晚期EGFR突变型非小细胞肺癌患者接受吉非替尼或厄洛替尼治疗的成本效益分析

背景与目的非小细胞肺癌(non-small cell lung cancer,NSCLC)靶向治疗越来越受到关注,吉非替尼和厄洛替尼均被推荐用于存在表皮生长因子受体酪氨酸激酶(epidermal growth factor receptor,EGFR)基因突变的晚期NSCLC的一线治疗。本研究旨在分析比较吉非替尼和厄洛替尼在晚期NSCLC的疗效和生存获益,以及治疗成本效益。方法回顾性分析广州医保内的66例EGFR突变型的NSCLC患者。观察疗效和记录不良反应,定期随访生存预后,并追踪治疗费用。结果总共66例可评估患者,中位无进展生存期(progression-free survival,PFS)为15.0个月。其中吉非替尼49例,厄洛替尼17例,PFS分别为17.5个月和13.0个月(P=0.459)。皮疹发生率吉非替尼组为62.3%(31/49),厄洛替尼组为94.1%(16/17)。成本-效益比率(cost-effectiveness ratio,CER)吉非替尼组为3,027元/月,厄洛替尼组为6,800元/月,增量成本-效益比率(incremental cost-effectiveness ratio,ICEA)厄洛替尼为吉非替尼的2.25倍。结论 EGFR突变的晚期NSCLC患者治疗,吉非替尼和厄洛替尼有相似的疗效和生存获益,前者不良反应可能较为轻微。广州医保下,吉非替尼成本-效益比率稍优。     

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。     

二线吉非替尼对不同表皮生长因子受体突变点位晚期非小细胞肺癌患者疗效及生存情况的影响

目的 探讨二线吉非替尼对不同表皮生长因子受体(EGFR)突变点位晚期非小细胞肺癌(NSCLC)患者疗效及生存情况的影响.方法 选取72例晚期NSCLC患者,按照不同EGFR突变点位分为两组,EGFR19外显子缺失35例为观察组,EGFR21外显子缺失37例为对照组,比较两组患者二线吉非替尼治疗的临床疗效、不良反应及生存情况.结果 观察组患者疾病控制率(DCR)、客观缓解率(ORR)分别为62.86％(22/35)、60.00％(21/35),均高于对照组的37.84％(14/37)、35.14％(13/37),差异均有统计学意义(χ2=4.504、4.462,P=0.034、0.035).两组患者不良反应发生率比较,差异均无统计学意义(P>0.05).观察组患者中位无进展生存期(PFS)为28.00个月(95％CI:17.60～38.40),优于对照组的13.00个月(95％CI:8.25～17.75),差异有统计学意义(χ2=4.033,P=0.045);观察组患者的中位总生存期(OS)为28.00个月(95％CI:20.55～35.45),优于对照组的15.00个月(95％CI:10.23～19.77),差异有统计学意义(χ2=4.419,P=0.036).结论 二线吉非替尼治疗晚期NSCLC的疗效显著,与EG-FR21外显子缺失相比,EGFR19外显子缺失治疗表现出更高的敏感性,OS、PFS更优.EGFR突变状态有助于预测晚期NSCLC接受吉非替尼治疗的效果及生存情况.     

吉非替尼一线与二线治疗E GF R突变型晚期非小细胞肺癌的疗效比较

目的：观察吉非替尼用于表皮生长因子受体（epidermal growth factor receptor,EGFR）突变型晚期非小细胞肺癌（non-small cell lung cancer,NSCLC）一线或二线治疗对患者近期疗效及生存期的影响,分析吉非替尼的最佳治疗时机。方法：回顾性分析61例EGFR突变型（外显子19或21突变）晚期NSCLC患者的病历和随访资料,其中31例患者接受吉非替尼一线治疗,30例患者接受吉非替尼二线治疗;应用Kaplan-meier法进行生存分析。结果：两组患者的性别（P＝0．717）、年龄（P＝0．849）、吸烟史（P＝0．173）、病理类型（P＝0．573）和临床分期（P＝0．668）的差异无统计学意义。吉非替尼一线较二线治疗EGFR突变型NSCLC的近期有效率及疾病控制率明显提高（RR：64．5％ vs 23．3％,P＝0．001;DCR：87．1％ vs 60．0％,P＝0．016）。吉非替尼一线和二线治疗的中位无进展生存期分别为7．6和6．4个月（P＝0．392）,中位总生存期分别为16．0和17．6个月（P＝0．606）。另外,在最终获得疾病控制的患者中,吉非替尼一线治疗组为27例,二线治疗组为18例,2组中位无进展生存期及总生存期也无明显差异（PFS：8．0 vs 9．7个月,P＝0．777;OS：17．0 vs 20．0个月,P＝0．196）。结论：吉非替尼用于EGFR突变型晚期NSCLC患者,一线较二线治疗的近期疗效明显提高,但生存获益无明显差异。     

