BRCA1表达与吉非替尼治疗EGFR基因突变型晚期非小细胞肺癌疗效的关系

目的：探讨BRCA1表达与吉非替尼治疗EGFR突变型晚期非小细胞肺癌患者的疗效关系。方法：纳入我院2013年1月至2014年11月确诊为EGFR突变型晚期非小细胞肺癌的患者50例,口服吉非替尼进行治疗,直至疾病进展或者出现不可耐受的毒副反应,采用免疫组织化学方法检测EGFR突变型晚期非小细胞肺癌患者中BRCA1的表达情况,并通过收集的临床资料回顾性分析吉非替尼对EGFR突变型晚期非小细胞肺癌病人的治疗效果。结果：BRCA1高表达率为36.00%(18/50),BRCA1高表达组吉非替尼有效率为33.33%(6/18),BRCA1低表达组吉非替尼有效率为68.75%(22/32),两者差异有统计学意义(P＜0.05)。结论：吉非替尼治疗EGFR突变型晚期非小细胞肺癌患者中,BRCA1低表达患者受益比高表达患者明显,BRCA1可以作为吉非替尼治疗EGFR突变型晚期非小细胞肺癌的预测因素。     

KRAS和表皮生长因子受体突变基因与原发性非小细胞肺癌的相关性

目的 研究KRAS和表皮生长因子受体(EGFR)基因在原发性非小细胞肺癌(NSCLC)中的突变状态以及其与靶向治疗效果的相关性。方法 收集郑州大学第一附属医院收治的150例经病理证实的NSCLC患者原发肿瘤及受累的淋巴结标本,进行KRAS和EGFR突变基因序列分析。150例中12例患者纵隔淋巴结转移灶经DNA序列分析发现EGFR基因突变后给予吉非替尼进行术前辅助治疗。结果150对（分别为原发灶和受累淋巴结）标本中,2例原发肿瘤和10例淋巴结转移灶中检测到KRAS突变基因,35例原发肿瘤和44例淋巴结转移灶中检测到EGFR突变基因。KRAS和EGFR基因在原发灶和转移灶中不一致的比率分别为6.7％ (10/150)和8.7％ (13/150)。1例原发肿瘤无EGFR突变的患者接受吉非替尼治疗后效果不佳。结论 NSCLC患者原发灶和转移灶中KRAS和EGFR基因突变状态不一致,这对于应用酪氨酸激酶抑制剂靶向治疗NSCLC具有重要的参考意义。     

一代EGFR-TKIs治疗后进展的晚期NSCLC外周血T790M突变特征

目的探究真实世界中表皮生长因子受体(EGFR)敏感突变的晚期NSCLC患者使用吉非替尼、厄洛替尼、埃克替尼一线治疗进展后T790M突变的分布特征。 方法2017年6月至2019年6月期间557例肺癌患者,145例经病理组织学或细胞学确诊为晚期非小细胞肺癌(NSCLC)且具有EGFR敏感突变的患者,给予吉非替尼、厄洛替尼、埃克替尼一线治疗。随访进展后,采集其外周血10 ml,利用Super-ARMS法检测T790M突变。通过χ²检验,Kaplan-Meier分析,回顾性分析晚期NSCLC患者接受吉非替尼、厄洛替尼、埃克替尼一线治疗后T790M突变患者的分布特征。 结果回顾性分析的145例患者,56例一线接受吉非替尼治疗,16例接受厄洛替尼治疗,73例接受埃克替尼治疗。Super-ARMS检测结果显示,一代EGFR-TKIs治疗进展后T790M突变的总体发生率为40% (58/145),其中吉非替尼组41.07% (23/56)、厄洛替尼组31.25%(5/16)、埃克替尼组41.10% (30/73)。三组患者之间T790M突变的发生率无统计学差异。但是,肺腺癌(P＝0.0001)及初始EGFR突变为19del(P＝0.0014)的患者更易发生T790M突变。T790M阳性患者中,吉非替尼、厄洛替尼、埃克替尼的中位PFS(mPFS)分别为：11个月、18个月和12个月,组间无统计学差异。TKI治疗1年、2年后T790M突变率及T790M阳性人群的中位PFS均无统计学差异。 结论真实世界中吉非替尼、厄洛替尼、埃克替尼一线治疗晚期NSCLC耐药进展后,其血检标本T790M的突变发生率无统计学差异。但是,初始突变为19del的患者相较于L858R突变的患者更容易发生T790M突变。这也进一步预示着NSCLC患者精细化管理的必要性。     

