标准与规范丨表皮生长因子受体酪氨酸激酶抑制剂治疗非小细胞肺癌中国专家共识（2025版）

二、EGFR基因检测的适用范围

临床问题1：NSCLC患者EGFR基因检测的适用范围是什么？ 推荐意见1：ⅠB~Ⅳ期肺腺癌患者，应该在诊断的同时常规进行EGFR基因突变检测；对于有腺癌成分或者不吸烟、经小标本活检诊断为非腺癌的NSCLC患者也建议行EGFR基因突变检测（1类推荐）。ⅠA期肺腺癌患者可以不进行EGFR基因突变检测（3类推荐）。 证据总结：不同种族NSCLC患者EGFR基因突变阳性率差异很大，尤其是肺腺癌患者。亚裔肺腺癌患者EGFR基因突变的阳性率较高，一项中国人群的研究结果显示，晚期肺腺癌患者EGFR基因敏感突变阳性的比例为46.7% ［ 7 ］ ，而西方人群肺腺癌中EGFR基因敏感突变阳性率为10% ［ 13 ］ 。对于病理类型为非腺癌的NSCLC患者，如鳞癌、腺鳞癌、大细胞癌等也存在EGFR基因敏感突变，但发生率不高 ［ 14-16 ］ 。除病理类型和种族外，女性和从不吸烟者更易发生EGFR基因敏感突变 ［ 13 ］ 。EGFR基因突变检测对NSCLC患者的治疗策略有重要指导意义。因此，对于ⅠB~Ⅳ期肺腺癌患者，应该在诊断的同时常规进行EGFR基因突变检测；对于伴有腺癌成分或者不吸烟、经小标本活检诊断为非腺癌的NSCLC患者也可以进行EGFR基因突变检测。对于ⅠA期肺腺癌患者，通常认为手术切除后不需要进行辅助治疗，因此这部分患者可以不进行EGFR基因突变检测。临床常用的EGFR基因检测方法包括Sanger测序法、实时定量PCR和二代测序法，具体检测方法可参考《非小细胞肺癌分子病理检测临床实践指南（2024版）》 ［ 17 ］ 。研究表明，合并TP53等基因突变会影响EGFR基因敏感突变NSCLC患者EGFR-TKI的治疗效果，因此，优先选择包括EGFR基因在内的多基因二代测序检测，以提高穿刺标本的使用效率 ［ 18 , 19 ］ 。

三、EGFR基因敏感突变阳性局部晚期或转移性NSCLC患者的一线治疗

临床问题2：EGFR基因敏感突变阳性NSCLC患者的一线治疗选择有什么？ 推荐意见2：EGFR基因敏感突变阳性局部晚期或转移性NSCLC患者的一线治疗推荐药物包括吉非替尼、埃克替尼、阿法替尼、厄洛替尼、达可替尼、奥希替尼、阿美替尼、伏美替尼、贝福替尼、奥希替尼+化疗、瑞厄替尼、瑞齐替尼、佐利替尼、利厄替尼、兰泽替尼+埃万妥单抗（按照NMPA批准时间排序），优先推荐第3代EGFR-TKI单药治疗、奥希替尼+化疗、兰泽替尼+埃万妥单抗。（1类推荐） 证据总结：已经获得NMPA批准上市的EGFR-TKI见 表2 。第1代EGFR-TKI吉非替尼、厄洛替尼和埃克替尼以及第2代EGFR-TKI阿法替尼均开展了与化疗对比一线治疗NSCLC患者的Ⅲ期临床研究，结果显示，EGFR突变阳性NSCLC患者的中位疾病无进展生存期（progression-free survival，PFS）均得到延长，中位PFS为10.9~13.1个月 ［ 20-30］ 。第2代EGFR-TKI阿法替尼和达可替尼均开展了与吉非替尼对比一线治疗EGFR基因敏感突变阳性NSCLC患者的Ⅲ期临床研究，结果显示，阿法替尼和达可替尼治疗的中位PFS均得到延长，中位PFS为11.0~14.7个月 ［ 31-34 ］ 。尽管阿法替尼和达可替尼与吉非替尼对比显示出了更好的疗效，但无论是总体还是≥3级不良反应的发生率，阿法替尼和达可替尼均较吉非替尼有所升高，因此在应用时应注意相关不良反应的处理。 第3代EGFR-TKI奥希替尼、阿美替尼、伏美替尼、贝福替尼、瑞厄替尼、瑞齐替尼和利厄替尼分别与第1代EGFR-TKI对比用于EGFR基因敏感突变阳性晚期NSCLC患者一线治疗的临床研究均取得了阳性结果。FLAURA研究将奥希替尼与第1代EGFR-TKI（吉非替尼或厄洛替尼）分别用于EGFR 19del或EGFR L858R突变阳性局部晚期或转移性NSCLC患者的一线治疗，结果显示，奥希替尼显著延长患者的中位PFS（18.9比10.2个月， HR=0.46，95%CI：0.37~0.57，P

四、EGFR基因敏感突变阳性局部晚期或转移性期NSCLC患者的后线治疗

临床问题3：EGFR基因敏感突变阳性NSCLC患者的后线治疗选择有什么？ 推荐意见3：虽然目前第3代EGFR-TKI已经广泛应用于EGFR基因敏感突变阳性Ⅳ期NSCLC患者的一线治疗，但是仍有患者将第1、2代EGFR-TKI作为一线治疗的药物选择，对于这部分患者建议在疾病进展时重新进行肿瘤组织和（或）外周血基因检测，若EGFR T790M突变阳性，推荐后线应用第3代EGFR-TKI奥希替尼、阿美替尼、伏美替尼、贝福替尼、瑞齐替尼、瑞厄替尼和利厄替尼治疗（1类推荐）；对于一线应用第1、2代EGFR-TKI治疗进展后无EGFR T790M突变和一线应用第3代EGFR-TKI的患者，二线治疗推荐信迪利单抗+贝伐珠单抗+培美曲塞+顺铂（非鳞癌，1类推荐）、依沃西单抗+培美曲塞+卡铂（非鳞癌，1类推荐）、埃万妥单抗+培美曲塞+卡铂（1类推荐）；对于EGFR-TKI治疗进展且伴有间质-上皮转化因子（mesenchymal-epithelial transition factor，MET）扩增的患者，二线治疗可以选择奥希替尼+赛沃替尼（1类推荐）；三线治疗推荐安罗替尼（1类推荐）、芦康沙妥珠单抗（2A类推荐）。也可以根据耐药基因的具体情况尝试应用针对相应靶点的靶向药物治疗（3类推荐）。 证据总结：对第1、2代EGFR-TKI获得性耐药机制已经有相当数量的研究结果，其中约50%的患者耐药是由EGFR T790M基因突变引起的 ［ 49 ］ 。多项临床研究结果显示，EGFR T790M耐药突变阳性的晚期NSCLC患者，后线应用奥希替尼、阿美替尼、伏美替尼、贝福替尼、瑞齐替尼、利厄替尼和瑞厄替尼均取得了良好的临床疗效。AURA3研究结果显示，奥希替尼治疗继发EGFR T790M突变阳性局部晚期或转移性NSCLC的客观缓解率（objective response rate，ORR）（71%比31%， OR=5.39，95% CI：3.47~8.48， P

五、EGFR基因敏感突变阳性Ⅲ期不可切除NSCLC患者的巩固治疗

临床问题4：EGFR基因敏感突变阳性Ⅲ期不可切除NSCLC患者的巩固治疗选择有什么？ 推荐意见4：对于EGFR基因敏感突变阳性、Ⅲ期不可切除、根治性放化疗后未出现疾病进展的NSCLC患者，推荐进行奥希替尼或阿美替尼巩固治疗。（1类推荐） 证据总结：LAURA研究纳入了216例EGFR基因敏感突变阳性、Ⅲ期不可切除、根治性放化疗后未出现疾病进展的NSCLC患者，按2∶1随机分配接受奥希替尼或安慰剂治疗，结果显示奥希替尼组的中位PFS显著延长（39.1比5.6个月， HR=0.16，95% CI：0.10~0.24， P

七、EGFR基因敏感突变阳性NSCLC患者的辅助治疗

临床问题6：EGFR基因敏感突变阳性NSCLC患者的辅助治疗选择有什么？ 推荐意见6：对于EGFR基因敏感突变阳性、有辅助治疗指征的NSCLC患者，术后可进行埃克替尼、奥希替尼或阿美替尼辅助治疗。（1类推荐） 证据总结：EGFR基因敏感突变阳性NSCLC患者的辅助EGFR-TKI治疗目前已有一些前瞻性临床研究证据。EVIDENCE研究纳入了322例根治术后Ⅱ~ⅢA期EGFR基因敏感突变阳性NSCLC患者，按1∶1随机分配接受2年埃克替尼或4周期长春瑞滨+顺铂方案辅助治疗，结果显示，埃克替尼组较长春瑞滨+顺铂方案组可显著延长患者的中位无病生存期（disease-free interval，DFS）（47.0比22.1个月， HR=0.36，95% CI：0.24~0.55， P 图1 表皮生长因子受体（EGFR）驱动基因阳性非小细胞肺癌（NSCLC）治疗流程图 注：TKI为酪氨酸激酶抑制剂；CNS为中枢神经系统；MET为间质-上皮转化因子 目前，对于携带EGFR基因经典突变的NSCLC患者的前瞻性研究结果相对较多，而EGFR基因非经典突变的探索仍主要来自经典第1、2、3代EGFR-TKI回顾性或事后分析的小样本研究结果，亟需加强对EGFR基因非经典突变NSCLC患者的新药研发，以期造福此类患者。与此同时，第3代EGFR-TKI耐药后的治疗策略仍面临挑战，需要不断探索和更新。此外，部分EGFR-TKI在巩固治疗、术后辅助治疗以及联合化疗一线治疗的疗效已有阳性结果，未来需要更多研究明确其他EGFR-TKI辅助治疗以及联合化疗的疗效。 本专家共识基于文献和专家的临床经验制订，不具有法律效力，仅供临床医师参考，其内容也将随着医学证据的不断更新而更新，实施时应结合临床具体情况综合考虑。 