伴有EGFR突变的非小细胞肺癌血清CYFRA21-1和CEA水平与EGFR-TKIs的疗效关系

背景与目的表皮生长因子受体-酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs）是EGFR基因突变晚期非小细胞癌（non-small cell lung cancer, NSCLC）患者一线标准治疗方案，但是临床实践中，疗效差异较大。本项实验拟研究治疗前血清细胞角蛋白19片段（cytokeratin-19 frag-ments, CYFAR21-1）和癌胚抗原（carcinoembryonic antigen, CEA）的水平是否与EGFR-TKIs疗效有关。方法回顾性分析194例EGFR基因突变阳性且接受EGFR-TKIs治疗的NSCLC患者的治疗前的血清CYFAR21-1和CEA水平与EGFR-TKIs疗效及生存时间的关系。结果血清水平CYFAR21-1增高和正常的无进展生存时间（progression-free survival, PFS）分别为7.0个月和11.9个月（P<0.001）；总生存（overall survival, OS）分别为12.6个月和28.0个月（P<0.001）。腺癌中，血清水平增高和正常的PFS分别为7.0个月和12.0个月（P<0.001），OS分别为13.1个月和28.1个月（P<0.001）。鳞癌中，血清CYFRA21-1水平高低与生存时间无关。治疗前血清CEA水平高低与生存时间无关。结论在EGFR突变肺腺癌患者，治疗前血清水平CYFAR21-1增高组EGFR-TKIs治疗的PFS和OS均较正常组短。EGFR突变肺腺癌患者，治疗前血清CYFAR21-1水平可以作为预测EGFR-TKIs治疗的疗效指标。     

107例KRAS突变阳性非小细胞肺癌患者临床分析

背景与目的鼠类肉瘤病毒癌基因（Kirsten rat sarcoma viral oncogene,KRAS）是非小细胞肺癌（non-small cell lung cancer, NSCLC）的重要驱动基因之一,研究显示KARS是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）药物的耐药标志,但其对于化疗敏感性及预后方面的意义存在争议。本研究旨在积累KRAS突变阳性的NSCLC患者治疗经验。方法我们回顾性分析了107例KRAS突变阳性的NSCLC患者的临床资料,分析KRAS突变阳性的NSCLC患者一线化疗疗效以及靶向治疗疗效。结果52例接受一线化疗的晚期KARS突变阳性NSCLC患者客观缓解率（objective response rate, ORR）为9.6%,疾病控制率（disease control rate, DCR）为53.8%,中位疾病无进展生存期（progression-free survival, PFS）为3个月;21例接受EGFR-TKIs药物治疗的KRAS突变阳性NSCLC患者ORR为9.5%,DCR为23.8%,PFS为1个月,其中EGFR/KRAS共突变患者接受EGFR-TKIs治疗的ORR及DCR均要显著高于单纯KRAS突变人群（50%vs 0,P=0.029;75%vs11.8%, P=0.043）,EGFR/KARS共突变患者接受EGFR-TKIs治疗的PFS较单纯KARS突变患者延长,可见统计学差异（3个月vs 1个月,P=0.004）。结论KRAS突变阳性NSCLC患者化疗有效率低,缓解时间短,EGFR-TKIs治疗效果差,亟需研发新的药物;EGFR/KARS共突变现象客观存在,EGFR-TKIs药物可作为这类患者有效的治疗选择之一。     

术后淋巴细胞数与单核细胞数的比值对合并高血压的肺癌患者手术预后的预测价值

目的 探讨术后淋巴细胞数与单核细胞数的比值（lymphocyte-to-monocyte ratio,LMR）对接受全麻手术的合并高血压的肺癌患者预后的预测价值。方法 回顾性分析2014年1月至2019年12月在新乡市中心医院进行肺癌全麻手术治疗的高血压患者的临床资料。采用术后LMR值预测患者手术预后的ROC曲线获得LMR的最佳截断值2.14。根据患者术后LMR分为高LMR组（≥2.14,n=67）和低LMR组（<2.14,n=148）。比较患者的临床资料。应用Kaplan-Meier法绘制生存曲线。Logrank检验比较组间总生存（overall survival,OS）和无进展生存（progression-free survival,PFS）差异。应用Cox风险回归模型单因素及多因素分析筛选影响合并高血压的肺癌患者全麻手术生存预后的独立危险因素。结果 多因素分析显示，肿瘤TNM分期、术后LMR和术中出血量均是合并高血压的肺癌患者OS和PFS的独立影响因素（均P<0.05）。低LMR组患者3年和5年OS率分别为68.8%和45.4%，而高LMR组分别为86.0%和71.3...     

