厄洛替尼治疗非小细胞肺癌脑转移初步分析

背景与目的 非小细胞肺癌(Non-small-cell lung cancer,NSCLC)脑转移较常见,预后不佳.厄洛替尼是一种表皮生长因子受体酪氨酸激酶抑制剂,多应用于治疗晚期NSCLC.本研究拟了解厄洛替尼治疗NSCLC脑转移的疗效、预后及其相关因素.方法 回顾性分析30例NSCLC脑转移患者的临床资料,所有患者均口服厄洛替尼150mg/d.直到疾病进展、死亡或发生不可耐受的副反应.结果 厄洛替尼对颅内病灶的疗效为部分缓解2例(6.7%).疾病稳定17例(56.7%).疾病控制率为63.4%,对全身病变的总体疗效为部分缓解2例(6.7%),疾病稳定5例(16.7%),疾病控制率为23.4%.年龄、性别、吸烟状况、病理类型、PS评分、脑转移数目、脑转移时间、化疗及脑部放疗与否、副反应等各亚组之间的疗效对比均未见有统计学差异.中位疾病进展时间2.4个月,中位生存期7.7个月,1年、2年生存率分别为38.4%和15.2%.单因素分析显示生存期与患者的PS评分、吸烟状况、是否进行过脑部放疗及化疔具有相关性,多因素分析则显示生存期仅与患者是否进行过脑部放疗具有相关性,与患者的吸烟状况接近有统计学意义.结论 厄洛替尼对NSCLC脑转移具有一定的疗效,接受过脑部放疗的患者具有较好的生存获益,非吸烟者的生存时间有好于吸烟者的趋势.厄洛替尼可以作为NSCLC脑转移的一种治疗选择.     

DNA直接测序技术检测EGFR基因突变指导厄洛替尼一线治疗晚期非小细胞肺癌的临床观察

目的:通过对晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者表皮生长因子受体(epi-dermal growth factor receptor,EGFR)基因突变的检测,探讨厄洛替尼(Erlotinib)一线治疗晚期NSCLC的疗效与安全性。方法:从110例NSCLC患者的肿瘤组织提取DNA,用DNA直接测序技术检测EGFR基因19、21外显子突变情况,31例EGFR基因突变患者中,30例患者口服厄洛替尼150mg/d,持续至疾病进展或发生不能耐受的药物不良反应,评价客观有效率(RR),疾病控制率(DCR),总生存(OS),无疾病进展时间(PFS),一年生存率和药物不良反应。结果:110例NSCLC组织中EGFR基因突变31(28%)例,其中19外显子缺失18(58%)例,21外显子点突变13(42%)例。EGFR基因突变率女性40%、肺腺癌33%、不吸烟者46%,高于男性、非腺癌、吸烟的病人。30例口服厄洛替尼患者,完全缓解(CR)3例,部分缓解(PR)21例,疾病稳定(SD)5例和疾病进展(PD)1例,客观有效率为80%,疾病控制率为97%,截止随访结束,仍有20例患者生存,故中位总生存未获得结果,无疾病进展时间为11.4个月,1年生存率为78%,厄洛替尼治疗晚期NSCLC最常见的不良反应是腹泻和皮疹,多为I-II级。结论:DNA直接测序检测晚期NSCLC患者EGFR基因突变具有高度敏感性,以EGFR基因突变结果为依据,一线应用厄洛替尼治疗晚期NSCLC患者,疗效明显,耐受性好,是治疗晚期NSCLC的最佳选择之一。     

