埃克替尼治疗晚期肺腺癌的疗效分析

目的:观察埃克替尼治疗晚期肺腺癌的疗效及安全性方法:收集2011年7月至2012年3月我院晚期肺腺癌患者共67例,均给予口服埃克替尼125mg,tid,直至疾病进展或出现无法耐受的不良反心。结果:67例中一线治疗者16例,二线及二线以上治疗者51例,总的客观缓解率为35.8%(24/67),疾病控制率为74.6%(50/67);行EGFR(Epidermal growth factor receptor,表皮生长因子受体)基因检测的18例患者中有15例EGFR基因突变阳性,客观缓解率为60%(9/15),疾病控制率为93.3%(14/15)疗效因素分析显示仅化疗方案数与客观有效率和疾病控制率有关系(P=0.034,P=0.044)。最常见的有不良反应皮疹、腹泻、皮肤瘙痒,发生率分别为20.9%、11.9%、9.0%,程度均较轻(Ⅰ度～Ⅱ度)。结论:埃克替尼治疗晚期肺腺癌,患者能获得较好的疗效及临床获益,且安全性好。     

埃克替尼治疗98例复治EGFR突变阳性的晚期肺腺癌的疗效分析

目的:观察埃克替尼治疗复治表皮生长因子受体(epidermal growth factor receptor,EGFR）敏感突变的晚期肺腺癌患者的疗效及不良反应。方法:收集2011年11月至2016年7月期间一线或多线化疗进展的98例EGFR 敏感突变的晚期肺腺癌患者应用埃克替尼治疗的疗效、不良反应及生存资料。结果:98例既往化疗失败的EGFR基因敏感突变晚期肺腺癌患者中,达到完全缓解（CR）1例（1.0%）,部分缓解（PR）66例（67.3%）,疾病稳定（SD）20例（20.4%）,疾病进展（PD）11例（11.2%）;客观缓解率（ORR）为68.4%（67/98),疾病控制率（DCR）为88.8%（87/98）,中位无进展时间（mPFS）为8.8个月（95%CI:7.1～10.5个月）,中位生存时间（mOS）为15.5个月（95%CI:11.8～19.2个月）。亚组分析中,19外显子缺失突变患者的ORR（82.0% vs 54.2%,P=0.003）、mPFS（11.0个月 vs 6.0个月,P=0.008）及mOS（20.0个月 vs 12.6个月,P=0.016）均优于21外显子L858R突变患者;非脑转移患者的mOS优于脑转移患者（16.0个月 vs 8.0个月,P=0.039）;不吸烟患者的ORR 优于吸烟患者（76.7% vs 55.3%,P=0.023）;不同性别、年龄、肺癌分期、治疗线数、转移器官数对预后的影响均未见差异有统计学意义。不良反应以皮疹、腹泻、肝功能异常为主,经对症处理后症状均可明显缓解。结论:埃克替尼治疗既往化疗失败的EGFR突变阳性的晚期肺腺癌患者取得了确切的疗效,且不良反应发生率低。     

盐酸埃克替尼治疗EGFR突变晚期肺腺癌的预后因素分析

目的 探讨晚期肺腺癌表皮生长因子受体（EGFR）突变患者应用表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）盐酸埃克替尼片治疗与预后的关系。方法 入组河北省胸科医院基因检测提示EGFR19、21基因突变且接受盐酸埃克替尼片治疗的晚期肺腺癌患者,分析其临床特征、EGFR基因突变亚型及不同位点与预后的关系。结果 全组共纳入101例晚期肺腺癌患者,EGFR基因19外显子缺失突变（EGFR Del19）58例,21外显子点突变（EGFR L858R）43例。全组患者客观缓解率达63.4%,中位无疾病进展时间（mPFS）和中位生存时间（mOS）分别为13个月和27个月。EGFR Del19对比EGFRL858R及EGFR19突变746~750位点对比其他突变位点的患者mPFS和mOS均增高。多因素分析显示,转移部位数和有无胸膜转移为OS的独立影响因素（P=0.027, P=0.041）,转移部位数≤3和无胸膜转移组患者的mOS分别为29个月和27个月。结论 盐酸埃克替尼片治疗晚期肺腺癌患者EGFR不同突变亚型和位点总生存差异不显著,转移部位数≤3和无胸膜转移的患者总生存期更长。     

