吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因敏感突变晚期NSCLC患者的疗效观察

目的:观察吉非替尼、厄洛替尼与埃克替尼在EGFR基因敏感突变晚期非小细胞肺癌(NSCLC)患者一线治疗中的疗效差异。方法:收集2013年5月—2014年12月间在我院接受治疗的76例EGFR基因突变的晚期NSCLC患者,随机分为三组,A组接受吉非替尼治疗,250 mg,1次/d,空腹口服;B组接受厄洛替尼治疗,150 mg,1次/d,餐前1 h口服;C组接受埃克替尼治疗,125 mg,3次/d,评价疗效及安全性。结果:吉非替尼组、厄洛替尼组和埃克替尼组的客观有效率（ORR）分别为26.9%、34.6%和45.8%;疾病控制率（DCR）分别为61.5%、73.0%和79.2%。三组之间的有效率和疾病控制率差异无统计学意义(P＞0.05）。三组的无进展生存时间（PFS）分别为9.5个月、10个月和9.5个月;19号外显子缺失突变型患者中,三组的PFS分别为8.5个月、12个月和9个月;21号外显子L858R错义突变型患者中,PFS分别为9.5个月、8.5个月和7个月,三组之间无统计学差异(P＞0.05）。结论:吉非替尼、厄洛替尼与埃克替尼治疗EGFR基因突变的晚期NSCLC疗效相似,但在19号外显子缺失突变型患者中,厄洛替尼略显优势。     

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。     

厄洛替尼单药治疗EGFR突变的晚期NSCLC患者试验汇合分析

背景与目的 厄洛替尼被全球多个国家批准用于晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的二、三线治疗.有报道显示EGFR突变的患者应用厄洛替尼治疗疗效更好.本文拟探讨厄洛替尼单药治疗EGFR突变晚期NSCLC患者的疗效.方法 计算机检索MEDLINE(2004-2009)、CBMdjc(2004-2008)、CNKI(2004-2008),互联网检索以及纳入试验的参考文献.纳入相关临床试验,提取并汇总试验结果.结果 共纳入研究7篇,包括晚期非小细胞肺癌患者463例.厄洛替尼单药治疗EGFR突变的晚期非小细胞肺癌患者,有效率达到66%,1年生存率达到73%,2年生存率达到5396,中位生存时间23个月以上,无进展生存时间8.6个月以上.结论 在当前研究的基础上,厄洛替尼单药一线和二线治疗EGFR突变的晚期NSCLC有效率高,无进展生存期和总生存期长,可以推荐作为EGFR突变的晚期NSCLC的首选治疗.尚需要更详尽的证据评价厄洛替尼单药方案或厄洛替尼与化疗联合方案与标准含铂化疗方案在治疗晚期NSCLC中的地位.     

吉非替尼联合阿帕替尼一线治疗EGFR敏感突变的晚期非小细胞肺癌患者的疗效及安全性

目的:探讨吉非替尼联合阿帕替尼对比吉非替尼一线治疗EGFR敏感突变的晚期非小细胞肺癌患者的疗效及安全性,以明确阿帕替尼能否延迟吉非替尼的耐药时间。方法:选取2015年1月至2016年12月期间我院收治的EGFR敏感突变的晚期NSCLC患者50例进行回顾性分析,分为观察组和对照组,每组各25人。观察组:吉非替尼（0.25 g,口服,1次/日）联合阿帕替尼（0.5 g,口服,1次/日）;对照组:吉非替尼（0.25 g,口服,1次/日）。评价无进展生存时间、客观缓解率、疾病控制率和不良反应发生率。结果:观察组、对照组客观缓解率分别为76.0%、68.0%,疾病控制率分别为96%、92%。观察组的近期疗效似有优于对照组的趋势,但差异均无统计学意义。观察组中位PFS为14.3个月（95%CI 11.3~17.2）,对照组中位PFS为10.3个月（95%CI 8.5~12.0）,差异有统计学意义。观察组1年的PFS率为64%,95%CI为44.4%~83.6%;对照组为20%,95%CI为4.3%~35.6%。两组主要不良反应为皮疹、高血压、蛋白尿、消化道反应、手足综合征、肝酶升高、间质性肺炎以及乏力,最为突出的不良反应为皮疹,观察组发生率为88%,对照组为84%（P＞0.05）。两组主要不良反应有统计学差异的为1-4度的高血压（P=0.004）、蛋白尿（P=0.027）、手足综合征（P=0.040）,但严重不良反应（3-4度）均无统计学差异。结论:吉非替尼联合阿帕替尼一线治疗EGFR基因敏感突变的晚期NSCLC患者似乎是一种有效且耐受良好的治疗策略,可能延迟吉非替尼的耐药时间,还需大规模多中心的临床随机对照试验证实。     