厄洛替尼治疗EGFR野生型晚期非小细胞肺癌的疗效分析

目的:评价厄洛替尼治疗EGFR野生型NSCLC的疗效及安全性.方法:31名Ⅲ/Ⅳ期或术后复发,不携带EGFR敏感突变(外显子18、19、21)的NSCLC患者服用厄洛替尼(150 mg/d).结果:术后再发的,EGFR野生型的,Ⅲ期或Ⅳ期患者服用厄洛替尼(150 mg/d),1例完全缓解,4例部分缓解,8例疾病稳定.缓解率为17.2%,疾病控制率为44.8%.皮疹是最常见的不良反应(80.6%).有两名患者出现了间质性肺病.但所有这些不良反应均为可逆的,没有出现治疗相关死亡.中位无进展生存时间及中位生存时间分别为2.1个月与7.7个月.结论:厄洛替尼可能会成为化疗耐受的EGFR野生型NSCLC患者的一个替代方案.     

DNA直接测序技术检测EGFR基因突变指导厄洛替尼一线治疗晚期非小细胞肺癌的临床观察

目的：通过对晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）患者表皮生长因子受体（epi-dermal growth factor receptor,EGFR）基因突变的检测,探讨厄洛替尼（Erlotinib）一线治疗晚期NSCLC的疗效与安全性。方法：从110例NSCLC患者的肿瘤组织提取DNA,用DNA直接测序技术检测EGFR基因19、21外显子突变情况,31例EGFR基因突变患者中,30例患者口服厄洛替尼150mg/d,持续至疾病进展或发生不能耐受的药物不良反应,评价客观有效率（RR）,疾病控制率（DCR）,总生存（OS）,无疾病进展时间（PFS）,一年生存率和药物不良反应。结果：110例NSCLC组织中EGFR基因突变31（28%）例,其中19外显子缺失18（58%）例,21外显子点突变13（42%）例。EGFR基因突变率女性40%、肺腺癌33%、不吸烟者46%,高于男性、非腺癌、吸烟的病人。30例口服厄洛替尼患者,完全缓解（CR）3例,部分缓解（PR）21例,疾病稳定（SD）5例和疾病进展（PD）1例,客观有效率为80%,疾病控制率为97%,截止随访结束,仍有20例患者生存,故中位总生存未获得结果,无疾病进展时间为11.4个月,1年生存率为78%,厄洛替尼治疗晚期NSCLC最常见的不良反应是腹泻和皮疹,多为I-II级。结论：DNA直接测序检测晚期NSCLC患者EGFR基因突变具有高度敏感性,以EGFR基因突变结果为依据,一线应用厄洛替尼治疗晚期NSCLC患者,疗效明显,耐受性好,是治疗晚期NSCLC的最佳选择之一。     

厄洛替尼治疗晚期非小细胞肺癌的临床观察

目的 探讨厄洛替尼治疗晚期非小细胞肺癌(NSCLC)的疗效及毒副反应.方法 对26例晚期不能耐受化疗及不愿接受化疗的晚期NSCLC用厄洛替尼治疗,直到病变进展或出现不可耐受的毒副反应而终止,观察其疗效和毒副反应.结果 26 例晚期NSCLC中,CR 0 例,PR 5 例,SD 11例,PD 10例,有效率为19.23%,疾病控制率为61.54%.中位肿瘤进展时间为5.7个月,中位生存时间为11.5个月.主要的毒副反应为皮疹、皮肤瘙痒、腹泻和恶心呕吐,多为Ⅰ～Ⅱ度,对症处理后可缓解.结论 厄洛替尼治疗晚期NSCLC疗效明确,毒副反应轻.     