外周血炎症指标与非小细胞肺癌EGFR突变的相关性

目的:研究非小细胞肺癌（non-small cell lung cancer,NSCLC）患者表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变与中性粒细胞与淋巴细胞比值（NLR）、淋巴细胞与单核细胞比值（LMR）、系统性炎症反应指数（SIRI）三种炎性指标及患者临床病理学特征的相关性。方法:通过回顾性分析的方法比较136例非小细胞肺癌患者EGFR突变型与野生型在各项临床指标、外周血三种免疫细胞及炎症指标上的差异。结果:EGFR野生型患者与突变型患者在性别、吸烟史、病理类型上比较,差异有统计学意义（P＜0.05）。EGFR突变型相较于野生型以未吸烟、女性患者、腺癌患者居多。EGFR野生型与突变型在NLR、LMR、SIRI上差异有统计学意义（P＜0.05）。EGFR突变型患者治疗前LMR高于野生型患者,EGFR突变型患者治疗前NLR和SIRI低于野生型患者。结论:炎症指标LMR、NLR、SIRI与NSCLC患者EGFR突变具有相关性。LMR对EGFR突变有一定的预测价值,且优于SIRI与NLR。     

治疗前外周血炎性标志物对EGFR突变阳性晚期非小细胞肺癌患者的预后价值研究

  目的  探讨治疗前外周血炎性标志物在表皮生长因子受体（epidermal growth factor receptor,EGFR）阳性晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者中的预后作用。  方法  回顾性分析2015年1月至2018年10月中国人民解放军总医院第五医学中心142例EGFR突变阳性晚期NSCLC患者临床资料。通过受试者工作特征曲线（receiver operating characteristic curve,ROC）确定中性粒细胞与淋巴细胞计数比值（neutrophil-to-lymphocyte ratio,NLR）、血小板与淋巴细胞计数比值（platelet-to-lymphocyte ratio,PLR）、系统免疫炎症指数（systemic immune-inflammation index,SII）和淋巴细胞与单核细胞计数比值（lymphocyte-to-monocyte ratio,LMR）的最佳临界值,应用Kaplan-Meier方法进行生存分析。Cox比例风险模型评估各变量的预测价值。  结果  NLR、PLR、SII和LMR的最佳临界值分别为2.60、167.32、687.39和3.13。根据最佳临界值分别将研究对象分为高值组和低值组,高NLR、PLR和SII组的中位无进展生存期（median progression-free survival,mPFS）及中位总生存期（median overall survival,mOS）均显著低于低值组中相应值,高LMR组mPFS及mOS较低LMR组延长。  结论  治疗前升高的NLR、PLR、SII和降低的LMR可能与接受靶向治疗的EGFR突变阳性晚期NSCLC患者的不良预后相关。      