EGFR mutations and HER2/3 protein expression and clinical outcome in Chinese advanced non-small cell lung cancer patients treated with gefitinib

Background  To assess the role of various epidermal growth factor receptor (EGFR) mutations and HER2/3 protein expression as predictive markers of responsiveness to gefitinib therapy in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods  A total of 106 Chinese NSCLC patients who had failed at least one chemotherapy regimen received gefitinib 250 mg once daily. All the 106 tumors from these patients were screened for mutations in the EGFR exons 18–24, and 84 tumors were studied by immunohistochemistry for HER2/3 expression and correlated with clinical treatment outcome. Results  Patients with EGFR mutations had a significantly higher overall response rate (ORR), longer time to progression (TTP) and overall survival (OS) compared with those with wild-type receptor. No difference in ORR was observed between patients with exon 19 deletion and patients with other EGFR mutations. ORR in HER2-positive patients was significantly higher than in the HER2-negative group, irrespective of EGFR mutational status, and a trend for better ORR was observed for HER3-positive patients. HER2 and HER3 expression levels were not associated with any difference in terms of TTP and OS. Nevertheless, when considering the subgroups of non-responders to gefitinib, median TTP in patients with mutated EGFR was significantly longer than in those with no mutations (8.0 vs. 3.0 months, P = 0.0065). EGFR-mutated patients had no significant difference in ORR, TTP and OS according to HER2 and/or HER3 expression. Conclusions  EGFR mutations are effective predictors for gefitinib efficacy in Chinese patients with advanced NSCLC. HER2 and HER3 expression does not provide any additional information for selecting patients most likely to benefit from gefitinib treatment.     

Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer

To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P = 0.0023). Smoking status (never smoker vs. smoker, P = 0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P = 0.0011), but not EGFR amplification (P = 0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P = 0.0125), but not correlated with prognosis (P = 0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.     

Factors predicting response to EGFR tyrosine kinase inhibitors

Over the past few years, two epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib (Iressa) and erlotinib (Tarceva), have been developed for the treatment of patients with cancer. In patients with non-small cell lung cancer (NSCLC), these therapies occasionally demonstrate remarkable and durable activity. However, EGFR TKIs are active in only a small subset of patients. Responders are more often nonsmokers, of East Asian descent, and female, and have tumors with adenocarcinoma histology. In April 2004, two groups reported that a cluster of somatic mutations in the kinase domain of the EGFR are observed in the majority of NSCLCs that demonstrate remarkable responses to EGFR TKIs. These findings have been validated by other investigators and have revolutionized the manner in which clinicians are thinking about their utilization for the treatment of NSCLC. This review focuses on the clinical experience with EGFR TKIs, the present knowledge regarding the biology of EGFR mutations, the limitations of using EGFR mutational status to predict who will respond to EGFR TKIs, and the implications of this information on the use of these agents for the treatment of advanced NSCLC.     

Molecular imaging of active mutant L858R EGF receptor (EGFR) kinase-expressing nonsmall cell lung carcinomas using PET/CT

The importance of the EGF receptor (EGFR) signaling pathway in the development and progression of nonsmall cell lung carcinomas (NSCLC) is widely recognized. Gene sequencing studies revealed that a majority of tumors responding to EGFR kinase inhibitors harbor activating mutations in the EGFR kinase domain. This underscores the need for novel biomarkers and diagnostic imaging approaches to identify patients who may benefit from particular therapeutic agents and approaches with improved efficacy and safety profiles. To this goal, we developed 4-[(3-iodophenyl)amino]-7-{2-[2-{2-(2-[2-{2-([(18)F]fluoroethoxy)-ethoxy}-ethoxy]-ethoxy)-ethoxy}-ethoxy]-quinazoline-6-yl-acrylamide ([(18)F]F-PEG6-IPQA), a radiotracer with increased selectivity and irreversible binding to the active mutant L858R EGFR kinase. We show that PET with [(18)F]F-PEG6-IPQA in tumor-bearing mice discriminates H3255 NSCLC xenografts expressing L858R mutant EGFR from H441 and PC14 xenografts expressing EGFR or H1975 xenografts with L858R/T790M dual mutation in EGFR kinase domain, which confers resistance to EGFR inhibitors (i.e., gefitinib). The T790M mutation precludes the [(18)F]F-PEG6-IPQA from irreversible binding to EGFR. These results suggest that PET with [(18)F]F-PEG6-IPQA could be used for the selection of NSCLC patients for individualized therapy with small molecular inhibitors of EGFR kinase that are currently used in the clinic and have a similar structure (i.e., iressa, gefitinib, and erlotinib).     