厄洛替尼治疗老年转移性非小细胞肺癌患者的临床观察

背景与目的 厄洛替尼是小分子表皮生长因子受体酪氨酸激酶抑制剂,主要用于治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC),本研究探讨厄洛替尼单药治疗老年转移性非小细胞肺癌患者的有效性与安全性.方法 33例老年NSCLC多发转移患者接受厄洛替尼150 mg/d治疗,服药至疾病进展或死亡.结果 共有30例患者可以评价疗效,无病例完全缓解(complete regression,CR),部分缓解(Partial regression,PR)6例(20%),稳定(stable disease,SD)16例(53.33%),疾病进展(progressive disease,pD)8例(26.68%).缓解率(CR+PR)为20.0%;疾病控制率(CR+PR+SD)为73.3%.腺癌组与鳞癌组中位生存期无统计学差异(13.592±1.914个月vs9.846±1.598个月,P=0.301);两组无疾病进展时间无统计学差异(7.367±0.923个月vs 6.615±1.366个月,p=0.488).多因素Cox回归分析显示.有肝脏转移、胸腔积液、脑膜转移是影响厄洛替尼治疗客观疗效而影响生存期的因素.主要不良反应为皮疹和腹泻,不需要特殊处理.结论 老年NSCLC多发转移患者对厄洛替尼的治疗能很好耐受,并有一定的生存获益.     

非小细胞肺癌脑转移厄洛替尼和吉非替尼治疗临床比较

目的比较和评价厄洛替尼和吉非替尼靶向治疗非小细胞肺癌脑转移的疗效。方法回顾性分析2009-01-01-2012-11-25广州医科大学附属第一医院81例晚期NSCLC初诊有脑转移患者和111例晚期NSCLC初诊无脑转移患者,192例患者均为肺腺癌合并EGFR基因突变,分为吉非替尼和厄洛替尼治疗组,生存分析采用Kaplan-Meier法统计,组间生存率比较采用Log-rank检验。结果初诊有脑转移患者颅内病灶,客观有效率为45.68%(37/81),疾病控制率为90.12%(73/81)。吉非替尼、厄洛替尼治疗的无进展生存期(progression-free survival,PFS)分别为9.5和9.0个月,P=0.344;不同EGFR突变类型(19外显子序列缺失突变、21外显子突变)PFS比较分别为10.4和8.6个月,P=0.408。初诊无脑转移患者PFS分别为14.0和15.0个月,P=0.369;不同EGFR突变类型的PFS分别为14.0和15.0个月,P=0.408。结论厄洛替尼和吉非替尼一线治疗肺癌EGFR突变脑转移效果无显著性差异。     

厄洛替尼治疗70例非小细胞肺癌的回顾性评价

背景与目的 厄洛替尼作为小分子EGFR酪氨酸激酶抑制剂,已经被多项国内外研究证明该药可延长非小细胞肺(non-small cell lung cancer,NSCLC)癌患者的中位无进展生存期和总生存期,并且这些生存优势在选择人群中更为明显.本研究回顾性总结了厄洛替尼在非选择NSCLC人群中的近期疗效及毒副反应,并初步观察了不同人群的疗效差异.方法 2005年7月,2009年7月之间应用厄洛替尼治疗的70例NSCLC病例,厄洛替尼每日口服1次,每次150mg.服药4周后评价近期疗效及不良反应,以后每8周评价一次.结果 70例患者中68例可评价近期疗效,CR 0例,PR 26例,RR 38.2%,SD 24例,疾病控制率(DCR)73.5%,PD 18例(26.5%).63例可评价中位无进展生存期(PFS),中位PFS 3.0个月.其中腺癌患者中位无进展生存期3.0个月,非腺癌患者为2.6个月,生存曲线存在统计学差异.非吸烟者的疗效高于吸烟者(51.7%vs 28.2%),差异有统计学意义(P=0.048).毒副反应主要有腹泻、皮疹和ILD,ILD发生率达4.3%.结论 厄洛替尼治疗非小细胞肺癌有效,并且表现出对腺癌和非吸烟人群的选择性,未观察到性别差异.多数病人毒副反应可耐受.     