EGFR基因突变型与野生型非小细胞肺癌脑转移预后的病例对照研究

目的：探讨表皮生长因子受体（epidermal growth factor receptor,EGFR）基因突变与非小细胞肺癌（non-small cell lung cancer,NSCLC）伴脑转移患者预后的相关性,为改善NSCLC合并脑转移患者预后、指导个体化治疗提供临床依据。方法：回顾性分析福建省立医院2013年1月1日至2018年9月30日期间收治的88例NSCLC合并脑转移患者的临床资料,随访取得患者的死亡时间,随访截止日期为2019年10月31日。收集和分析的临床资料包括性别、年龄、吸烟史、病理类型、基因检测、治疗情况、无进展生存期（progression free survival,PFS）、总生存期（overall survival,OS）等。运用生存分析（Kaplan-Meier生存时间曲线）评价EGFR突变型患者的预后,以单因素分析（log-rank检验）预测影响EGFR-TKI治疗效果的因素。结果：88例NSCLC脑转移患者有57例为EGFR突变型,其中位PFS（MPFS）为13.0个月（95%CI：11.951~14.049）,明显高于EGFR野生型患者（P=0.003）,患者中位生存期（median survival time,MST）为29.0个月（95%CI：20.531~37.468）,明显高于EGFR野生型（P=0.001）。EGFR突变型中,Exon19-del突变组患者较Exon21 L858R突变组患者OS有延长趋势（P=0.05）,Exon19-del+Exon20T790M突变组患者OS较Exon21 L858R突变组有延长趋势（P=0.077）。结论：EGFR突变组较野生型组NSCLC脑转移患者预后相对好些,且携带19外显子单一缺失突变的患者预后最好。     

NLR、dNLR、PLR对195例广泛期小细胞肺癌预后评估价值分析

摘 要：［目的］ 探讨广泛期小细胞肺癌（small cell lung cancer）患者中性粒细胞/淋巴细胞比值（neutrophil-to-lymphocyte ratio，NLR）、血小板/淋巴细胞比值(platelet-to-lymphocyte ratio，PLR)、衍生中性粒细胞/淋巴细胞比值(derive neutrophil-to-lymphocyte ratio，dNLR)对预后的评估价值。［方法］ 选取195例广泛期SCLC患者，收集患者血常规数据，分析临床特征、NLR、dNLR、PLR对预后的影响。根据ROC曲线得到NLR、dNLR、PLR的最佳临界值，分析NLR、dNLR、PLR对广泛期SCLC患者PFS和OS的影响。［结果］ ROC曲线得到NLR、dNLR、PLR最佳临界值分别为2.4、2.2和170。单因素分析显示EP/C方案化疗＞4个周期、放疗、NLR≤2.4、dNLR≤2.2、PLR≤170与较长中位无进展生存期（progression-free survival，PFS）相关（P＜0.05），年龄≤60岁、女性、EP/C方案化疗＞4个周期、放疗、NLR≤2.4、dNLR≤2.2、PLR≤170与较长总生存期（overall survival，OS）相关。Cox回归分析显示放疗（HR=0.29，95%CI：0.20～0.42，P＜0.01）、EP/C方案化疗＞4个周期（HR=0.56，95%CI：0.39～0.79，P＜0.01）有利于PFS延长，NLR＞2.4（HR=1.64，95%CI：1.08～2.50，P=0.02）为PFS的危险因素；放疗（HR=0.24，95%CI：0.17～0.36，P＜0.01）、EP/C方案化疗＞4个周期（HR=0.64，95%CI：0.45～0.91，P=0.01）有利于OS延长，年龄＞60岁（HR=1.66，95%CI：1.16～2.36，P＜0.01）、NLR＞2.4（HR=2.60，95%CI：1.65～4.09，P＜0.01）、dNLR＞2.2（HR=1.651，95%CI：1.11～2.47，P=0.01）为OS的危险因素。［结论］ NLR、dNLR、PLR与广泛期SCLC患者预后相关，高NLR患者PFS较短，高NLR、高dNLR患者OS较短。     

外周血NLR和PLR评估晚期非小细胞肺癌一线含铂双药化疗疗效和预后的价值

目的:探讨化疗前外周血NLR和PLR与晚期NSCLC患者接受一线含铂双药化疗疗效和预后的相关性。方法:选取在我院确诊的初治晚期NSCLC患者230例,计算化疗前NLR和PLR,并根据ROC曲线图计算其截断值。分析NLR和PLR与NSCLC临床病理特征的关系。分别比较各组患者中位生存时间的差异;采用单因素及多因素 Logistic 回归对预后因素进行分析。结果:根据ROC曲线计算NLR和 PLR临界值分别为:4.5和235。外周血PLR与治疗反应显著相关（P<0.05）,而NLR与治疗反应无明显相关（P>0.05）。高NLR组和低NLR组OS分别为:11个月和15.8个月（P<0.001）;高PLR组和低PLR组OS分别为:12个月和15.2个月（P<0.001）。单因素和多因素结果显示,NLR和PLR是晚期NSCLC预后的独立影响因素。结论:外周血PLR一定程度上可预测化疗反应,NLR和PLR是晚期NSCLC预后的独立影响因素,治疗前评估NLR和PLR可以判断晚期NSCLC患者的预后。     