埃克替尼治疗EGFR敏感突变的晚期非小细胞肺癌获益患者的临床分析

背景与目的靶向治疗已经成为晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）治疗中不可或缺的重要手段,表皮生长因子受体（epithelial growth factor receptor, EGFR）的酪氨酸激酶抑制剂（tyrosine kinase inhibitor, TKI）可显著延长晚期携带EGFR基因突变肺癌患者生存期。埃克替尼是我国第一个拥有自主知识产权的EGFR-TKI。本研究旨在探讨埃克替尼治疗EGFR敏感突变的晚期NSCLC获益患者的临床特点,对获益患者[无进展生存时间（progression-free survival, PFS）≥6个月]进行回顾性资料收集并分析相关影响因素。方法收集2011年9月1日-2015年9月30日浙江省肿瘤医院经埃克替尼片治疗的231例EGFR敏感突变的晚期NSCLC获益患者的生存情况。结果经埃克替尼治疗后,一线治疗组1年获益率达67.9%,二线及以上组为53.6%,具有统计学意义（P=0.027）;一线治疗组2年获益率对比二线及以上组亦有统计学差异（18.7%和9.3%,P=0.047）。一线患者和二线及以上患者的中位PFS分别为16.7个月和12.4个月,且差异具有统计学意义（P=0.006）。其中有无脑转移（P=0.010）、埃克替尼治疗时机（P=0.001）、美国东部肿瘤协作组（East-ern Cooperative Oncology Group, ECOG）评分（P=0.001）为影响预后的主要因素。主要不良反应为皮疹51例（22.1%）,腹泻27例（11.7%）。结论埃克替尼是EGFR基因敏感突变的晚期NSCLC患者有效的治疗方案,其优势人群除无脑转移者及ECOG评分好的患者外,一线治疗患者疗效明显优于二线及以上者。敏感突变患者采用埃克替尼可得到较好的临床获益,并具有较好的耐受性。     

埃克替尼一线治疗134例EGFR突变阳性的晚期肺腺癌的疗效分析

摘 要：［目的］ 观察埃克替尼一线治疗EGFR突变阳性的晚期肺腺癌患者的疗效及不良反应。［方法］ 对134例Ⅲb/Ⅳ期EGFR突变阳性的晚期肺腺癌患者应用埃克替尼125mg 每天三次治疗,直至疾病进展或出现不可耐受的不良反应。［结果］ 134例EGFR基因突变阳性晚期肺腺癌患者中,完全缓解(CR)6例（4.5%）,部分缓解(PR)90例（67.2%）,疾病稳定（SD）32例（23.9%）,疾病进展（PD）6例（4.5%)。客观缓解率（ORR)为71.6%(96/134),疾病控制率(DCR)为95.5%（128/134）。中位无进展时间（mPFS）为11.2个月(95%CI：9.8～12.5个月）,OS尚未获得。19外显子缺失突变的ORR 为81.8%,DCR为93.5%,mPFS为11.8个月。21外显子L858R突变患者ORR 为 57.9%,DCR为94.7%,mPFS为10.2个月。19外显子缺失突变的ORR明显优于21外显子L858R突变（81.8% vs 57.9%,P=0.002)。不吸烟患者的ORR优于吸烟患者（77.4% vs 58.5%,P=0.025)。不同性别、年龄、肺癌分期、EGFR突变类型、吸烟状态对mPFS和DCR的影响无统计学差异。主要不良反应为Ⅰ～Ⅱ度的皮疹（44.8%）和腹泻（25.3%）,经对症处理后,患者多可耐受。［结论］ 埃克替尼一线治疗EGFR突变阳性的晚期肺腺癌患者取得了很好的疗效,不良反应的发生率低,且患者多可耐受。     

奥希替尼治疗不同表皮生长因子受体基因突变型晚期肺腺癌疗效分析

目的 分析一代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)耐药后奥希替尼治疗不同EGFR基因突变的晚期肺腺癌临床疗效.方法 回顾性分析2015年1月至2019年10月郑州大学第一附属医院收治的82例EGFR敏感突变且第1代EGFR-TKIs耐药后基因检测T790M突变的晚期肺腺癌患者的临床资料.将50例19外...     