吉非替尼与厄洛替尼治疗非小细胞肺癌脑转移的临床观察

目的 探讨吉非替尼与厄洛替尼治疗非小细胞肺癌脑转移的疗效。方法 回顾性分析67例EGFR突变阳性的肺腺癌脑转移患者的病历资料,患者均口服吉非替尼250 mg/天（吉非替尼组,n=38）或厄洛替尼150 mg/天（厄洛替尼组,n=29）,直至发生颅内病变进展、死亡或不可耐受的不良反应。疗效分析采用RECIST 1.1版标准,生存分析采用Kaplan-Meier法并行Log-rank检验。结果 全组颅内病变的有效率（RR）和疾病控制率（DCR）分别为44.8％和92.5％,吉非替尼组和厄洛替尼组分别为42.1％、92.1％和48.3％、93.1％（P=0.881）。颅外病变的RR和DCR分别为53.7％和95.5％,吉非替尼组和厄洛替尼组分别为52.6％、94.7％和55.2％、96.6％（P=0.932）。全组患者的中位无进展生存期（PFS）和总生存期（OS）分别为10.8个月和15.3个月,吉非替尼组和厄洛替尼组分别为10.6个月、14.8个月和11.7个月、15.7个月（P=0.720,P=0.569）。结论 吉非替尼和厄洛替尼对EGFR突变阳性的非小细胞肺癌脑转移具有较好的疗效,可以作为脑转移患者的治疗选择,两种药物在脑转移瘤的疗效及患者的预后等方面无差异。     

厄洛替尼治疗晚期非小细胞肺癌的临床研究

背景与目的 厄洛替尼在NSCLC患者中已有广泛应用,并能使部分NSCLC患者明显获益.本研究探讨厄洛替尼单药一线或二、三线治疗晚期非小细胞肺癌的临床疗效及毒副反应.方法 研究对象为2007年6月-2008年8月接受过化疗或未化疗过的Ⅲb或Ⅳ期非小细胞肺癌患者,给予厄洛替尼口服150mg/d,直至疾病进展,观察疗效及毒副反应.结果 共有42例患者入组,随访至2009年7月10日,中位随访期为17个月,依从性为100%.42例患者中CR2.4%(1/42)、PR 35.8%(15/42)、SD 47.6%(20/42)、PD 14.396(6/42)、疾病控制率(CR+PR+SD)85.7%;中位疾病进展时间和中位生存时间分别为7个月和12.2个月;1年肿瘤无进展生存率和1年生存率分别为29%和56%.毒副反应为痤疮样皮疹78.6%(33/42)、腹泻35.7%(15/42)、转氨酶升高7.1%(3/42)、急性间质性肺病2.4%(1/42).结论 不管作为一线或者二、三线治疗,厄洛替尼治疗晚期非小细胞肺癌疗效较好.毒副反应轻微,临床获益率高,能明显改善患者的生活质量.     

Final survival and safety results from a multicenter, open-label, phase 3b trial of erlotinib in patients with advanced nonsmall cell lung cancer

BACKGROUND: Erlotinib is an orally available, reversible inhibitor of epidermal growth factor receptor (EGFR) with a proven survival advantage for patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) who have failed a prior chemotherapy. This phase 3b, multicenter, open-label trial of erlotinib in patients with advanced NSCLC who had progressed after standard chemotherapy treatment was conducted to examine the efficacy and safety of erlotinib monotherapy in patients with advanced NSCLC who had developed disease progression after previous chemotherapy and to characterize the duration of survival and the response rate of erlotinib-treated patients in subpopulations defined by other patient characteristics before U.S. Food and Drug Administration approval. METHODS: A total of 229 patients were enrolled and treated with the standard dose of erlotinib (150 mg once daily). The coprimary objectives were to characterize the overall response rate (ORR) and overall survival (OS) associated with erlotinib therapy in this group and in patient subsets defined by tobacco history. Secondary objectives were to assess safety, to characterize OS and ORR in patient subpopulations, and to determine duration of time on treatment. Patients could remain on study up to 9 months after approval. RESULTS: The ORR was 8.3% (95% confidence interval [95% CI], 5.2-2.4%). The ORR in never-smokers, previous smokers, and current smokers was 28.6% (95% CI, 13.2-50.6%), 6.0% (95% CI, 3.0-10.4%), and 7.3% (95% CI, 2.0-19.0%), respectively. The median OS for all patients was 6.3 months (95% CI, 4.7-8.0 months). In previous and current smokers, the median survival was 5.2 months (95% CI, 4.2-7.3 months) and 6.3 months (95% CI, 3.6-9.2 months), respectively, and was not reached in never-smokers. The median duration of treatment was 10.6 weeks. One (0.4%) interstitial lung disease-like event was reported. CONCLUSIONS: No new safety signals were noted. The observed ORR and survival data are consistent with results from the pivotal trial BR.21.     