EGFR基因突变与吉非替尼治疗晚期非小细胞肺癌的疗效和预后的关系

目的 探讨中国人群中EGFR的突变与吉非替尼治疗局部晚期或转移性非小细胞肺癌（NSCLC）的疗效和预后的关系。方法 2002年5月至2005年2月,符合人组条件的患者每日服用吉非替尼,每次250mg,直至疾病进展或出现不可耐受的毒副反应。收集患者吉非替尼治疗前的肿瘤组织,提取基因组DNA后,采用巢式PCR技术扩增EGFR基因的18—24外显子,并从正反两个方向进行DNA测序和分析。结果 有106例患者人组,肿瘤标本包括25例冰冻的新鲜组织和81例石蜡包埋组织。其中32例（30．2％）发生了突变,腺癌患者的突变率（35．9％）明显高于鳞癌患者（14．3％,P=0．033）。突变患者的治疗有效率（71．9％）明显高于无突变患者（13．5％,P〈0．01）。突变患者的中位肿瘤进展时间（15个月）明显长于无突变患者（3个月,P〈0．01）。突变患者的生存期（18．5个月）也明显长于无突变患者（6．0个月,P〈0．01）。结论 中国人群中EGFR基因突变可以较好地预测吉非替尼治疗晚期NSCLC的疗效和预后。     

EGFR基因rs2293347多态对吉非替尼治疗非小细胞肺癌临床疗效的影响

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)基因遗传变异可能影响蛋白的功能,从而影响EGFR抑制剂的疗效,本研究旨在探讨EGFR酪氨酸激酶抑制剂吉非替尼的临床疗效与靶标基因EGFR单核苷酸多态rs2293347之间的相关性。方法对88例接受过吉非替尼治疗的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者进行分析,采用限制性片断长度多态进行基因分型,分析EGFR基因rs2293347多态与患者临床疗效及预后的关系。结果 EGFR基因rs2293347多态与吉非替尼的疗效相关,携带GG基因型的患者接受吉非替尼治疗的临床获益率为71.4%,而携带GA/AA基因型的患者仅为36.0%(P=0.002)。GG基因型的患者无进展生存期也明显长于GA/AA基因型的患者(10个月vs3个月,P=0.005),但是两组的总生存时间(overall survival,OS)无统计学差异(P=0.409)。结论 EGFR基因rs2293347多态与吉非替尼临床疗效密切相关,可能成为预测吉非替尼疗效的理想的遗传标记物。     

非小细胞肺癌患者体表面积与吉非替尼疗效的关系

目的探讨表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC)患者体表面积(BSA)与口服吉非替尼疗效之间的关系。方法选取2010年1月至2016年9月间河南省内乡县人民医院收治的115例采用吉非替尼单药治疗的EGFR突变的NSCLC患者,使用Cox吉非替尼疗效与体表面积的关系。结果相比于BSA较高(≥1.5m~2)者,吉非替尼对BSA较低(<1.5m~2)患者的疗效更好。两者的总存活时间(OS)无显著差别,较低和较高BSA患者的无进展生存时间(PFS)分别是8.5个月和4.2个月,差异有统计学意义(P<0.05)。BSA对PFS具有显著影响,差异有统计学意义(P<0.05)。结论使用吉非替尼单药治疗的EGFR突变NSCLC患者的BSA越高PFS越低。     