埃克替尼在晚期非小细胞肺癌EGFR状态明确的患者中的疗效分析

背景与目的 埃克替尼是国内第一个口服的表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶受体抑制剂,在体内外实验研究中显示出对非小细胞肺癌的明显抑制作用.Ⅲ期临床研究ICOGEN显示埃克替尼对复治晚期非小细胞肺癌疗效不劣于吉非替尼.本研究探讨在晚期非小细胞肺癌明确EGFR状态的患者中(EGFR野生型和突变型)埃克替尼的疗效和安全性.方法 回顾性分析2011年8月-2012年8月在浙江省肿瘤医院就诊并行埃克替尼治疗的晚期非小细胞肺癌患者,Kaplan-Meier法进行生存分析和比较.结果 49例患者明确了EGFR突变状态并行埃克替尼治疗,49例患者中13例为野生型,36例为突变型.突变患者的客观缓解率和疾病控制率分别为58.3％和88.9％,野生型患者的客观缓解率和疾病控制率分别为7.7％和53.8％.突变和野生型患者的中位无进展生存期为9.5个月和2.2个月(P＜0.001).36例突变患者中一线治疗19例,二线及二线以上患者17例.一线和复治患者的中位无进展生存期(progression-free survival,PFS)分别为9.5个月和8.5个月(P=0.41).突变型患者的中位总生存期(overall survival,OS)尚未达到,野生型患者的OS为12.6个月.患者的不良反应以皮疹和腹泻为主,但多为轻到中度.结论 埃克替尼在EGFR突变患者中的疗效较好,可以作为EGFR突变患者的优选方案.患者的毒副反应多数可以耐受.     

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

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。     

晚期肺腺癌EGFR基因突变状态检测及分析

目的分析晚期肺腺癌表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变率及其与临床特征的相关性。方法收集2010-09-07-2011-07-21首都医科大学附属北京胸科医院收治的晚期初治肺腺癌患者102例,有可供检测的肿瘤组织标本。利用扩增受阻突变系统（amplification refractory mutation system,ARMS）进行EGFR基因突变检测,统计分析EGFR基因突变状态和临床特征的相关性。结果 102例晚期肺腺癌组织中,共检测到EGFR基因突变55例（53.9%）,其中18外显子突变1例（1.0%）,19外显子突变25例（24.5%）,20外显子突变2例（2.0%）,21外显子突变26例（25.5%）,同时存在19和20外显子突变1例（1.0%）。Ⅳ期患者EGFR基因突变率为57.6%（53/92）,高于ⅢB期患者20.0%（1/10）,差异有统计学意义,P=0.041;女性患者EGFR基因突变率56.9%（33/58）高于男性患者的50.0%（22/44）,不吸烟患者EGFR基因突变率58.1%（36/62）高于吸烟患者的36.0%（9/25）,〈65岁患者EGFR基因突变率56.8%（42/74）高于≥65岁患者的46.4%（13/28）,但差异均无统计学意义,P〉0.05。不同取材部位及取材方法之间EGFR基因突变率差异无统计学意义,P〉0.05。结论晚期肺腺癌EGFR基因突变率以Ⅳ期、女性和不吸烟患者较高,但性别及吸烟状态之间的差异无统计学意义。不同的肿瘤活检部位及活检方法之间EGFR基因突变率并无差异。     

Clinical outcomes of EGFR-TKI treatment and genetic heterogeneity in lung adenocarcinoma patients with EGFR mutations on exons 19 and 21

Background: Epidermal growth factor receptor (EGFR) mutations, including a known exon 19 deletion (19 del) and exon 21 L858R point mutation (L858R mutation), are strong predictors of the response to EGFR tyrosine kinase inhibi?tor (EGFR?TKI) treatment in lung adenocarcinoma. However, whether patients carrying EGFR 19 del and L858R muta?tions exhibit different responsiveness to EGFR?TKIs and what are the potential mechanism for this difference remain controversial. This study aimed to investigate the clinical outcomes of EGFR?TKI treatment in patients with EGFR 19 del and L858R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes. Methods: Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858R mutations, 532 received EGFR?TKI treatment and were included in this study. EGFR 19 del and L858R mutations were detected by using denaturing high?performance liquid chromatography (DHPLC). T790M mutation, which is a common resistant mutation on exon 20 of EGFR, was detected by amplification refractory mutation system (ARMS). Next?generation sequencing (NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858R mutations. Results: Of the 532 patients, 319 (60.0%) had EGFR 19 del, and 213 (40.0%) had L858R mutations. The patients with EGFR 19 del presented a significantly higher overall response rate (ORR) for EGFR?TKI treatment (55.2% vs. 43.7%, P = 0.017) and had a longer progression?free survival (PFS) after first?line EGFR?TKI treatment (14.4 vs. 11.4 months,P= 0.034) compared with those with L858R mutations. However, no statistically significant difference in overall survival (OS) was observed between the two groups of patients. T790M mutation status was analyzed in 88 patients before EGFR?TKI treatment and 134 after EGFR?TKI treatment, and there was no significant difference in the co?exist?ence of T790M mutation with EGFR 19 del and L858R mutations before EGFR?TKI treatment (5.6% vs. 8.8%, P = 0.554)or after treatment (24.4% vs. 35.4%, P= 0.176). In addition, 24 patients with EGFR 19 del and 19 with L858R mutations were analyzed by NGS, and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes. Conclusions: Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858R muta?tions. Whether the heterogeneity of tumors with EGFR 19 del and L858R mutations contribute to a therapeutic response difference needs further investigation.     