厄洛替尼二线治疗晚期肺腺癌的临床观察

目的观察厄洛替尼单药治疗化疗失败的晚期肺腺癌的疗效及毒副反应。方法 21例晚期肺腺癌口服厄洛替尼,连服2个月后评价近期疗效及毒副反应。结果 21例中PR 5例,SD 10例,PD 6例,有效率为23.80%;疾病控制率为71.43%;中位肿瘤进展为5.6个月;中位生存期为11.7个月。主要的毒副反应为皮疹、皮肤瘙痒、腹泻、恶心,多为Ⅰ-Ⅱ度,对症处理后可缓解。结论厄洛替尼单药治疗化疗失败的晚期肺腺癌患者疗效好,能延长其生存时间和提高生活质量,且毒副反应轻。     

吉非替尼与厄洛替尼治疗非小细胞肺癌的疗效观察

目的 探讨吉非替尼与厄洛替尼治疗非小细胞肺癌(NSCLC)的临床疗效.方法 选取2018年12月至2020年12月间建瓯市立医院收治的68例NSCLC患者,采用随机数字表法分为观察组和对照组,每组34例.对照组患者采用厄洛替尼治疗,观察组患者采用吉非替尼治疗,比较两组患者的临床疗效、细胞免疫功能及不良反应.结果 观察组...     

吉非替尼与厄洛替尼治疗 EGFR19／21外显子突变非小细胞肺癌的临床效果比较

目的：比较吉非替尼与厄洛替尼治疗表皮生长因子受体（EGFR）19／21外显子突变非小细胞肺癌（NSCLC）的临床效果。方法选取2013年5月至2014年12月于我院诊断为 EGFR19／21外显子突变 NSCLC 患者242例,以年龄、性别、吸烟史、美国东部肿瘤协作组行为状态（ECOG PS）评分及EGFR 突变类型配对后随机分为 A、B 两组。A 组患者（n ＝121）接受吉非替尼药物治疗,B 组患者（n ＝121）接受厄洛替尼药物治疗。根据实体瘤疗效评价标准（RECIST）评估患者的总缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）。Cox 回归单变量和多变量分析 PFS 的独立危险因素。对将研究药物作为一线治疗的63例 NSCLC 患者进行亚组分析,评价 A、B 两组的药物不良反应及生命质量。结果 A、B 两组的中位 PFS 分别是11．6个月和9．5个月,差异无统计学意义（HR ＝0．39,P ＞0．05）。两组患者的 ORR 和 DCR 分别为76．9％、74．4％（χ2＝1．03,P ＝0．58）和90．1％、86．8％（χ2＝1．46,P ＝0．31）。ECOG PS≥2（HR ＝2．60,95％CI 为1．54～4．43,P ＝0．001）和非腺癌（HR ＝3．61,95％CI 为1．54～8．66,P ＝0．003）是 PFS 欠佳的独立危险因素。对于将两种药物作为一线治疗的患者,A、B 两组的 ORR 分别为76．6％、90．2％（χ2＝0．83,P ＝0．12）,中位 PFS 分别为11．6个月、14．4个月（HR ＝0．59, P ＞0．05）,差异无统计学意义。不良反应方面,两组情感功能（F ＝10．27,P ＝0．03）、腹泻（F ＝10．24, P ＝0．03）及疼痛（F ＝9．02,P ＝0．04）差异有统计学意义。A、B 两组患者接受药物治疗后各项生命质量评分均较治疗前得到改善,且大部分差异有统计学意义（P ＜0．05）。结论对于 EGFR19／21外显子突变 NSCLC,吉非替尼和厄洛替尼两种药物耐受性良好,表现出相似的临床疗效。     

吉非替尼治疗厄洛替尼致间质性肺炎后进展的晚期肺鳞癌１例

患者男性,61岁。2003年2月22日行"左肺下叶切除术",术后病理:肺鳞癌,支气管旁淋巴结转移(1/5)。术后给予4周期NP方案(长春瑞滨+顺铂)化疗及纵隔放疗,病灶控制良好。2004年11月因"左肾上腺转移癌"行左肾上腺切除术,病理检查示:差分化鳞癌,送检肾门淋巴结未见癌转     