术前NLR、PLR在非小细胞肺癌患者预后中的价值

目的：评估术前中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio, NLR）、血小板/淋巴细胞比值（platelet to lymphocyte ratio, PLR）在非小细胞肺癌（non-small cell lung cancer, NSCLC）患者预后中的价值。方法：回顾性分析2012年1月至2014年4月四川省肿瘤医院行根治性手术治疗的280例NSCLC患者的临床病理资料，根据受试者工作特征曲线（receiver operating characteristic curve, ROC）确定NLR、PLR的临界值，分析NLR、PLR与患者预后的相关性。结果：选取NLR=3.25和PLR=122作为临界值。单因素分析显示TNM分期、T分期、N分期与无病生存期（disease-free survival, DFS）相关，P值分别为0.001、0.007、＜0.001；年龄、TNM分期、T分期、N分期、PLR与总生存期（overall survival, OS）相关，P值分别为0.006、＜0.001、0.035、＜0.001、＜0.001。多因素分析显示TNM分期（HR：1.627 ,95% CI：1.030-2.568，P=0.037）是影响DFS的独立危险因素。年龄（HR：1.785，95% CI：1.216-2.622，P = 0.003）、TNM分期（HR：2.094，95% CI：1.231-3.560，P = 0.006）、PLR（HR：1.833，95% CI：1.257-2.674，P = 0.002）是影响OS的独立危险因素。结论：PLR可作为评估经根治性手术治疗NSCLC患者预后的参考指标。     

淋巴细胞与单核细胞比值对晚期肺癌预后预测的价值

目的:探讨淋巴细胞与单核细胞比值（LMR）对晚期肺癌预后预测的价值。方法:回顾性分析2012年12月至2014年12月初次就诊我院的晚期肺癌患者，LMR分界值由受试者工作曲线（ROC）分析确定；分析LMR表达与晚期肺癌患者临床特征的关系；采用Cox风险回归模型分析影响晚期肺癌患者总生存的预后因素。结果:根据ROC曲线，LMR最佳临界值AUC=0.581，所有研究对象分为高LMR（n=34）和低LMR（n=13）。LMR水平与病理类型、临床分期、ECOG评分有关（P<0.05）；与年龄、性别、吸烟史无关（P>0.05）。高LMR组和低LMR组的中位OS分别为28.8个月和16.2个月；中位PFS时间分别20.7个月和11.6个月，两组比较均有统计学差异（P<0.05）；Cox风险比例模型显示病理类型、吸烟史和LMR水平是影响晚期肺癌患者总生存的独立预后因素（P<0.05）。结论:LMR是晚期肺癌患者预后的独立影响因素之一，且与晚期肺癌的生存呈正比关系，对晚期肺癌患者的预后具有良好的预测价值。     

淋巴细胞相关炎性反应指标与乳腺癌预后的相关性

目的 探讨治疗前中性粒细胞淋巴细胞比（NLR）、淋巴细胞单核细胞比（LMR）、血小板淋巴细胞比（PLR）与乳腺癌患者临床病理特征及预后的关系。 方法 回顾性分析189例乳腺癌患者的临床资料,应用ROC曲线获得NLR、LMR、PLR的临界值。根据临界值将患者分为高低两组,分析NLR、LMR、PLR与临床病理特征及预后的相关性。结果 NLR、LMR、PLR最佳临界值分别为2.4、5.4、113。高低NLR组患者的新辅助化疗和手术治疗差异有统计学意义（均P<0.05）,高低LMR组和PLR组患者在各临床病理特征方面差异无统计学意义（均P>0.05）。单因素分析结果显示,TNM临床分期、PR表达、NLR、LMR、PLR、手术以及内分泌治疗均与OS有关（均P<0.05）;TNM临床分期、HER2表达、NLR、手术以及内分泌治疗均与PFS有关（均P<0.05）。多因素分析结果显示,TNM临床分期（P=0.003）和NLR（P=0.033）是OS的独立危险因素;TNM临床分期（P=0.002）和手术治疗（P=0.040）是PFS的独立影响因素。结论 治疗前NLR、LMR、PLR与乳腺癌的预后存在显著相关性,但仅NLR是独立危险因素,LMR、PLR尚不能作为独立预测因子。     

Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: A meta-analysis from six phase III randomized controlled trials

Gefiinib and erlotinib are two similar small molecules of selective and reversible epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), which have been approved for second-line or third-line indication in previously treated advanced Non-small-cell lung cancer (NSCLC) patients. The results of comparing the EGFR-TKI with standard platinum-based doublet chemotherapy as the first-line treatment in advanced NSCLC patients with activated EGFR mutation were still controversial. A meta-analysis was performed to derive a more precise estimation of these regimens. Finally, six eligible trials involved 1,021 patients were identified. The patients receiving EGFR-TKI as front-line therapy had a significantly longer progression-free survival (PFS) than patients treated with chemotherapy [median PFS was 9.5 versus 5.9 months; hazard ratio (HR)=0.37; 95% confidence intervals (CI)=0.27-0.52; p<0.001]. The overall response rate (ORR) of EGFR-TKI was 66.60%, whereas the ORR of chemotherapy regimen was 30.62%, which was also a statistically significant favor for EGFR-TKI [relative risk (RR)=5.68; 95% CI=3.17-10.18; p<0.001]. The overall survival (OS) was numerically longer in the patients received EGFR-TKI than patients treated by chemotherapy, although the difference did not reach a statistical significance (median OS was 30.5 vs. 23.6 months; HR=0.94; 95% CI=0.77-1.15; p=0.57). Comparing with first-line chemotherapy, treatment of EGFR-TKI achieved a statistical significantly longer PFS, higher ORR and numerically longer OS in the advanced NSCLC patients harboring activated EGFR mutations, thus, it should be the first choice in the previously untreated NSCLC patients with activated EGFR mutation.     

EGFR-TKIs联合化疗一线治疗晚期EGFR基因突变非小细胞肺癌患者的疗效观察

目的:分析比较表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)联合化疗与EGFR-TKIs单药一线治疗晚期非小细胞肺癌(NSCLC)的疗效和安全性。方法:回顾性分析2010年09月至2015年12月晚期EGFR突变阳性NSCLC患者100例,根据治疗方案分为联合组(50例)和单药组(50例),联合组采用EGFR-TKIs联合化疗治疗,单药组采用EGFR-TKIs单药治疗。比较两组患者的治疗效果、预后情况以及毒副作用。结果:联合组总有效率为66%(33/50),单药组为48%(24/50),组间比较差异无统计学意义(P=0.106);联合组的疾病控制率为88%(44/50),单药组的疾病控制率为68%(34/50),组间比较差异有统计学意义(P=0.028)。联合组和单药组的中位PFS分别为18.5个月和13.5个月,差异有统计学意义(P=0.013),两组的OS分别为36个月和28.5个月,差异无统计学意义(P=0.071)。单药组和联合组的3-4级治疗相关不良反应发生率分别为6%和10%,差异无统计学意义(P=0.463)。结论:与EGFR-TKIs单药相比,EGFR-TKIs...     

Systemic Inflammatory Markers of Survival in Epidermal Growth Factor–Mutated Non–Small-Cell Lung Cancer: Single-Institution Analysis,Systematic Review,and Meta-analysis