外周血表皮生长因子受体蛋白浓度与吉非替尼治疗晚期非小细胞肺癌疗效的相关性

目的 探讨外周血中表皮生长因子受体(EGFR)蛋白表达和EGFR基因突变的相关性,及其与吉非替尼治疗晚期非小细胞肺癌(NSCLC)疗效和生存的关系.方法 收集100例接受吉非替尼单药治疗的晚期NSCLC患者的临床资料、病理组织标本和配对外周血标本.采用直接测序法检测肿瘤组织EGFR基因第19号和21号外显子的基因突变情况.采用酶联免疫吸附(ELISA)法检测外周血EGFR蛋白的表达情况.将EGFR基因突变和蛋白表达与患者的疗效和生存之间的关系进行统计学分析.结果 获得随访的患者共99例.吉非替尼治疗晚期NSCLC的有效率为51.5%,临床获益率为79.8%.99例患者标本中,有35例存在EGFR基因突变,突变率为35.4%.EGFR基因突变患者的有效率和临床获益率分别为65.7%和94.3%,均明显高于无基因突变的患者(43.8%和71.9%,均P＜0.05).EGFR基因突变患者的中位无进展生存时间(PFS)为23个月(95%CI为12.9～33.0个月),明显长于无突变的患者(10个月,95%CI为7.3～12.6个月;P=0.014).EGFR蛋白高表达(≥55.42 μg/L)患者的吉非替尼治疗临床获益率为90.0%,明显高于低表达(＜55.42 μg/L)的患者(64.1%,P=0.004).EGFR蛋白高表达患者的中位PFS为21个月(95%CI为14.3～27.6个月),明显长于低表达的患者(8个月,95%CI为5.5～10.4个月;P=0.016).EGFR蛋白表达是EGFR基因突变的独立影响因素,两者呈显著的正相关(P=0.000).结论 EGFR基因突变和外周血EGFR蛋白高表达的NSCLC患者,应用吉非替尼治疗有效.外周血EGFR蛋白表达有可能作为预测和评价吉非替尼治疗晚期NSCLC疗效和患者预后的分子生物学指标.

Abstract：

Objective To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer(NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC. Methods Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software. Results The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 μg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P=0.037; 94.3% vs. 71.9%,P=0.008). The median PFS was prolonged (23 months vs. 10 months,P=0.014). The CBR of patients with high EGFR protein expression (concentration≥55.42 μg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P=0.004), and the median PFS was prolonged (21 months vs. 8 months,P=0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive. Conclusions Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.     

EGFR-TKI一线治疗EGFR基因突变的晚期非小细胞肺癌临床观察

背景与目的研究表明,一线表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitor,EGFR-TKI)治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的客观缓解率及无进展生存期明显优于铂二联的化疗,且耐受性更好。本研究旨在分析EGFR-TKI一线治疗晚期EGFR突变阳性的NSCLC患者的疗效与耐受性。方法 54例晚期NSCLC患者肿瘤标本采用直接测序法证实EGFR活化突变(外显子19缺失或外显子21点突变),一线给予EGFR-TKI口服治疗直至疾病进展,观察疗效及不良反应,并进行生存随访。结果 54例患者外显子19缺失33例(61%),外显子21点突变21例(39%)。均一线接受EGFR-TKI治疗,总体缓解率为90%,中位无进展生存期(progression free survival,PFS)为8.3个月,中位生存期为19.5个月;外显子19缺失患者的中位PFS(9.0个月)较21点突变(7.0个月)时间长(P=0.002)。外显子19缺失患者的中位总生存期(overall survival,OS)(25.0个月)较21点突变(16.0个月)时间长(P=0.001);吉非替尼与厄洛替尼疗效相当,但吉非替尼组安全性更好;最常见的不良事件为皮疹和腹泻,有2例患者(4%)出现了3度皮肤毒性反应,2例患者(4%)出现了3度的转氨酶升高,1例患者(1%)出现了3度口腔炎。结论存在EGFR基因突变的晚期NSCLC患者一线接受EGFR-TKI治疗安全有效,且外显子19缺失比L858R突变疗效更优。     

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。     

EGFR / HER2 / HER3 expression in tumour and gefitinib treatment in Chinese patients with advanced non-small cell lung cancer

Objective: Biological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung cancer (NSCLC) treated with gefitinib are urgently needed.Methods: We analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90 Chinese patients.Platinumpretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression; EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression (TTP), and overall survival (OS).Results: A high expression (scores 2-3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively.EGFR and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated with a higher RR (35.9% vs.15.7%, P = 0.027).The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77 patients (53.8% vs.22.1%, P = 0.036).EGFR / HER2 / HER3 status was not significantly correlated with TrP or OS.Conclusion: The HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC who are candidates for gefitinib therapy     