Phase II trial of erlotinib in patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations: additive analysis of pharmacokinetics

Background

We conducted a phase II trial of erlotinib in patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and evaluated the relationship between plasma concentration and efficacy of erlotinib.

Methods

Patients who were previously treated but naive to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), with advanced NSCLC harboring EGFR mutations, were enrolled. Erlotinib was given at 150 mg once daily until disease progression. The primary end point was objective response rate (ORR). Plasma trough levels of erlotinib were measured on Days 2 (D2) and 8 (D8) by high-performance liquid chromatography.

Results

In total, 29 patients were enrolled from September 2008 to January 2011. ORR was 61.5 % (95 % confidence interval [CI] 40.57–79.8) of 26 assessable patients. The median progression-free survival (PFS) and overall survival (OS) were 6.3 months and 16.9 months, respectively. Skin rash was observed in 24 patients, mostly at grade 1 or 2. Grade 2 pneumonitis was observed in one patient. We collected blood samples from 16 patients. The median PFS of the high and low D8/D2 ratio group was 11.2 months and 5.7 months, respectively (p = 0.044, hazard ratio = 0.301, 95 % CI 0.094–0.968).

Conclusion

Erlotinib showed an ORR comparable to that seen in previous studies for patients with NSCLC harboring EGFR mutations, although response, the primary end point, did not reach the predetermined threshold level. The D8/D2 ratio of erlotinib plasma trough levels might be a predictive factor for PFS.     

厄洛替尼对化疗失败的晚期非小细胞肺癌的疗效及安全性研究

目的：观察厄洛替尼对化疗失败的晚期非小细胞肺癌的疗效及安全性。方法：82例既往化疗失败的Ⅲ一Ⅳ期非小细胞肺癌（NSCLC）患者,均EFGR监测阳性,给予单用厄洛替尼150mg／d,服药至病情进展或出现不能耐受的不良反应,观察厄洛替尼的疗效和不良反应,对其生存期进行分析。结果：82例患者均可评价疗效,中位治疗时间为5个月（1—14个月）;客观有效率为36．5％;疾病控制率为56．1％。性别、吸烟史、Ps评分及病理类型,临床分期对疗效无统计学关联。中位肿瘤进展时间（214±26）d;中位生存期（375±21）d,1年生存率30．3％,其中肺腺癌疗效较好占30％。最常见的不良反应为皮疹（21．9％）。结论：厄洛替尼对化疗失败的中晚期非小细胞肺癌疗效确切,且不良反应轻,耐受性好。     

厄洛替尼二/三线治疗ⅢB/Ⅳ期非小细胞肺癌的临床研究

 目的 研究厄洛替尼二/三线治疗ⅢB/Ⅳ期非小细胞肺癌患者的疗效和不良反应。 方法 2006年6月~2006年12月我院收治的30例晚期非小细胞肺癌患者,口服厄洛替尼150mg/d,直到病情进展或者因不良反应不能耐受为止。 结果 30例患者0例完全缓解,7例部分缓解,16例稳定,7例进展,总缓解率7/30（23.3％）,疾病控制率23/30（76.7％）,中位生存时间（MST）11.5月,中位无疾病进展时间（PFS）8月。 结论 厄洛替尼二线/三线治疗非小细胞肺癌患者有确切疗效,不良反应较轻。     

TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer.