Erlotinib as a salvage treatment after gefitinib failure for advanced non-small-cell lung cancer patients with brain metastasis: A successful case report and review

Rationale:The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib.Patient concerns:We described a 55-year-old man with good performance status (PS).Diagnoses:He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018.Interventions:He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib.Outcomes:It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable.Lessions:This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.     

ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines

Therapies that target the EGF receptor (EGFR), such as gefitinib (IRESSA), are effective in a subset of patients with advanced non-small cell lung cancer (NSCLC). The differences in intracellular signaling networks between gefitinib-sensitive and -resistant NSCLCs remain poorly understood. In this study, we observe that gefitinib reduces phospho-Akt levels only in NSCLC cell lines in which it inhibits growth. To elucidate the mechanism underlying this observation, we compared immunoprecipitates of phosphoinositide 3-kinase (PI3K) between gefitinib-sensitive and -resistant NSCLC cell lines. We observe that PI3K associates with ErbB-3 exclusively in gefitinib-sensitive NSCLC cell lines. Gefitinib dissociates this complex, thereby linking EGFR inhibition to decreased Akt activity. In contrast, gefitinib-resistant cells do not use ErbB-3 to activate the PI3K/Akt pathway. In fact, abundant ErbB-3 expression is detected only in gefitinib-sensitive NSCLC cell lines. Two gefitinib-sensitive NSCLC cell lines with endogenous distinct activating EGFR mutations (L858R and Del747-749), frequently observed in NSCLC patients who respond to gefitinib, also use ErbB-3 to couple to PI3K. Down-regulation of ErbB-3 by means of short hairpin RNA leads to decreased phospho-Akt levels in the gefitinib-sensitive NSCLC cell lines, Calu-3 (WT EGFR) and H3255 (L858R EGFR), but has no effect on Akt activation in the gefitinib-resistant cell lines, A549 and H522. We conclude that ErbB-3 is used to couple EGFR to the PI3K/Akt pathway in gefitinib-sensitive NSCLC cell lines harboring WT and mutant EGFRs.     

Impact of EGFR mutation status on tumor response and progression free survival after first-line chemotherapy in patients with advanced non-small-cell lung cancer: a meta-analysis

Objectives

Non-small-cell lung cancer (NSCLC) patients harboring sensitive epidermal growth factor receptor (EGFR) mutations derive greater benefits from EGFR-tyrosine kinase inhibitors (EGFR-TKIs) than those with wild type tumors. However, whether EGFR mutation status is associated with the efficacy of cytotoxic chemotherapy or prognosis in advanced NSCLC patients remained controversial. Thus, we sought to conduct a meta-analysis to answer this question.

Methods

Electronic databases were searched for eligible literatures. The primary outcomes were objective response rate (ORR) and 6-month progression-free survival (PFS) rate. The pooled odds ratio (OR) was calculated using random-effects model. Subgroup analyses stratified by study types, EGFR mutation detection methods, chemotherapy regimens, and patient origins were proposed.

Results

A total of 14 studies involving 1,772 advanced NSCLC patients with known EGFR mutation status who had received first-line chemotherapy were included. Patients with positive EGFR mutation had numerically higher ORR than wild type patients (36.2% vs. 30.1%) without significant differences (OR 1.24, 95% CI, 0.90 to 1.70; P=0.19). However, patients with EGFR mutants had significantly superior 6-month PFS rate than wild-type patients (58.6% vs. 47.2%; OR 1.88, 95% CI, 1.33 to 2.65; P=0.0003). Results of the subgroup analyses were concordant with the overall ones.

Conclusions

This comprehensive analysis revealed that advanced NSCLC patients with sensitivity EGFR mutation had higher 6-month PFS rate and potentially greater ORR compared with wild-type patients after first-line chemotherapy. It suggested that EGFR mutation status should be considered a significant factor for patient stratification in evaluating the efficacy of antitumor agents in addition to EGFR-TKIs.     