EGFR HER2和HER3表达水平与IRESSA治疗晚期NSCLC疗效和预后的关系

目的：探讨EGFR（HER1）、HER2和HER3的表达水平与IRESSA（易瑞莎）治疗NSCLC的疗效和预后的关系。方法：2002年5月至2005年2月，符合入组条件的患者，口服IRESSA治疗．直到疾病进展或出现不可耐受的毒副反应．采用免疫组化法，评价入组前肿瘤组织中EGFR、HER2和HER3的表达情况结果：90例患者的EGFR、HER2和HER3的阳性率分别为16．7％、43.3％和21．1％总有效率为24．4％（22／90）EGFR和HER3的表达都与IRESSA的疗效无关。但HER2阳性患者的有效率显著高于阴性患者（35．9％、15．7％．P=0．027）HER2和HER3都高表达患者的有效率显著高于其余患者（53．8％、22．1％，P=0．036）.患者的中位总TFP为4．0个月，中位总OS为11．5个月，一年生存率为49％。EGFR、HER2和HER3单独表达情况对TTP、OS无影响分层分析发现．EGFR、HER2和HER3共表达情况对TTP和OS都没有影响。结论：EGFR的表达与疗效无关．对TTP和OS无影响HER2和HER3都高表达患者对IRESSA的敏感性增高，不受EGFR表达情况的干预.     

The EGFR mutation and its correlation with response of gefitinib in previously treated Chinese patients with advanced non-small-cell lung cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy of gefitinib and the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a series of Chinese patients with pretreated advanced non-small-cell lung cancer (NSCLC). METHODS: A total of 98 patients who had failed at least one platinum-based regimen received gefitinib 250 mg once daily. The mutation analysis of the EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor tissue. RESULTS: The response rate was 31.6% and the disease control rate was 67.3%. Objective response was correlated with adenocarcinoma, female gender and non-smokers. Median progress free survival (PFS) was 7.0 months, median overall survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and OS were improved among patients with adenocarcinoma, gefitinib responders and non-smokers. Active gene mutation was detected in 12 patients. Mutation rates were higher among gefitinib responders, non-smokers, patients with adenocarcinoma and female patients. OS was longer for patients with gene mutation than for patients without mutation. CONCLUSION: Gefitinib demonstrated significant antitumor activity with a favorable toxicity profile for pretreated Chinese patients with advanced NSCLC. The active mutation of the EGFR kinase domain was strongly associated with response to gefitinib and prolonged overall survival.     

Gefitinib as front-line treatment in Chinese patients with advanced non-small-cell lung cancer

PURPOSE: This phase II single arm, open label study was designed to evaluate the efficacy and toxicity of oral gefitinib (250mg) daily in previously untreated patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Eligible patients had stage IIIB or IV NSCLC with adequate organ functions, and were chemona?ve. All eligible patients were treated with oral administration of 250mg of gefitinib until intolerable toxicity, disease progression or death occurred. Responses were assessed after every 8 weeks of therapy. RESULTS: For a total of 53 patients, the objective response rate (ORR) was 32.1% and overall disease control rate (DCR) was 52.8%. Median overall and progression-free survivals (PFS) were 9.4 (95% CI, 8.8-13.3) and 3.2 months (95% CI, 1.1-5.2) months, and 1-year survival rate was 41.5%. Patients with adenocarcinoma (n=35) had a higher response rate. Adenocarcinoma, female gender (n=24), and response to gefitinib were predictive factors for better survival. The most commonly seen adverse events (AEs) were skin toxicity (54.7%), diarrhea (43.4%) and nail change (16.9%). Most AEs were mild to moderate and considered manageable. Drug-related interstitial pneumonia was clinically diagnosed in four cases (7.5%). CONCLUSIONS: Oral gefitinib, as compared to conventional chemotherapy, has comparable effect but less toxicity as a first-line treatment in Chinese patients who have advanced NSCLC, especially in those with adenocarcinoma histology. A further phase III prospective study comparing gefitinib to standard chemotherapy to define the efficacy of gefitinib is appropriate in advanced NSCLC patients.     