PURPOSE: Erlotinib is a potent reversible HER1/epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with single-agent activity in patients with non-small-cell lung cancer (NSCLC). Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC. PATIENTS AND METHODS: TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib. Random assignment was stratified by stage, weight loss in the previous 6 months, measurable disease, and treatment center. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response (OR), and duration of response. RESULTS: There were 1,059 assessable patients (526 erlotinib; 533 placebo). Median survival for patients treated with erlotinib was 10.6 v 10.5 months for placebo (hazard ratio, 0.99; 95% CI, 0.86 to 1.16; P = .95). There was no difference in OR or median TTP. Patients who reported never smoking (72 erlotinib; 44 placebo) experienced improved OS in the erlotinib arm (22.5 v 10.1 months for placebo), though no other prespecified factors showed an advantage in OS with erlotinib. Erlotinib and placebo arms were equivalent in adverse events (except rash and diarrhea). CONCLUSION: Erlotinib with concurrent carboplatin and paclitaxel did not confer a survival advantage over carboplatin and paclitaxel alone in patients with previously untreated advanced NSCLC. Never smokers treated with erlotinib and chemotherapy seemed to experience an improvement in survival and will undergo further investigation in future randomized trials.     

A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer

Purpose

There is as yet no optimal treatment regimen for patients with epidermal growth factor receptor (EGFR) gene wild-type non-small-cell lung cancer (NSCLC) that has progressed despite cytotoxic chemotherapy. This trial was performed to evaluate the efficacy and toxicity of erlotinib, a tyrosine kinase inhibitor of EGFR, in Japanese patients with EGFR wild-type tumors.

Methods

Patients with stage III/IV or postoperative recurrence of NSCLC whose tumors have wild-type EGFR were eligible. Erlotinib (150?mg/day) was administered until disease progression or unacceptable toxicity occurred. The primary end point was disease control rate (DCR).

Results

Thirty-one patients (23 men and 8 women; median age, 71?years; range, 31–89) were enrolled between January 2008 and June 2011. Twenty-one had adenocarcinoma, nine had squamous cell carcinoma, and one had large cell carcinoma. Ten, nine, eight, and four patients showed performance status 0, 1, 2, and 3, respectively. Erlotinib was administered following the median 3.1 regimens of cytotoxic chemotherapies. One patient achieved complete response, four showed partial response, and eight had stable disease. Thus, response rate was 17.2%, and DCR was 44.8%. Skin rash was the most common side effect (80.6%). Two patients developed interstitial lung disease. Nevertheless, all of these events were reversible, and there were no treatment-related deaths. The median progression-free survival and survival times were 2.1 and 7.7?months, respectively.

Conclusion

Erlotinib might be an alternative option for patients resistant to cytotoxic chemotherapy even in those with EGFR wild-type NSCLC.     

厄洛替尼治疗晚期非小细胞肺癌的临床观察

目的观察厄洛替尼治疗晚期非小细胞肺癌的疗效及不良反应。方法32例经放、化疗治疗失败的非小细胞肺癌患者,其中6例肿瘤局限于胸腔内,26例已有远处转移,厄洛替尼剂量为每天150mg,口服,每天1次,直到肿瘤进展或因不良反应不能耐受而中止治疗。结果32例患者中,完全缓解1例,部分缓解9例,稳定13例,进展9例,全组有效率为31.3%,疾病控制率为71.9%,中位生存期7.8月,1年生存率为45.3%。主要不良反应是皮疹和腹泻,不需要特殊处理。结论厄洛替尼对放、化疗失败的晚期非小细胞肺癌有较好的治疗效果,且不良反应轻。     