T790M and acquired resistance of EGFR TKI: a literature review of clinical reports

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib are promising therapies for patients with advanced non-small-cell lung cancer (NSCLC). Patients with somatic activating mutations in the EGFR gene have dramatic response initially, but would eventually develop resistance to these TKIs. Subsequent studies found that a secondary mutation in the EGFR gene (T790M mutation) and amplification of the MET proto-oncogene could be the main resistance mechanisms involved. The current review is focused on T790M, which is thought to cause steric hindrance and impair the binding of gefitinib/erlotinib. The T790M is present as a minor allele before TKI therapy and accounts for about half of the acquired resistant cases. Conflicting results were reported for gefitinib-resistant, T790M-acquired patients who had switched to erlotinib treatment, which was proposed to be efficacious. The switch therapy was presumed to work for EGFR wild type patients and previously gefitinib responding patients. MET amplification accounts for about 20% of TKI acquired-resistant patients by a different molecular pathway from T790M; some of these patients will also concurrently have T790M mutation and might still not respond to irreversible TKI. As for the detection of T790M, polymerase chain reaction (PCR), especially mutant-enriched PCR was found to be more sensitive than direct DNA sequencing. In addition, whole genome amplification might also be useful and can be incorporated with future noninvasive method for detecting T790M. A better understanding of the mechanisms leading to TKI resistance is crucial in the development of effective treatment and the design of future clinical studies.     

外周血DNA EGFR基因CA-SSR多态与晚期非小细胞肺癌吉非替尼临床疗效的关系

目的探讨外周血DNA表皮生长因子受体（EGFR）基因第1内含子区CA-SSR多态性与晚期非小细胞肺癌患者吉非替尼临床疗效的相关性。方法采用PCR扩增和序列测定的方法对60例接受过吉非替尼治疗的晚期非小细胞肺癌患者外周血DNA进行分析,确定CA-SSR多态的基因型,统计分析CA-SSR多态性与吉非替尼临床疗效的相关性。结果在60例患者中短CA重复序列的患者（至少一条等位基因CA重复数≤16）吉非替尼治疗后的临床获益率为85.7%,而长CA重复序列的患者（两条等位基因CA重复数均〉16）治疗后的临床获益率为48.7%,CA-SSR多态性与近期疗效具有显著的相关性（P〈0.05）,但两组患者的无进展生存和总生存均未显示出著性差异。结论外周血DNA EGFR基因第1内含子中CA-SSR多态性可以用于临床预测晚期非小细胞肺癌患者吉非替尼的近期疗效。     

Prediction of epidermal growth factor receptor mutations in the plasma/pleural effusion to efficacy of gefitinib treatment in advanced non-small cell lung cancer

Purpose  

Recently, mutations in the epidermal growth factor receptor (EGFR) gene were reported to correlate with EGFR tyrosine kinase inhibitor response in advanced non-small cell lung cancer (NSCLC). In this study, we attempted to detect EGFR mutations in plasma and pleural effusion samples and to make clear its correlations with gefitinib response and survival in NSCLC patients.     

Clinical outcomes of advanced non-small cell lung cancer patients screened for epidermal growth factor receptor gene mutations

Purpose  

To evaluate the relationship between the epidermal growth factor receptor (EGFR) mutation status and the effectiveness of gefitinib monotherapy or chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).     

Afatinib in first-line setting for NSCLC harbouring common EGFR mutations: new light after the preliminary results of LUX-Lung 7?

The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed dramatically the history of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Several randomized prospective trials confirmed the superiority of these target agents about survival and response rate when comparing with platinum-based chemotherapy. Knowledge about EGFR mutations increased gradually during the development of target agents and different clinical trials. EGFR mutations cannot be considered all equal, but different entities should be considered in our clinical practice: exon 19 deletions, exon 21 mutation (L858R) and uncommon mutation (exon 20, exon 18 and double mutation). Nowadays, we dispose of three different EGFR TKIs (afatinib, erlotinib and gefitinib) approved for the treatment for first-line treatment of patients di NSCLC carrying EGFR, that was compared only by indirect analysis, producing data not always clear and convincing. This research highlight is an overview of data about EGFR TKIs in first-line setting, focusing on differences about exon 19 deletions and L585R mutation in patients treated with different TKIs. In addition, we report the preliminary results of the first head-to-head randomized clinical trial between two different EGFR TKIs, the LUX-Lung 7 (LL7) that compared afatinib and gefitinib showing interesting results.     