本共识制订专家委员会名单（按姓氏汉语拼音排序） 顾问： 孙燕（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室） 牵头专家： 石远凯（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室） 专家组成员： 艾斌（北京医院肿瘤内科）；仓顺东（河南省人民医院肿瘤内科）；陈军（天津医科大学总医院胸外科）；陈骏（大连医科大学附属第二医院肿瘤内科）；崔久嵬（吉林大学白求恩第一医院肿瘤内科）；董晓荣（华中科技大学同济医学院附属协和医院肿瘤内科）；顾康生（安徽医科大学第一附属医院肿瘤内科）；桂琳（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；郭其森（山东省肿瘤医院肿瘤内科）；郭人花（南京医科大学第一附属医院肿瘤科）；韩晓红（中国医学科学院北京协和医院临床药理中心 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；郝学志（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；何志勇（福建省肿瘤医院肿瘤内科）；胡兴胜（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；胡长路（安徽省肿瘤医院肿瘤内科）；黄鼎智（天津市肿瘤医院肿瘤内科）；黄建安（苏州大学附属第一医院呼吸与危重症医学科）；郏博（北京大学肿瘤医院胸部肿瘤内一科）；林冬梅（北京大学肿瘤医院病理科）；林华（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院病案室）；刘鹏（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；刘尚梅（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院病理科）；刘晓晴（解放军总医院第五医学中心肿瘤内科）；刘雨桃（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；刘云鹏（中国医科大学附属第一医院肿瘤内科）；柳江（新疆维吾尔自治区人民医院肿瘤内科）；马克威（吉林大学白求恩第一医院肿瘤内科）；马丽（北京胸科医院肿瘤内科）；潘跃银（安徽省立医院肿瘤内科）；沈波（江苏省肿瘤医院肿瘤内科）；石远凯（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；史美祺（江苏省肿瘤医院肿瘤内科）；宋霞（山西省肿瘤医院呼吸内科）；宋之乙（中日友好医院胸外科）；孙燕（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；陶丹（重庆大学附属肿瘤医院肿瘤放射治疗中心）；陶云霞（徐州医科大学附属医院肿瘤内科）；汪麟（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；王彩莲（东南大学附属中大医院肿瘤科）；王长利（天津医科大学附属肿瘤医院肺部肿瘤科）；王东（陆军军医大学大坪医院肿瘤科）；王华庆（天津市人民医院肿瘤内科）；王佳蕾（复旦大学附属肿瘤医院胸部肿瘤内科）；王孟昭（中国医学科学院北京协和医院呼吸与危重症医学科）；王征（北京医院病理科）；王子平（北京大学肿瘤医院胸部肿瘤内一科）；吴世凯（北京大学第一医院肿瘤内科）；伍钢（华中科技大学同济医学院附属协和医院肿瘤中心）；信涛（哈尔滨医科大学附属第二医院肿瘤内科）；邢镨元（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；杨建良（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；杨磊（甘肃省肿瘤医院呼吸内科）；杨晟（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；杨树军（河南省肿瘤医院肿瘤内科）；杨向红（中国医科大学附属第二医院病理科）；姚煜（西安交通大学附属第一医院肿瘤内科）；于国华（潍坊市人民医院肿瘤内科）；藏爱民（河北大学附属医院肿瘤内科）；曾瑄（中国医学科学院 北京协和医院病理科）；张贺龙（空军军医大学唐都医院肿瘤内科）；张俊萍（山西白求恩医院肿瘤内科）；张兰军（中山大学附属肿瘤医院胸外科）；张力（中国医学科学院北京协和医院呼吸与危重症医学科）；张沂平（浙江省肿瘤医院肿瘤内科）；赵仁（宁夏医科大学总医院肿瘤医院放疗科）；赵琼［树兰（杭州）医院胸部肿瘤中心］；钟巧凤（福建省肿瘤医院胸部肿瘤内科）；周生余（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室）；周宗玫（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院放疗科） 学术秘书： 陈馨蕊、高菇云、黄莉玲、唐乐、谢同济、谢祖成、杨梦薇、朱豪华（国家癌症中心 国家肿瘤临床医学研究中心 中国医学科学院北京协和医学院肿瘤医院内科 重大疾病创新药早期临床试验评价关键技术北京市重点实验室） 利益冲突 所有作者声明不存在利益冲突 参考文献（下滑查看）： [1]Bray F , Laversanne M , Sung H ,et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024,74(3):229-263. DOI: 10.3322/caac.21834 . [2]Han B , Zheng R , Zeng H ,et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Cent, 2024,4(1):47-53. DOI: 10.1016/j.jncc.2024.01.006 . [3]Thai AA , Solomon BJ , Sequist LV ,et al. Lung cancer[J]. Lancet, 2021,398(10299):535-554. DOI: 10.1016/S0140-6736(21)00312-3 . [4]Shi Y , Zhang X , Wu G ,et al. Treatment strategy, overall survival and associated risk factors among patients with unresectable stage ⅢB/Ⅳ non-small cell lung cancer in China (2015-2017): a multicentre prospective study[J]. Lancet Reg Health West Pac, 2022,23:100452. DOI: 10.1016/j.lanwpc.2022.100452 . [5]Zhong Q , Tao Y , Chen H ,et al. The changing landscape of anti-lung cancer drug clinical trials in the Mainland of China from 2005 to 2020[J]. Lancet Reg Health West Pac, 2021,11:100151. DOI: 10.1016/j.lanwpc.2021.100151 . [6]Shi Y , Au JS , Thongprasert S ,et al. A prospective, molecular epidemiology study of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology (PIONEER)[J]. J Thorac Oncol, 2014,9(2):154-162. DOI: 10.1097/JTO.0000000000000033 . [7]Shi Y , Li J , Zhang S ,et al. Molecular epidemiology of EGFR mutations in Asian patients with advanced non-small-cell lung cancer of adenocarcinoma histology-the Mainland of China subset analysis of the PIONEER study[J]. PLoS One, 2015,10(11):e0143515. DOI: 10.1371/journal.pone.0143515 . [8]Cho J , Choi SM , Lee J ,et al. The association of EGFR mutations with stage at diagnosis in lung adenocarcinomas[J]. PLoS One, 2016,11(11):e0166821. DOI: 10.1371/journal.pone.0166821 . [9]Hu X , Han B , Gu A ,et al. A single-arm, multicenter, safety-monitoring, phase Ⅳ study of icotinib in treating advanced non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2014,86(2):207-212. DOI: 10.1016/j.lungcan.2014.08.014 . [10]Gou LY , Wu YL . Prevalence of driver mutations in non-small-cell lung cancers in the People′s Republic of China[J]. Lung Cancer (Auckl), 2014,5:1-9. DOI: 10.2147/LCTT.S40817 . [11]官绍年,陈迎珠,卓明磊,等. 