BackgroundSystemic inflammatory response (SIR) may influence prognosis in epidermal growth factor receptor (EGFR)-mutated (m) non–small-cell lung cancer (NSCLC). Pretreatment SIR markers (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio [LMR], lactate dehydrogenase [LDH], and lung immune prognostic index [LIPI]) were assessed as prognostic factors in NSCLC survival.Patients and MethodsRetrospective survival analysis (overall survival [OS] and progression-free survival [PFS]) of EGFR-mutated NSCLC patients at Princess Margaret Cancer Centre were performed separately for early (I-IIIa) and late (IIIb-IV) stage disease for individual SIR variables, dichotomized by optimal cutoff points by Kaplan-Meier survival analysis and multivariable Cox proportional hazard modeling. A systematic review and meta-analysis of known SIR studies in patients with late-stage EGFR-mutated were also performed.ResultsFrom 2012 to 2019, in 530 patients, significant adjusted hazard ratios (aHR) for OS comparing high versus low NLR were 2.12 for early stage and 1.79 for late stage disease. Additionally, late stage cohorts had significant associations, as follows: high versus low derived NLR, aHR = 1.53; LMR, aHR = 0.62; LDH, aHR = 2.04; and LIPI, aHR = 2.04. Similar patterns were found for PFS in early stage NLR (aHR = 1.96) and late stage NLR (aHR = 1.46), while for PFS, only late stage derived NLR (aHR = 1.34), LDH (aHR = 1.75), and LIPI (aHR = 1.66) were significant. A meta-analysis confirmed that NLR, LMR, LDH, and LIPI were all significantly associated with OS and PFS in the late stage.ConclusionThis primary study and meta-analysis demonstrated that LMR and LDH were significantly associated with late stage EGFR-mutated NSCLC outcomes, and the LIPI scoring system was prognostic. NLR remained an independent prognostic factor across all stages and could represent an early marker of immuno-oncology interactions.     

Expression of insulin-like growth factor 1 receptor (IGF-1R) predicts poor responses to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in non-small cell lung cancer patients harboring activating EGFR mutations

ObjectivesExpression of insulin-like growth factor 1 receptor (IGF-1R) in non-small cell lung cancer (NSCLC) is associated with poor prognosis. The IGF-1R pathway activates downstream targets that bypass dependency in signals from the epidermal growth factor receptor (EGFR), which mediates resistance to EGFR tyrosine kinase inhibitors (TKIs). The aim of the present study was to determine the predictive role of IGF-1R expression in the response to EGFR-TKIs of NSCLC patients harboring activating EGFR mutations.Materials and methodsWe retrospectively studied 62 NSCLC patients who had activating EGFR mutations and received TKIs. Protein expression of IGF-1R, vascular endothelial growth factor (VEGF), and human epidermal growth factor receptor 2 (HER2) were measured by immunohistochemical staining. Univariate and multivariate analyses were performed to identify predictive factors associated with the responses to EGFR-TKIs. The relationship of progression-free survival (PFS) with IGF-1R expression and the presence of diabetes mellitus (DM) were examined.ResultsOf 62 EGFR mutation positive patients, 26 expressed IGF-1R, and 13 had DM. In the multivariate analysis, young age, squamous cell carcinoma, and IGF-1R expression were independently associated with a shorter PFS after treatment with EGFR-TKIs. Patients expressing IGF-1R showed a significantly shorter PFS in response to EGFR-TKIs compared with those lacking IGF-1R expression (9.1 vs. 20.1 months, p = 0.005). The 13 patients with DM were more likely to express IGF-1R (p = 0.001) and had shorter PFS times when treated with first-line EGFR-TKIs (7.6 vs. 18.6 months, p = 0.005), compared with those without DM.ConclusionIGF-1R expression was a negative predictive factor for a response to EGFR-TKIs in NSCLC patients harboring activating EGFR mutations. Moreover, patients with DM highly expressed IGF-1R in tumor tissues, which was associated with a poor response to first-line TKI therapy. Further studies aimed at overcoming EGFR-TKI resistance will need to also address IGF-1R pathways.     