晚期非小细胞肺癌吉非替尼治疗性别与疗效相关性分析

目的:探讨吉非替尼对不同性别晚期非小细胞肺癌(NSCLC)患者的疗效和安全性。方法:选择化疗失败的晚期NSCLC患者74例,分为女性组(36例)和男性组(38例),应用吉非替尼进行单药治疗,口服剂量为250 mg/d。分析两组治疗疗效和安全性。结果:女性组和男性组的总有效率(47.2%vs 26.3%,P=0.062)以及中位无进展生存期(7.9个月vs 5.7个月,P=0.093)差异均无统计学意义;而其中女性腺癌患者的有效率(53.8%)与以及中位无进展生存期(10.1个月)明显优于男性鳞癌患者,差异均有统计学意义,P值均<0.05。两组的不良反应相似主要为皮疹和腹泻。结论:对于晚期NSCLC患者,在无检测表皮生长因子受体(EGFR)情况下,合理选择优势人群,应用分子靶向药物吉非替尼治疗,疗效较高,能有助于提高NSCLC临床个体化治疗水平。     

吉非替尼或多西他赛治疗一线化疗失败的非小细胞肺癌的临床分析

目的 探讨既往一线化疗失败的晚期非小细胞肺癌(NSCLC)患者接受吉非替尼或多西他赛治疗的疗效和安全性.方法 222例NSCLC患者随机分为吉非替尼组和多西他赛组,两组患者在性别、年龄、病理类型、分期等方面大致平衡.采用Kaplan-Meier法进行生存分析和比较,采用生活质量量表法评价患者治疗后生存质量的改善情况.结果 吉非替尼组和多西他赛组的中位生存时间分别为11.0个月和14.0个月(P=0.783),中位无疾病进展生存时间(PFS)分别为3.4个月和3.8个月,6个月的PFS率分别为35.1%和18.5%,客观有效率分别为21.9%和9.1%(P=0.016).吉非替尼组中,有3例(2.8%)患者因不良反应调整药物剂量;而多西他赛组中,有36例(33.3%)患者因不良反应调整药物剂量.多西他赛组中,3～4级不良反应的发生率为61.1%;吉非替尼组中,3～4级不良反应的发生率为13.1%.吉非替尼组患者在生活质量和耐受性方面也明显优于多西他赛组.结论 在既往治疗失败的晚期NSCLC患者中,吉非替尼与多西他赛的总体疗效相似,但吉非替尼的耐受性更好,患者的生活质量有所改善,是替代多西他赛治疗的重要药物之一.

Abstract：

Objective To compare the efficacy and safety of gefitinib or docetaxel in Chinese patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who had failed previous platinum-based first-line chemotherapy. Methods We retrospectively reviewed 222 Chinese NSCLC patients in the subgroup of INTEREST ( gefitinib versus docetaxel in previously treated non-small cell lung cancer) study. Survival analysis was evaluated by Kaplan-Meier method, and Functional Assessment of Cancer Therapy-Lung ( FACT-L) was used to compare the quality of life between gefitinib group and docetaxel group. Results A total of 222 patients were analyzed in this subgroup study. 107 patients were treated with gefitinib, and 115 patients treated with docetaxel. There were all balanced between the two groups in terms of sex, age, staging and pathology in patient characteristics. The median overall survival in the two groups was similar (11 months in the gefitinib group vs. 14.0 months in the docetaxel group, P = 0.783). The progression-free survival (PFS) was also similar between the two groups (median PFS: 3.4 months in gefitinib group vs. 3. 8 months in docetaxel group, P =0. 214). The response rate in gefitinib group was significantly higher than that in the docetaxel group (21.9% vs. 9.1% , P =0.016). Conclusion The efficacy of gefitinib is similar with that of docetaxel in pretreated patients with locally advanced or metastatic NSCLC, however, gefitinib is more favorable in the tolerance and quality of life improvement.     

吉非替尼或多西他赛治疗一线化疗失败的非小细胞肺癌的临床分析

目的 探讨既往一线化疗失败的晚期非小细胞肺癌(NSCLC)患者接受吉非替尼或多西他赛治疗的疗效和安全性.方法 222例NSCLC患者随机分为吉非替尼组和多西他赛组,两组患者在性别、年龄、病理类型、分期等方面大致平衡.采用Kaplan-Meier法进行生存分析和比较,采用生活质量量表法评价患者治疗后生存质量的改善情况.结果 吉非替尼组和多西他赛组的中位生存时间分别为11.0个月和14.0个月(P=0.783),中位无疾病进展生存时间(PFS)分别为3.4个月和3.8个月,6个月的PFS率分别为35.1%和18.5%,客观有效率分别为21.9%和9.1%(P=0.016).吉非替尼组中,有3例(2.8%)患者因不良反应调整药物剂量;而多西他赛组中,有36例(33.3%)患者因不良反应调整药物剂量.多西他赛组中,3～4级不良反应的发生率为61.1%;吉非替尼组中,3～4级不良反应的发生率为13.1%.吉非替尼组患者在生活质量和耐受性方面也明显优于多西他赛组.结论 在既往治疗失败的晚期NSCLC患者中,吉非替尼与多西他赛的总体疗效相似,但吉非替尼的耐受性更好,患者的生活质量有所改善,是替代多西他赛治疗的重要药物之一.     