吉非替尼对EGFR基因突变型晚期肺癌患者的影响

目的探讨聚合酶链反应-单链构象多态性（PCR-SSCP）技术检测晚期肺癌患者表皮生长因子受体（EGFR）基因突变的敏感性,观察靶向性药物吉非替尼对EGFR基因突变型肺癌患者的临床疗效。方法从54例晚期肺癌患者的肿瘤组织中提取DNA,用PCR—SSCP技术检测其EGFR基因突变情况;并对EGFR基因突变患者进行吉非替尼靶向治疗。结果肺癌组织中检出EGFR基因突变28例,突变率为51．9％;EGFR基因突变多见于女性和肺腺癌患者。28例EGFR基因突变型患者行吉非替尼治疗后的客观有效率为53．6％,病情控制率为92．9％;其生存率1a以上57．1％,2a以上28．6％,3a以上14．3％。结论PCR-SSCP检测肺癌EGFR基因突变具有高度敏感性,以其EGFR基因突变结果为依据对晚期肺癌患者选用靶向治疗,有明显疗效。     

BIM与EGFR突变非小细胞肺癌吉非替尼耐药的关系

BIM是Bcl-2中含BH3碱基亚家族的成员,是一种重要促凋亡调节蛋白.表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者对EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)治疗敏感、疗效显著,但无论近期疗效如何,最终患者都不可避免地产生耐药及病情进展.BIM参与许多癌细胞(乳腺癌、肺癌、骨肉瘤、黑色素瘤)凋亡.近年来,有研究发现BIM表达与EGFR突变NSCLC吉非替尼耐药有关.因此,了解BIM与EGFR-TKIs耐药关系有利于临床指导.本文综述了近年来BIM与EGFR突变NSCLC吉非替尼耐药的关系.     

Dramatic response to osimertinib combined with crizotinib in EGFR T790 M mutation only in blood and Met amplification only in tumor tissue expressive non-small cell lung cancer: A case report

Rationale:Besides the T790 M mutation, it may coexist with bypass pathway activation in real clinical cases for patients with EGFR mutations who resisted to the first- and second-generation tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). There are limited clinical trial data describing the efficacy of osimertinib combined with MET inhibition in EGFR T790M-mutant NSCLC patients with Met amplification.Patient concerns:A non-smoking 53-year-old male patient with lung adenocarcinoma underwent gefitinib, afatinib, and osimertinib combined with crizotinib treatment and developed different EGFR resistance mutations.Diagnoses:The patient was diagnosed with lung adenocarcinoma (stage cT4N2M0, IIIB). After resistance to the therapy targeting EGFR exon 21 L858R point mutation, T790 M mutation was detected in liquid biopsy and Met amplification was detected via tissue biopsy by next-generation sequencing (NGS).Interventions:The patient received systemic treatments, including chemotherapy, gefitinib, afatinib, and osimertinib combined with crizotinib.Outcomes:The patient died of multisystem organ failure and had an overall survival of 24 months.Lessons:Although osimertinib combined with crizotinib therapy showed dramatic tumor shrinkage in both the primary tumor and bone metastasis to an EGFR T790M-mutant NSCLC patient with MET amplification, the progression-free survival (PFS) was only two months.     

变性高效液相色谱法检测非小细胞肺癌患者外周血及肿瘤组织表皮生长因子受体突变

目的 建立变性高效液相色谱(DHPLC)法检测晚期非小细胞肺癌(NSCLC)患者外周血与肿瘤组织中表皮生长因子受体(EGFR)基因外显子19和21突变的技术平台.方法 同时收集2004年4月至2007年1月在北京肿瘤医院接受治疗的230例晚期NSCLC患者的血浆和肿瘤组织标本,采用DHPLC法检测EGFR外显子19和21突变并用测序法验证,应用x2检验分析EGFR突变与患者临床病理特征的关系,以调整比值比(OR)及95%可信区间(CJ)表示相对危险度,所有统计检验均为舣侧概率检验.分析在血浆和肿瘤组织标本中基因突变的一致性及DHPLC法与测序法的一致性.结果 230例血浆标本中EGFR突变率为34.3%(79/230),肿瘤组织中为33.5%(77/230).血浆和肿瘤组织突变阳性检出一致性为79.7%(63/79,k值为0.74).与测序法相比,DHPLC法的灵敏度和特异度分别为96.9%和91.9%(k值为0.88).肿瘤组织及外周血中EGFR突变与病理类型(OR=3.38,95%CI 1.81～6.36,P＜0.05)、吸烟史(OR=1.61,95% CI 1.13～2.28,P＜0.05)相关,而与年龄、性别、病理分期无明显相关性.结论 晚期NSCLC患者血浆EGFR突变率与肿瘤组织的突变率具有高度一致性,DHPLC法可作为EGFR突变检测的初筛方法.