Uncommon single and compound EGFR mutations: clinical outcomes of a heterogeneous subgroup of NSCLC

Molecular characterization of non-small-cell lung cancer (NSCLC) is essential to define the correct therapeutic algorithm in metastatic disease. Approximately 90% of epidermal growth factor receptor (EGFR) mutations are usually associated with sensitivity to EGFR tyrosine kinase inhibitors (TKIs). The remaining 10% defines a small, extremely heterogeneous subgroup of mutations, with a varied profile of sensitivity and response to target therapies.This retrospective observational study includes 47 patients affected by metastatic NSCLC harboring uncommon EGFR mutations (single or compound mutation). Patients were treated with EGFR-targeting TKIs or platinum-based chemotherapy as first-line treatment.Median OS resulted longer in the compound mutation group when compared to single rare mutations (33.6 vs 12 months; P = 0.473); a similar result was observed for PFS (16 vs 7.6 months; P = 0.281), although statistical significance was not reached. ORR, PFS and OS resulted similar for patients treated with first-line EGFR TKIs or chemotherapy. No difference in terms of PFS and OS was found according to the TKI administered.Compound mutations seem to be a good prognostic indicator for OS; they are also predictive of response to 1st and 2nd generation EGFR TKIs, as well as exon 19 insertions and mutations in codon 719 of exon 18. For mutations in exon 18 (not in codon 719) and exon 20 insertions, chemotherapy seems the most effective available option. The addition of immunotherapy to chemotherapy could change this approach in the next future.     

EGFR mutation: Significance as a stratification factor in the era of molecular-targeted therapy

Somatic mutations of epidermal growth factor receptor (EGFR) are the strongest predictive markers for the response to EGFR-tyrosine kinase inhibitors (TKIs). Patients with EGFR mutations generally receive EGFR-TKI treatment, and their survival has been significantly improved compared with that before the development of EGFR-TKIs. This study aimed to clarify the impact of EGFR mutational status on the survival of patients with non-small cell lung cancer (NSCLC) receiving cytotoxic agents, but not EGFR-TKIs, as their first-line chemotherapy. In addition, we analyzed patients with EGFR mutations to determine whether the timing of EGFR-TKI administration affects overall survival (OS). A total of 83 NSCLC patients with stage IIIB/IV who received chemotherapy alone and whose EGFR mutational status was known were investigated. Univariate and multivariate analysis for OS was performed using parameters such as age, gender, performance status (PS), histology, disease stage, smoking status, EGFR mutational status and administration of a first-line regimen. Among the 52 patients with EGFR mutations who received EGFR-TKIs, OS between those who received EGFR-TKIs as their first-line treatment and after chemotherapy were similar. Among the 83 patients who received cytotoxic agents as their first-line chemotherapy, the multivariate analysis showed OS to be significantly associated with PS (p<0.001), histology (p=0.039) and EGFR mutational status (p=0.040). OS was almost similar among the 52 patients with EGFR mutations who received EGFR-TKIs in a first- and second-line setting (25.6 vs. 26.8 months, p=0.914). The EGFR mutational status had a significant impact on the survival of NSCLC patients, although these patients did not receive EGFR-TKIs as their first-line chemotherapy. In future randomized trials, even when EGFR-TKIs are not included in experimental regimens, patients may need to be stratified by EGFR mutational status in order that study results be evaluated appropriately.     

对比EGFR-TKIs治疗EGFR突变状态未明晚期NSCLC疗效研究

目的探讨对比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)一线、维持及二线治疗EGFR突变状态未明晚期非小细胞肺癌(non-small-cell lung cancer,NSCLC)的疗效。方法回顾性分析接受EGFR-TKIs治疗的57例EGFR突变状态未明晚期NSCLC,按照接受EGFR-TKIs治疗的时机分为EGFR-TKIs治疗一线组(19例)、维持组(18例)和二线组(20例),按照RECIST标准进行疗效评价。结果一线组、维持组和二线组客观有效率(52.6%vs 38.9%vs 35.0%,P=0.098)、中位无进展生存期(4.0月vs 7.8月vs 2.2月,P=0.417)差异无统计学意义,但一线组患者总生存期较维持组和二线组差(8.7月vs 20.0月vs 19.1月,P=0.009)。结论 EGFR突变状态未明晚期NSCLC EGFR-TKIs一线、维持和二线治疗的客观有效率和中位无进展生存期相似,但EGFR-TKIs一线治疗总生存期较短,建议EGFR-TKIs用于维持或二线治疗EGFR突变状态未明晚期NSCLC。