非小细胞肺癌EGFR基因突变检测的临床应用进展[J]. 临床检验杂志, 2020, (2):130-136. DOI: 10.13602/j.cnki.jcls.2020.02.13 . [12]中国医疗保健国际交流促进会肿瘤内科学分会,中国医师协会肿瘤医师分会. Ⅳ期非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂中国治疗指南(2023版)[J]. 中华医学杂志, 2023,103(40):3160-3173. DOI: 10.3760/cma.j.cn112137-20230505-00725 . [13]Dacic S , Shuai Y , Yousem S ,et al. Clinicopathological predictors of EGFR/KRAS mutational status in primary lung adenocarcinomas[J]. Mod Pathol, 2010,23(2):159-168. DOI: 10.1038/modpathol.2009.154 . [14]Ho HL , Kao HL , Yeh YC ,et al. The importance of EGFR mutation testing in squamous cell carcinoma or non-small cell carcinoma favor squamous cell carcinoma diagnosed from small lung biopsies[J]. Diagn Pathol, 2019,14(1):59. DOI: 10.1186/s13000-019-0840-2 . [15]Xu J , Zhang Y , Jin B ,et al. Efficacy of EGFR tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations in China[J]. J Cancer Res Clin Oncol, 2016,142(6):1325-1330. DOI: 10.1007/s00432-016-2133-4 . [16]Song X , Wang Z . Clinical efficacy evaluation of tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations[J]. Onco Targets Ther, 2017,10:3119-3122. DOI: 10.2147/OTT.S134523 . [17]国家病理质控中心,中华医学会病理学分会,中华医学会肿瘤学分会肺癌学组,等. 非小细胞肺癌分子病理检测临床实践指南(2024版)[J]. 中华病理学杂志, 2024,53(10):981-995. DOI: 10.3760/cma.j.cn112151-20240527-00338 . [18]Hong S , Gao F , Fu S ,et al. Concomitant genetic alterations with response to treatment and epidermal growth factor receptor tyrosine kinase inhibitors in patients with EGFR-mutant advanced non-small cell lung cancer[J]. JAMA Oncol, 2018,4(5):739-742. DOI: 10.1001/jamaoncol.2018.0049 . [19]Zhao S , Zhang Z , Zhan J ,et al. Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer[J]. BMC Med, 2021,19(1):223. DOI: 10.1186/s12916-021-02089-z . [20]Mok TS , Wu YL , Thongprasert S ,et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J]. N Engl J Med, 2009,361(10):947-957. DOI: 10.1056/NEJMoa0810699 . [21]Fukuoka M , Wu YL , Thongprasert S ,et al. Biomarker analyses and final overall survival results from a phase Ⅲ, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)[J]. J Clin Oncol, 2011,29(21):2866-2874. DOI: 10.1200/JCO.2010.33.4235 . [22]Wu YL , Saijo N , Thongprasert S ,et al. Efficacy according to blind independent central review: post-hoc analyses from the phase Ⅲ, randomized, multicenter, IPASS study of first-line gefitinib versus carboplatin/paclitaxel in Asian patients with EGFR mutation-positive advanced NSCLC[J]. Lung Cancer, 2017,104:119-125. DOI: 10.1016/j.lungcan.2016.11.022 . [23]Shi YK , Wang L , Han BH ,et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study[J]. Ann Oncol, 2017,28(10):2443-2450. DOI: 10.1093/annonc/mdx359 . [24]Zhou C , Wu YL , Chen G ,et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study[J]. Lancet Oncol, 2011,12(8):735-742. DOI: 10.1016/S1470-2045(11)70184-X . [25]Zhou C , Wu YL , Chen G ,et al. Final overall survival results from a randomised, phase Ⅲ study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802)[J]. Ann Oncol, 2015,26(9):1877-1883. DOI: 10.1093/annonc/mdv276 . [26]Sequist LV , Yang JC , Yamamoto N ,et al. Phase Ⅲ study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations[J]. J Clin Oncol, 2013,31(27):3327-3334. DOI: 10.1200/JCO.2012.44.2806 . [27]Yang JC , Wu YL , Schuler M ,et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials[J]. Lancet