厄洛替尼二线治疗非小细胞肺癌临床疗效观察

背景与目的 近年来随着厄洛替尼在临床中的应用,已经显现出其特有的优势.本研究旨在进一步评价厄洛替尼用于二线治疗Ⅲb/Ⅳ期非小细胞肺癌患者的疗效和不良反应.方法 研究对象为2007年3月-2009年1月收治的曾经接受过1个-2个化疗方案治疗失败或复发的Ⅲb/Ⅳ期的非小细胞肺癌患者,给予厄洛替尼口服150mg/d,直至疾病进展;观察近期疗效和不良反应,进行随访并进行生存分析.结果 16例患者中.CR 0例(0%),PR2例(12.5%),SD 5例(31.2%),PD9例(56.2%),总有效率(CR+PR)为12.5%,疾病控制率(CR+PR+SD)为43.7%;全部病例随访1-22个月,2例至2009年1月仍然存活,随访率100%.总体平均生存期达到10.25(3-22)个月,中位生存期为9个月,1年生存率为13.3%.主要的毒副反应为皮疹、腹泻、食欲减低、肝功能损害等,发生率分别为93.7%、68.7%、43.7%、18.7%.结论 厄洛替尼可有效治疗晚期复治NSCLC患者,且耐受性良好.     

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.     

Cerebrospinal fluid concentration of gefitinib and erlotinib in patients with non-small cell lung cancer

Purpose

Several cases have been reported in which central nervous system (CNS) metastases of non-small cell lung cancer (NSCLC) resistant to gefitinib were improved by erlotinib. However, there has been no study in which cerebrospinal fluid (CSF) concentrations of gefitinib and erlotinib are directly compared. Thus, we aimed to compare them.

Methods

We examined 15 Japanese patients with NSCLC and CNS metastases with epidermal growth factor receptor gene mutations who received CSF examinations during epidermal growth factor receptor-tyrosine kinase inhibitors treatment (250?mg daily gefitinib or 150?mg daily erlotinib). Plasma and CSF concentrations were determined using high-performance liquid chromatography with tandem mass spectrometry.

Results

The concentration and penetration rate of gefitinib (mean?±?standard deviation) in the CSF were 3.7?±?1.9?ng/mL (8.2?±?4.3?nM) and 1.13?±?0.36?%, respectively. The concentration and penetration rate of erlotinib in the CSF were 28.7?±?16.8?ng/mL (66.9?±?39.0?nM) and 2.77?±?0.45?%, respectively. The CSF concentration and penetration rate of erlotinib were significantly higher than those of gefitinib (P?=?0.0008 and <0.0001, respectively). The CNS response rates of patients with erlotinib treatment were preferentially (but not significantly) higher than those with gefitinib treatment. (1/3 vs. 4/7, respectively). Leptomeningeal metastases in one patient, which were refractory to gefitinib, dramatically responded to erlotinib.

Conclusions

This study suggested that higher CSF concentration could be achieved with erlotinib and that erlotinib could be more effective for the treatment for CNS metastases, especially leptomeningeal metastases, than gefitinib.     

Impact of physical size on gefitinib efficacy in patients with non-small cell lung cancer harboring EGFR mutations

Gefitinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations. The approved dosage is 250 mg/body/day without adjustment for physical size such as body surface area (BSA), and the impact of physical size on the efficacy of gefitinib has not been evaluated. Here, we sought to clarify this issue using a retrospective cohort. We reviewed the medical records of patients with consecutive advanced NSCLC harboring EGFR mutations who underwent gefitinib monotherapy at Okayama University Hospital. In total, 101 patients were included in this study, and the median BSA in this cohort was 1.5 m². The median progression-free survival (PFS) of the patients with higher BSA (≥1.5 m²) was significantly worse than that of those with lower BSA (<1.5 m²) (10.4 vs. 18.0 months; p = 0.019, log-rank test). Multivariate analysis also showed a significant impact of BSA on PFS (hazards ratio, 2.34; 95% confidence interval, 1.78–2.89; p = 0.002). By contrast, no significant association between BSA and PFS was observed in those undergoing cytotoxic chemotherapy (4.0 vs. 5.1 months; p = 0.989, log-rank test), suggesting that BSA is a predictive, rather than a prognostic, marker for gefitinib therapy in EGFR-mutated NSCLC. In conclusion, BSA affected PFS in patients with EGFR-mutated NSCLC who underwent gefitinib monotherapy, suggesting the need for appraisal of BSA-based dose adjustment, even for this molecular target-based therapy.     