国产吉非替尼与原研药一线治疗EGFR阳性晚期NSCLC对比研究

目的一代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)吉非替尼是表皮生长因子受体EGFR敏感基因突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线治疗药物。本研究对比分析国产吉非替尼与原研药一线治疗EGFR敏感突变[19外显子Del和21(L858R)点突变]的临床疗效及安全性,探讨国产吉非替尼与原研药疗效的一致性。方法选取2017-03-01-2019-01-31淮北市人民医院收治的经病理学确诊的晚期EGFR突变的NSCLC患者70例,采用随机数字表法随机分为国产吉非替尼组35例和原研药组35例,4周为1个周期,每2个周期评价疗效。观察2组的有效率(response rate,RR)、疾病控制率(disease control rate,DCR)、无进展生存期(progression-free survival,PFS)、毒副作用及预后等。采用SPSS 19.0对数据进行统计分析。结果国产吉非替尼组RR为65.7%,原研药组为71.4%,χ~2=0.265,P=0.607。DCR国产吉非替尼组为82.9%,原研药组为91.4%,χ~2=1.148,P=0.284。中位PFS国产吉非替尼组为9.1个月,原研药组为9.5个月,χ~2=0.021,P=0.884。RR国产吉非替尼组19外显子Del的为78.3%,原研药组为83.3%,χ~2=0.005,P=0.943。DCR国产吉非替尼组19外显子Del的为91.3%,原研药组为95.8%,χ~2=0.001,P=0.970。RR国产吉非替尼组21(L858R)点突变的为41.7%,原研药组为45.5%,χ~2=0.034,P=0.885;DCR国产吉非替尼组21(L858R)点突变的为66.7%,原研药组为81.8%,差异无统计学意义,χ~2=0.683,P=0.408。2组患者中19外显子Del的RR为80.9%,21(L858R)点突变的为43.5%,χ~2=10.009,P=0.002;19外显子Del的DCR为93.6%,21(L858R)点突变的为73.9%,χ~2=5.351,P=0.021。2组患者中19外显子Del的中位PFS为11.7个月,21(L858R)点突变的为8.6个月,差异有统计学意义,χ~2=10.798,P=0.001。2组主要的毒副作用是腹泻和皮疹,多为Ⅰ~Ⅱ度,差异无统计学意义,P>0.05。结论国产吉非替尼与原研药治疗EGFR敏感突变的晚期NSCLC疗效及不良反应相当,19外显子Del的患者较21(L858R)点突变的患者疗效更佳。     

Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma

Objective

The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.

Patients and methods

One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy.

Results

The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001).

Conclusions

Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.     

肺腺癌患者EGFR和KRAS基因突变与预后的相关性研究

目的 探讨肺腺癌患者表皮生长因子受体(EGFR)和KRAS基因突变与预后的相关性.方法 选取134例肺腺癌患者的肺腺癌组织标本,应用探针扩增阻滞突变系统在PCR仪上进行EGFR和KRAS基因突变检测,分析EGFR和KRAS基因突变与肺腺癌患者临床病理特征及预后的关系.结果 134例患者中,EGFR基因突变53例,突变率为39.55%,KRAS基因突变6例,突变率为4.48%.肺腺癌患者EGFR基因突变率与年龄、吸烟史有关(P﹤0.01).EGFR基因突变型患者的KRAS基因突变率低于EGFR基因野生型患者(P﹤0.05).EGFR基因突变型患者的无进展生存期(PFS)长于EGFR基因野生型患者(P﹤0.05),KRAS基因野生型患者的PFS长于KRAS基因突变型患者(P﹤0.05).结论 EGFR基因突变的肺腺癌患者KRAS基因更倾向于野生型,EGFR基因突变型或KRAS基因野生型的肺腺癌患者PFS更长.     