晚期非小细胞肺癌EGFR蛋白磷酸化、基因突变与EGFR-TKI疗效相关性的研究

背景与目的：近年来以吉非替尼和厄洛替尼为代表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-TKI),因其在晚期非小细胞肺癌(advanced non-small cell lung cancer,NSCLC)治疗中独特的临床疗效和较低的不良反应而备受关注。尽管EGFR基因突变是目前认为最确切的预测EGFR-TKI疗效的指标,但与临床疗效间并非“全或无”的关系,提示仍有其他机制参与其中。本研究旨在探讨晚期NSCLC组织标本中EGFR磷酸化酪氨酸1068(EGFR-pTyr1068)、1173(EGFR-pTyr1173)表达与EGFR基因突变的关系,及其在EGFR-TKI治疗中的疗效预测价值。方法：采用变性高效液相色谱法(denaturing high performance liquid chromatography,DHPLC)检测205例晚期NSCLC患者组织中EGFR基因突变(19、21外显子突变)情况;并采用免疫组化方法检测其EGFR-pTyr1068、EGFRpTyr1173表达。结果：晚期NSCLC患者组织中EGFR-pTyr1068和1173表达阳性率分别为80.0%(164/205)、57.6%(95/165);其表达与临床病理特征(年龄、性别、病理类型、吸烟状态、疾病分期)无相关性。全组EGFR基因突变率为44.9%(92/205),与吸烟状态有关(P=0.024),而与其他临床病理特征(性别、年龄、病理类型、疾病分期)无关。EGFR基因突变与EGFR-pTyr1068表达呈弱相关性(P<0.001),与EGFR-pTyr1173无相关性(P=0.297)。EGFR基因突变型患者EGFR-TKI治疗的客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)和中位无进展生存期(progress free survival,PFS)分别为48.3%(43/89)、80.9%(72/89)和8.8个月(95%CI：6.11~11.42),均明显高于EGFR基因野生型患者［16.2%(17/105)、56.2%(59/105)和2.1个月,95%CI：0.89~3.24］,差异有统计学意义(P<0.001,P<0.001,P=0.024);EGFR-pTyr1068表达阳性患者ORR和DCR分别为37.7%(58/154)和74.7%(115/154),均明显高于表达阴性患者［5.0%(2/40)和40.0%(16/40)］,差异有统计学意义(P<0.001)。EGFR-pTyr1068表达阳性患者中位PFS为7.0个月,较表达阴性患者(1.2个月)明显延长,差异有统计学意义(P<0.001)。而EGFR-pTyr1173表达与EGFR-TKI疗效呈负相关性,EGFR-pTyr1173阳性者ORR、DCR和PFS分别为27.8%(25/90)、64.4%(58/90)和4.8个月,显著低于阴性患者［37.9%(25/66)、83.3%(55/66)和7.7个月,P=0.123,P=0.007,P=0.016］。以EGFR基因突变状态分层进行亚组分析显示,在EGFR基因野生型患者中,EGFR-pTyr1068表达阳性率为69.0%(69/100),EGFR-pTyr1068表达阳性和阴性患者ORR分别为23.2%(16/69)和3.2%(1/31),DCR分别为69.6%(48/69)和35.5%(11/31),差异均有统计学意义(P=0.010,P=0.001);EGFR-pTyr1068表达阳性患者中位PFS为3.6个月,较表达阴性患者(1.2个月)明显延长,差异有统计学意义(P<0.001)。16例EGFR-pTyr1068阳性表达且对EGFRTKI有效患者,中位PFS为15.6个月(95%CI：7.28~23.9)。多因素分析显示,EGFR-pTyr1068是EGFR基因野生型患者EGFR-TKI治疗的独立疗效预测因子(OR=0.24,95%CI：0.16~0.37,P<0.001)。结论：EGFR-pTyr1068可作为晚期NSCLC患者接受EGFR-TKI治疗的有效预测因子,尤其对从EGFR基因野生型患者中筛选EGFR-TKI治疗有效者具有重要作用。