吉非替尼或多西他赛治疗一线化疗失败的非小细胞肺癌的临床分析

目的 探讨既往一线化疗失败的晚期非小细胞肺癌(NSCLC)患者接受吉非替尼或多西他赛治疗的疗效和安全性.方法 222例NSCLC患者随机分为吉非替尼组和多西他赛组,两组患者在性别、年龄、病理类型、分期等方面大致平衡.采用Kaplan-Meier法进行生存分析和比较,采用生活质量量表法评价患者治疗后生存质量的改善情况.结果 吉非替尼组和多西他赛组的中位生存时间分别为11.0个月和14.0个月(P=0.783),中位无疾病进展生存时间(PFS)分别为3.4个月和3.8个月,6个月的PFS率分别为35.1%和18.5%,客观有效率分别为21.9%和9.1%(P=0.016).吉非替尼组中,有3例(2.8%)患者因不良反应调整药物剂量;而多西他赛组中,有36例(33.3%)患者因不良反应调整药物剂量.多西他赛组中,3～4级不良反应的发生率为61.1%;吉非替尼组中,3～4级不良反应的发生率为13.1%.吉非替尼组患者在生活质量和耐受性方面也明显优于多西他赛组.结论 在既往治疗失败的晚期NSCLC患者中,吉非替尼与多西他赛的总体疗效相似,但吉非替尼的耐受性更好,患者的生活质量有所改善,是替代多西他赛治疗的重要药物之一.     

吉非替尼治疗不同类型晚期非小细胞肺癌患者的疗效比较

背景与目的:化放疗已经很难再提高晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效.有临床研究表明分子靶向药物吉非替尼单药治疗NSCLC有效果,但个体疗效差异大.本研究旨在通过比较吉非替尼对不同类型晚期NSCLC患者的疗效差别,更好地选择目标人群.方法:选择门诊化疗失败的晚期NSCLC患者50例,分为两肺弥漫性结节组(20例)和单肺巨块组(30例),应用吉非替尼进行单药治疗,分析两组治疗疗效差别.结果:两组服药至症状改善的中位时间(4天vs.7天,P＜0.01)、疾病缓解程度和缓解率(75%vs.20%,P＜0.01),以及中位无进展生存期(9.5个月vs.3.7个月,P＜0.01)的差异均有显著性,而不良反应相似.结论:吉非替尼治疗两肺晚期弥漫性结节性NSCLC比单肺晚期巨块型NSCLC更有效,可以考虑将该药作为两肺弥漫性结节NSCLC患者复治的选择.     

Impact of HER2 and EGFR gene status on gefitinib-treated patients with nonsmall-cell lung cancer

We previously examined the relationship between epidermal growth factor receptor (EGFR) status and clinical outcomes of nonsmall-cell lung cancer (NSCLC) patients treated with gefitinib. In our study, we additionally examined HER2 status and investigate the impact of genetic status as predictors in Japanese NSCLC patients treated with gefitinib. The HER2 copy number status was determined by fluorescence in situ hybridization assay and mutation of HER2 exon 20 was determined by direct sequencing in 74 patients to investigate the relationship between molecular statuses including HER2 and EGFR and the clinical outcomes of patients treated with gefitinib. The high HER2 copy number was identified in 32 (43.2%) of 74 NSCLC patients and no HER2 exon 20 mutations were found. The high HER2 copy number was significantly associated with the sensitivity to gefitinib (p = 0.0045) and a prolonged progression-free survival (PFS) (p = 0.0089) in a univariate analysis, but not in a multivariate analysis. Multivariate analyses exhibited that the drug-sensitive EGFR mutation was an independent predictive factor of a better sensitivity to gefitinib (OR = 41.9, p = 0.002), prolonged overall survival (HR = 0.32, p = 0.019) and PFS (HR = 0.31, p = 0.0045). The high EGFR copy number might have a weak association with better response and prognosis without statistical significance. In conclusion, the drug-sensitive EGFR mutation, rather than HER2 and EGFR copy numbers, is a determinant of favorable clinical outcomes in gefitinib-treated patients with NSCLC, although the high HER2 copy number, to some extent, may influence the gefitinib effect.