Oncol, 2015,16(2):141-151. DOI: 10.1016/S1470-2045(14)71173-8 . [28]Schuler M , Wu YL , Hirsh V ,et al. First-line afatinib versus chemotherapy in patients with non-small cell lung cancer and common epidermal growth factor receptor gene mutations and brain metastases[J]. J Thorac Oncol, 2016,11(3):380-390. DOI: 10.1016/j.jtho.2015.11.014 . [29]Wu YL , Zhou C , Hu CP ,et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial[J]. Lancet Oncol, 2014,15(2):213-222. DOI: 10.1016/S1470-2045(13)70604-1 . [30]Yang JC , Wu YL , Schuler M ,et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials[J]. Lancet Oncol, 2015,16(2):141-151. DOI: 10.1016/S1470-2045(14)71173-8 . [31]Park K , Tan EH , O′Byrne K ,et al. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial[J]. Lancet Oncol, 2016,17(5):577-589. DOI: 10.1016/S1470-2045(16)30033-X . [32]Paz-Ares L , Tan EH , O′Byrne K ,et al. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase Ⅱb LUX-Lung 7 trial[J]. Ann Oncol, 2017,28(2):270-277. DOI: 10.1093/annonc/mdw611 . [33]Wu YL , Cheng Y , Zhou X ,et al. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2017,18(11):1454-1466. DOI: 10.1016/S1470-2045(17)30608-3 . [34]Mok TS , Cheng Y , Zhou X ,et al. Updated overall survival in a randomized study comparing Dacomitinib with Gefitinib as first-line treatment in patients with advanced non-small-cell lung cancer and EGFR-activating mutations[J]. Drugs, 2021,81(2):257-266. DOI: 10.1007/s40265-020-01441-6 . [35]Soria JC , Ohe Y , Vansteenkiste J ,et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer[J]. N Engl J Med, 2018,378(2):113-125. DOI: 10.1056/NEJMoa1713137 . [36]Ramalingam SS , Vansteenkiste J , Planchard D ,et al. Overall survival with Osimertinib in untreated, EGFR-mutated advanced NSCLC[J]. N Engl J Med, 2020,382(1):41-50. DOI: 10.1056/NEJMoa1913662 . [37]Lu S , Dong X , Jian H ,et al. AENEAS: a randomized phase Ⅲ trial of aumolertinib versus gefitinib as first-line therapy for locally advanced or metastaticnon-small-cell lung cancer with EGFR exon 19 deletion or L858R mutations[J]. J Clin Oncol, 2022,40(27):3162-3171. DOI: 10.1200/JCO.21.02641 . [38]Shi Y , Chen G , Wang X ,et al. Furmonertinib (AST2818) versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small-cell lung cancer (FURLONG): a multicentre, double-blind, randomised phase 3 study[J]. Lancet Respir Med, 2022,10(11):1019-1028. DOI: 10.1016/S2213-2600(22)00168-0 . [39]Shi Y , Chen G , Wang X ,et al. Patient-reported outcomes for the phase 3 FURLONG study of furmonertinib versus gefitinib as first-line therapy for Chinese patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer[J]. Lancet Reg Health West Pac, 2024,48:101122. DOI: 10.1016/j.lanwpc.2024.101122 . [40]Lu S , Zhou J , Jian H ,et al. Befotertinib (D-0316) versus icotinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer: a multicentre, open-label, randomised phase 3 study[J]. Lancet Respir Med, 2023,11(10):905-915. DOI: 10.1016/S2213-2600(23)00183-2 . [41]Zhou C , Xiong A . A phase Ⅲ study of rilertinib versus gefitinib as first-line therapy for patients with locally advanced or metastatic EGFR-mutated NSCLC[J]. J Thorac Oncol, 2024,19(10):S11. DOI: 10.1016/j.jtho.2024.09.027 . [42]Shi Y , Guo Y , Li X ,et al. Reziv ertinib versus gefitinib as first-line therapy for patients with EGFR-mutated locally advanced or metastatic non-small-cell lung cancer (REZOR): a multicentre, double-blind, randomised, phase 3 study [J]. Lancet Respir Med, 2025,13(4):327-337. DOI: 10.1016/S2213-2600(24)00417-X . [43]Shi Y , Wu L , Ji Y ,et al. Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial[J]. Lancet Respir Med, 2025. DOI: 10.1016/S2213-2600(25)00121-3 . [44]Planchard D , Jänne PA , Cheng Y ,et al. Osimertinib with or without chemo therapy in EGFR-mutated advanced NSCLC [J]. N Engl J Med, 2023,389(21):1935-1948. DOI: 10.1056/NEJMoa2306434 . [45]Valdiviezo N , Okamoto I , Hughes BG ,et al. 4O first-line (1L) osimertinib (osi)±platinum-pemetrexed in EGFR-mutated (EGFRm) advanced NSCLC: FLAURA2 post-progression outcomes[J]. ESMO Open, 2024,9:102583. [46]Lu S , Hu J , Chen J ,et al. Aumolertinib with or without chemotherapy as first line treatment in locally advanced or metastatic NSCLC with sensitizing EGFR mutations (AENEAS2)[J]. Cancer Research, 2025,85(8_Supplement_2):CT053-CT. [47]Cho BC , Lu S , Felip E ,et al. Amivantamab plus Lazertinib in previously untreated EGFR-mutated advanced NSCLC[J]. N Engl J Med, 2024,391(16):1486-1498. DOI: 10.1056/NEJMoa2403614 . [48]Yang JCH , Kim YJ , Lee SH ,et al. Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: final overall survival (OS) from the phase Ⅲ MARIPOSA study[J]. J Thorac Oncol, 2025,20(3):S6-S8. [49]Sequist LV , Waltman BA , Dias-Santagata D ,et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors[J]. Sci Transl Med, 2011,3(75):75ra26. DOI: 10.1126/scitranslmed.3002003 . [50]Mok TS , Y-L W , M-J A ,et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer[J]. N Engl J Med, 2017,376(7):629-640. DOI: 10.1056/NEJMoa1612674 . [51]Papadimitrakopoulou VA , Mok TS , Han JY ,et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis[J]. Ann Oncol, 2020,31(11):1536-1544. DOI: 10.1016/j.annonc.2020.08.2100 . [52]Lu S , Wang Q , Zhang G ,et al. Efficacy of Aumolertinib (HS-10296) in Patients With Advanced EGFR T790M+NSCLC: updated post-national medical products administration approval results from the APOLLO registrational trial[J]. J Thorac Oncol, 2022,17(3):411-422. DOI: 10.1016/j.jtho.2021.10.024 . [53]Lu S , Wang Q , Zhang G ,et al. Final results of APOLLO study: overall survival (OS) of aumolertinib in patients with pretreated EGFR T790M-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)[J]. Ann Oncol, 2021,32:S962. [54]Shi Y , Hu X , Zhang S ,et al. Efficacy, safety, and genetic analysis of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small-cell lung cancer: a phase 2b, multicentre, single-arm, open-label study[J]. Lancet Respir Med, 2021,9(8):829-839. DOI: 10.1016/S2213-2600(20)30455-0 . [55]Lu S , Zhang Y , Zhang G ,et al. Efficacy and safety of Befotertinib (D-0316) in patients with EGFR T790M-mutated NSCLC that had progressed after prior EGFR tyrosine kinase inhibitor therapy: a phase 2, multicenter, single-arm, open-label study[J]. J Thorac Oncol, 2022,17(10):1192-1204. DOI: 10.1016/j.jtho.2022.06.002 . [56]Shi Y , Wu S , Wang K ,et al. Efficacy and safety of Rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC: a phase 2b study[J]. J Thorac Oncol, 2022,17(11):1306-1317. DOI: 10.1016/j.jtho.2022.08.015 . [57]Shi Y , Li B , Wu L ,et al. Efficacy and safety of Limertinib (ASK120067) in patients with locally advanced or metastatic EGFR Thr790Met-mutated NSCLC: a multicenter, single-arm, phase 2b study[J]. J Thorac Oncol, 2022,17(10):1205-1215. DOI: 10.1016/j.jtho.2022.05.011 . [58]Xiong A , Ren S , Liu H ,et al. Efficacy and safety of SH-1028 in patients with EGFR T790M-positive NSCLC: a multicenter, single-arm, open-label, phase 2 trial[J]. J Thorac Oncol, 2022,17(10):1216-1226. DOI: 10.1016/j.jtho.2022.06.013 . [59]Lu S , Wu L , Jian H ,et al. Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial[J]. Lancet Respir Med, 2023,11(7):624-636. DOI: 10.1016/S2213-2600(23)00135-2 . [60]Investigators HS , Fang W , Zhao Y ,et al. Ivonescimab plus chemotherapy in non-small cell lung cancer with EGFR variant: a randomized clinical trial[J]. JAMA, 2024,332(7):561-570. DOI: 10.1001/jama.2024.10613 . [61]Passaro A , Wang J , Wang Y ,et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase Ⅲ MARIPOSA-2 study[J]. Ann Oncol, 2024,35(1):77-90. DOI: 10.1016/j.annonc.2023.10.117 . [62]Lu S , Wang J , Yang N ,et al. Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and amplification advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): results from a randomized phase 3 SACHI study[J]. J Clin Oncol, 2025,43(17_suppl):LBA8505-LBA. [63]Fang W , Li X , Wang Q ,et al. Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial[J]. BMJ, 2025,389:e085680. DOI: 10.1136/bmj-2025-085680 . [64]Han B , Li K , Wang Q ,et al. Effect of Anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER 0303 phase 3 randomized clinical trial[J]. JAMA Oncol, 2018,4(11):1569-1575. DOI: 10.1001/jamaoncol.2018.3039 . [65]Lu S , Kato T , Dong X ,et al. Osimertinib after chemoradiotherapy in stage Ⅲ EGFR-mutated NSCLC[J]. N Engl J Med, 2024,391(7):585-597. DOI: 10.1056/NEJMoa2402614 . [66]Yu J , Meng X , Ge H ,et al. Aumolertinib maintenance after chemoradiotherapy in stage Ⅲ non-small-cell lung cancer: interim results of the phase Ⅲ study (POLESTAR)[J]. J Thorac Oncol, 2024,19(10):S6-S7. [67]Jung HA , Woo SY , Lee SH ,et al. The different central nervous system efficacy among gefitinib, erlotinib and afatinib in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer[J]. Transl Lung Cancer Res, 2020,9(5):1749-1758. DOI: 10.21037/tlcr-20-379 . [68]Park SJ , Kim HT , Lee DH ,et al. Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation[J]. Lung Cancer, 2012,77(3):556-560. DOI: 10.1016/j.lungcan.2012.05.092 . [69]Iuchi T , Shingyoji M , Sakaida T ,et al. Phase Ⅱ trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma[J]. Lung Cancer, 2013,82(2):282-287. DOI: 10.1016/j.lungcan.2013.08.016 . [70]Yang JJ , Zhou C , Huang Y ,et al. Icotinib versus whole-brain irradiation in patients with EGFR-mutant non-small-cell lung cancer and multiple brain metastases (BRAIN): a multicentre, phase 3, open-label, parallel, randomised controlled trial[J]. Lancet Respir Med, 2017,5(9):707-716. DOI: 10.1016/S2213-2600(17)30262-X . [71]Zhou Q , Yu Y , Xing L ,et al. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: the phase 3 EVEREST trial[J]. Med, 2025,6(1):100513. DOI: 10.1016/j.medj.2024.09.002 . [72]Reungwetwattana T , Nakagawa K , Cho BC ,et al. CNS response to Osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors in patients with untreated EGFR-mutated advanced non-small-cell lung cancer[J]. J Clin Oncol, 2018:JCO2018783118. DOI: 10.1200/JCO.2018.78.3118 . [73]Wu YL , Ahn MJ , Garassino MC ,et al. CNS efficacy of Osimertinib in patients with T790M-positive advanced non-small-cell lung cancer: data from a randomized phase Ⅲ trial (AURA3)[J]. J Clin Oncol, 2018,36(26):2702-2709. DOI: 10.1200/JCO.2018.77.9363 . [74]Jänne PA , Planchard D , Kobayashi K ,et al. CNS Efficacy of Osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer[J]. J Clin Oncol, 2024,42(7):808-820. DOI: 10.1200/JCO.23.02219 . [75]Lu S , Dong X , Jian H ,et al. Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase Ⅲ trial (AENEAS)[J]. Cancer Commun (Lond), 2024,44(9):1005-1017. DOI: 10.1002/cac2.12594 . [76]Shi Y , Chen G , Wang X ,et al. Central nervous system efficacy of Furmonertinib (AST2818) versus gefitinib as first-line treatment for EGFR-mutated NSCLC: results from the FURLONG study[J]. J Thorac Oncol, 2022,17(11):1297-1305. DOI: 10.1016/j.jtho.2022.07.1143 . [77]Hu X , Zhang S , Ma Z ,et al. Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies[J]. BMC Med, 2023,21(1):164. DOI: 10.1186/s12916-023-02865-z . [78]Yang S , Wu S , Zhao Y ,et al. Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: a pooled analysis of two clinical studies[J]. Lung Cancer, 2023,180:107194. DOI: 10.1016/j.lungcan.2023.107194 . [79]Yang J , Kim SW , Kim DW ,et al. Osimertinib in patients with epidermal growth factor receptor mutation-positive non-small-cell lung cancer and leptomeningeal metastases: the BLOOM study[J]. J Clin Oncol, 2020,38(6):538-547. DOI: 10.1200/JCO.19.00457 . [80]Ahn MJ , Chiu CH , Cheng Y ,et al. Osimertinib for patients with leptomeningeal metastases associated with EGFR T790M-positive advanced NSCLC: the AURA leptomeningeal metastases analysis[J]. J Thorac Oncol, 2020,15(4):637-648. DOI: 10.1016/j.jtho.2019.12.113 . [81]Lee J , Choi Y , Han J ,et al. Osimertinib improves overall survival in patients with EGFR-mutated NSCLC with leptomeningeal metastases regardless of T790M mutational status[J]. J Thorac Oncol, 2020,15(11):1758-1766. DOI: 10.1016/j.jtho.2020.06.018 . [82]Fan C , Jiang Z , Teng C ,et al. Efficacy and safety of intrathecal pemetrexed for TKI-failed leptomeningeal metastases from EGFR+NSCLC: an expanded, single-arm, phase Ⅱ clinical trial[J]. ESMO Open, 2024,9(4):102384. DOI: 10.1016/j.esmoop.2024.102384 . [83]Fan C , Zhao Q , Li L ,et al. Efficacy and safety of intrathecal pemetrexed combined with Dexamethasone for treating tyrosine kinase inhibitor-failed leptomeningeal metastases from EGFR-mutant NSCLC-a prospective, open-label, single-arm phase 1/2 clinical trial (unique identifier: ChiCTR1800016615)[J]. J Thorac Oncol, 2021,16(8):1359-1368. DOI: 10.1016/j.jtho.2021.04.018 . [84]吴熙,李峻岭,肖建平,等. 甲氨蝶呤鞘内注射化疗对肺癌脑膜转移的疗效分析[J]. 癌症进展, 2019,18(8):914-917, 932. DOI: 10.11877/j.issn.1672-1535.2019.17.08.12 . [85]He J , Su C , Liang W ,et al. Icotinib versus chemotherapy as adjuvant treatment for stage Ⅱ-ⅢA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial[J]. Lancet Respir Med, 2021,9(9):1021-1029. DOI: 10.1016/S2213-2600(21)00134-X . [86]Liu YT , Hao XZ , Liu DR ,et al. Icotinib as adjuvant treatment for stage Ⅱ-ⅢA lung adenocarcinoma patients with EGFR mutation (ICWIP Study): study protocol for a randomised controlled trial[J]. Cancer Manag Res, 2020,12:4633-4643. DOI: 10.2147/CMAR.S240275 . [87]Wu YL , Tsuboi M , He J ,et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer[J]. N Engl J Med, 2020,383(18):1711-1723. DOI: 10.1056/NEJMoa2027071 . [88]Herbst RS , Wu YL , John T ,et al. Adjuvant Osimertinib for resected EGFR-mutated stage IB-IIIA non-small-cell lung cancer: updated results from the phase Ⅲ randomized ADAURA trial[J]. J Clin Oncol, 2023,41(10):1830-1840. DOI: 10.1200/JCO.22.02186 . [89]Tsuboi M , Herbst RS , John T ,et al. Overall survival with Osimertinib in resected EGFR-mutated NSCLC[J]. N Engl J Med, 2023,389(2):137-147. DOI: 10.1056/NEJMoa2304594 . [90]Cheng Y , Zhang X , Wu L ,et al. Aumolertinib as adjuvant therapy in patients with stage Ⅱ-ⅢB EGFR-mutated NSCLC after complete tumor resection: a randomized, double-blind, placebo-controlled, phase 3 trial (ARTS)[J]. Cancer Research, 2025,85(8_Supplement_2):CT126-CT. [91]Riess JW , Gandara DR , Frampton GM ,et al. Diverse EGFR exon 20 insertions and co-occurring molecular alterations identified by comprehensive genomic profiling of NSCLC[J]. J Thorac Oncol, 2018,13(10):1560-1568. DOI: 10.1016/j.jtho.2018.06.019 . [92]Low JL , Lim SM , Lee JB ,et al. Advances in the management of non-small-cell lung cancer harbouring EGFR exon 20 insertion mutations[J]. Ther Adv Med Oncol, 2023,15:17588359221146131. DOI: 10.1177/17588359221146131 . [93]Yasuda H , Park E , Yun CH ,et al. Structural, biochemical, and clinical characterization of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in lung cancer[J]. Sci Transl Med, 2013,5(216):216ra177. DOI: 10.1126/scitranslmed.3007205 . [94]Gonzalvez F , Vincent S , Baker TE ,et al. Mobocertinib (TAK-788): a targeted inhibitor of EGFR exon 20 in sertion mutants in non-small cell lung cancer [J]. Cancer Discov, 2021,11(7):1672-1687. DOI: 10.1158/2159-8290.CD-20-1683 . [95]Robichaux JP , Le X , Vijayan R ,et al. Structure-based classification predicts drug response in EGFR-mutant NSCLC[J]. Nature, 2021,597(7878):732-737. DOI: 10.1038/s41586-021-03898-1 . [96]Robichaux JP , Elamin YY , Tan Z ,et al. Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer[J]. Nat Med, 2018,24(5):638-646. DOI: 10.1038/s41591-018-0007-9 . [97]Yang M , Xu X , Cai J ,et al. NSCLC harboring EGFR exon-20 insertions after the regulatory C-helix of kinase domain responds poorly to known EGFR inhibitors[J]. Int J Cancer, 2016,139(1):171-176. DOI: 10.1002/ijc.30047 . [98]Wang M , Fan Y , Sun M ,et al. Sunvozertinib for patients in China with platinum-pretreated locally advanced or metastatic non-small-cell lung cancer and EGFR exon 20 insertion mutation (WU-KONG6): single-arm, open-label, multicentre, phase 2 trial[J]. Lancet Respir Med, 2024,12(3):217-224. DOI: 10.1016/S2213-2600(23)00379-X . [99]Yang JCH , Chiu CH , Hsu PC ,et al. Efficacy and safety of sunvozertinib in treatment naïve NSCLC patients with EGFR exon20 insertion mutations[J]. J Clin Oncol, 2023,41(16_suppl):9073. [100]Zhou C , Tang KJ , Cho BC ,et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions[J]. N Engl J Med, 2023,389(22):2039-2051. DOI: 10.1056/NEJMoa2306441 . [101]Harrison PT , Vyse S , Huang PH . Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020,61:167-179. DOI: 10.1016/j.semcancer.2019.09.015 . [102]Floc′h N , Lim S , Bickerton S ,et al. Osimertinib, an irreversible next-generation EGFR tyrosine kinase inhibitor, exerts antitumor activity in various preclinical NSCLC models harboring the uncommon EGFR mutations G719X or L861Q or S768I[J]. Mol Cancer Ther, 2020,19(11):2298-2307. DOI: 10.1158/1535-7163.MCT-20-0103 . [103]Kohsaka S , Nagano M , Ueno T ,et al. A method of high-throughput functional evaluation of EGFR gene variants of unknown significance in cancer[J]. Sci Transl Med, 2017,9(416). DOI: 10.1126/scitranslmed.aan6566 . [104]Kobayashi Y , Mitsudomi T . Not all epidermal growth factor receptor mutations in lung cancer are created equal: perspectives for individualized treatment strategy[J]. Cancer Sci, 2016,107(9):1179-1186. DOI: 10.1111/cas.12996 . [105]Yang JC , Schuler M , Popat S ,et al. Afatinib for the treatment of NSCLC harboring uncommon EGFR mutations: a database of 693 cases[J]. J Thorac Oncol, 2020,15(5):803-815. DOI: 10.1016/j.jtho.2019.12.126 . [106]Yang JC , Sequist LV , Geater SL ,et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6[J]. Lancet Oncol, 2015,16(7):830-838. DOI: 10.1016/S1470-2045(15)00026-1 . [107]Cho JH , Lim SH , An HJ ,et al. Osimertinib for patients with non-small-cell lung cancer harboring uncommon EGFR mutations: a multicenter, open-label, phase Ⅱ trial (KCSG-LU15-09)[J]. J Clin Oncol, 2020,38(5):488-495. 10.1200/JCO.19.00931 . [108]Bar J , Peled N , Schokrpur S ,et al. Uncommon EGFR mutations: international case series on efficacy of Osimertinib in real-life practice in first-line setting (UNICORN)[J]. J Thorac Oncol, 2023,18(2):169-180. DOI: 10.1016/j.jtho.2022.10.004 . 版权归中华医学会所有。 未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。 除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。 长按识别二维码，访问官网，免费下载 主管：中国科学技术协会 主办：中华医学会 编辑：中华医学杂志编辑委员会 地址：100052，北京市西城区东河沿街69号正弘大厦 网址：http://www.nmjc.net.cn 总编辑：曹雪涛 编辑部主任：吕相征 本刊微信：nmjc1915 新浪微博：中华医学杂志 官方网站：http://nmjc.net.cn 想分享到“朋友圈”？请点击右上角“…”按钮； 有话对我们说？请直接点击文章右下方“写留言” 发送吧！ 封面图来源于AI合成，如有侵权请联系删除

推荐意见与 GRADE 证据分级

相关指南

• EGFR 20外显子插入突变非小细胞肺癌规范化诊疗中国专家共识（2024版） · 肿瘤内科 2024
• 0bda96368841127b94ed2d7e042cf1827304490130628008__【肺癌-2025】中国驱动基因阳性非小细胞肺癌脑转移 临床诊疗指南（2025版） · 肿瘤内科 2025
• 老年晚期肺癌治疗专家共识（2025版） · 肿瘤内科 2025
• 驱动基因阳性非小细胞肺癌脑膜转移临床诊疗中国专家共识（2026版） · 肿瘤内科 2026
• 肺结核与肺癌共病诊疗专家共识 · 感染与传染病
• Ⅳ期原发性肺癌中国治疗指南（2024版） · 肿瘤内科 2024
• 专家共识丨表皮生长因子受体酪氨酸激酶抑制剂治疗非小细胞肺癌中国专家共识（2025版） · 呼吸科 2025
• 中华医学会肺癌临床诊疗指南（2025版） · 肿瘤内科 2025