不同化疗方案治疗EGFR常见突变肺腺癌疗效的回顾性研究

目的:探究EGFR常见突变的肺腺癌患者最佳化疗方案。方法:回顾性收集2007年6月至2014年6月于广东省肺癌研究所就诊的晚期原发性肺腺癌患者的临床资料,分析不同化疗方案对于携带EGFR常见突变肺癌患者的疗效。结果:205例携带EGFR常见突变的肺腺癌患者纳入研究,接受吉西他滨+铂类、培美曲塞+铂类和紫杉醇类+铂类方案治疗的患者分别为119、60和26例,客观缓解率及无进展生存期分别为25.2%、25.0%、30.8%及5.5、5.2、6.2个月,差异均无统计学意义(P=0.979;P=0.811)。结论:以吉西他滨、培美曲塞和紫杉醇类为基础的含铂化疗方案在携带EGFR常见突变肺腺癌患者中的疗效并无差异。     

肺腺癌患者新鲜细胞学标本EGFR基因突变检测及意义

目的：研究采用新鲜细胞学标本检测肺腺癌患者表皮生长因子受体（EGFR）基因突变情况,用于辅助判断阳性患者服用酪氨酸激酶抑制剂（TKI）的预后。方法：收集河北医科大学第四医院癌检中心的肺腺癌患者淋巴结针吸标本和胸腔积液标本313例,经HE染色、免疫细胞化学染色后由两位细胞病理医师确诊为肺腺癌后,采用ARMS法进行EGFR基因外显子18~21突变的检测,观察突变情况;对比EGFR基因突变阳性患者采用口服TKI药物靶向治疗或化疗的客观有效率（ORR）和无进展生存期（PFS）。结果：313例标本中确诊为肺腺癌293例,其中288例提取DNA成功并得到检测,提取成功率为98.1%（288/293）,检测出130例突变,突变率为45.1%。肺腺癌患者的EGFR突变主要发生在女性、不吸烟患者中,与年龄无明显相关。EGFR基因外显子18~21突变阳性患者靶向治疗组和化疗组之间的ORR差异有统计学意义（P < 0.01）,靶向治疗组的疗效和生存期都优于化疗组。新鲜细胞学标本检测的EGFR基因突变结果以及所测阳性患者的预后与以往文献均一致。结论：新鲜细胞学标本检测的EGFR突变结果准确,可以作为肿瘤组织的代替标本。     

Carcinoembryonic antigen-related cell adhesion molecules as surrogate markers for EGFR inhibitor sensitivity in human lung adenocarcinoma

Background:

Lung adenocarcinoma (LADCA) patients with epidermal growth factor receptor (EGFR) mutations are in general associated with relatively high clinical response rate to EGFR-tyrosine kinase inhibitors (TKIs) but not all responded to TKI. It has therefore become important to identify the additional surrogate markers regarding EGFR-TKI sensitivity.

Methods:

We first examined the effects of EGFR-TKIs, gefitinib and erlotinib, upon cell proliferation of lung adenocarcinoma cell lines. We then evaluated the gene profiles related to EGFR-TKI sensitivity using a microarray analysis. Results of microarray analysis led us to focus on carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family, CEACAM 3, 5, 6, 7, and 19, as potential further surrogate markers of EGFR-TKI sensitivity. We then examined the correlation between the status of CEACAM 3, 5, 6, 7, and 19 immunoreactivity in LADCA and clinicopathological parameters of individual cases.

Results:

In the cases with EGFR mutations, the status of all CEACAMs examined was significantly higher than that in EGFR wild-type patients, but there were no significant differences in the status of CEACAMs between TKI responder and nonresponder among 22 patients who received gefitinib therapy. However, among 115 EGFR mutation-negative LADCA patients, both CEACAM6 and CEACAM3 were significantly associated with adverse clinical outcome (CEACAM6) and better clinical outcome (CEACAM3).

Conclusion:

CEACAMs examined in this study could be related to the presence of EGFR mutation in adenocarcinoma cells but not represent the effective surrogate marker of EGFR-TKI in LADCA patients. However, immunohistochemical evaluation of CEACAM3/6 in LADCA patients could provide important information on their clinical outcome.