-661.
[14]	周　娟,贲素琴. 培美曲塞与多西他赛联合铂类一线治疗晚期肺腺癌的疗效比较[J]. 中国癌症杂志, 2015, 25(9): 671-676.
[15]	周欣,李晓琴,王秀丽,等. 吉非替尼获得性耐药的非小细胞肺癌患者临床特点[J]. 中国癌症杂志, 2015, 25(3): 222-229.

EGFR敏感突变的晚期肺腺癌一线化疗与吉非替尼联合治疗的随机对照研究

Randomized controlled trial of chemotherapy plus gefitinib as first-line treatment for patients with advanced EGFR mutation-positive lung adenocarcinoma

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价