皮疹与厄洛替尼治疗晚期非小细胞肺癌疗效相关性研究

背景与目的:厄洛替尼(erloti nib)是治疗非小细胞肺痛(non-smaIl cell lung cancer,NSCLC)的一种靶向性抗肿瘤约物,皮疹是使用厄洛替尼的主要不良反应,本研究旨住探讨不同程度皮疹与厄洛替尼治疗晚期NSCLC疗效是否存在相关性.方法:对接受过1个周期以上含铂化疗方案失败的晚期NSCLC患者,每日口服150 mg厄洛替尼直至疾病进展,将出现0、1～2、3度皮疹患者分为3组,观察出现不同程度皮疹的患者接受厄洛替尼治疗后的疗效和生存时间.采用Kaplan-Meier法分析比较各组间的生存率差异.结果:0度皮疹组共自3例,有效率为0(0/3),1～2度皮疹组有36例,有效率为22.2%(8/36),3度皮疹组有9例,有效率为88.8%(8/9),各皮疹组之间有效率差异具有统计学意义(P<0.001).1～2度皮疹出现中位时间为7 d,3度皮疹出现中何时间为21 d.0、1～2和3度皮疹组的中位无进展时间分别为2、4和10个月,各组之间差异无统计学意义(P=0.067).中位生存时间分别为5、6和23个月,各组之间差异亦无统计学意义(P=0.146).0～2度和3度皮疹组中位无进展生存时间分别为3和10个月,2组之间差异有统计学意义(P=0.036);中位生存时间分别为6和23个月,2组之间差异无统计学意义(P=0.073).结论:对工不同程度皮疹与厄洛替尼治疗晚期NSCLC有效率之间存在一定相关性,皮疹较重患者有效率较高,3度皮疹患者无进展生存时间长于其他患者.     

吉非替尼治疗晚期非小细胞肺癌

目的评价吉非替尼作为二线和二线以上方案治疗晚期非小细胞肺癌(NSCLC)的临床价值。方法符合入组条件的156例患者采用吉非替尼治疗,口服,每天1次,每次250mg,持续服用直到疾病进展或出现不可耐受的毒副反应。结果154例患者可评价疗效,总有效率(RR)为28.6%(44/154),95% CI为21.6%～31.6%;临床受益率为89.6%(138/154),95% CI为84.8%～94.4%。有效患者的中位缓解时间为7.5个月(95% CI为3.9～12.1个月),中位肿瘤进展时间(TTP)为5.1个月(95% CI为3.4～6.6个月),中位总生存期(OS)为10个月(95% CI为7.9～12.1个月),1年生存率为41.0%(95% CI为33.3%～48.7%)。腺癌患者的有效率显著高于鳞癌患者(P=0.026)。其中,鳞癌患者肿瘤进展的风险是腺癌的1.7倍(95% CI为1.1～2.6,P=0.011);男性死亡的风险是女性的2.0倍(95% CI为1.0～2.6,P=0.002)。154例患者中,63例(40.9%)患者至少出现了一种药物相关毒副反应,但多数较轻,且可逆,发生率最高的是皮疹(26.3%),多伴发皮肤干燥和瘙痒。结论吉非替尼作为二线及二线以上方案治疗晚期NSCLC有较好的疗效和安全性。     

Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy

Purpose

Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC).

Patients and methods

Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible.

Results

A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9 months (95% CI, 1.3-8.5) in the gefitinib arm and 3.1 months (95% CI, 0.0-6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p = 0.269; median survival (months) 4.9 vs. 3.1, p = 0.336). There was no significant difference in QOL between the two arms.

Conclusion

Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population.     

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。     

Risk of interstitial lung disease with gefitinib and erlotinib in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials

Objectives

Gefitinib and erlotinib are oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) widely used in advanced non-small cell lung cancer (NSCLC). Interstitial lung disease (ILD) events have been described with these agents, although the overall risk remains unclear. We performed a systematic review and meta-analysis to determine the incidence and the relative risk (RR) associated with the use of gefitinib and erlotinib.

Materials and methods

PubMed databases were searched for articles published from January 2000 to October 2012, and abstracts presented at the American Society of Clinical Oncology and the European Society of Medical Oncology meetings held between 2000 and 2012 were searched for relevant studies. Eligible studies included randomized controlled trials with gefitinib and erlotinib in advanced NSCLC patients. Summary incidence rates, relative risks, and 95% CIs were calculated using fixed-effects or random-effects models, depending on the heterogeneity of the included studies.

Results

15,618 patients from 29 randomized controlled trials were selected for this meta-analysis. The overall incidence for all-grade ILD events was 1.2% (95% CI, 0.9–1.6%) among patients receiving gefitinib and erlotinib, with a mortality of 22.8% (95% CI, 14.6–31.0%). Compared with controls, the RR of all-grade ILD events associated with gefitinib and erlotinib was 1.53 (95% CI, 1.13–2.08; P = 0.006) using a fixed-effects model. The RR of fatal ILD events associated with EGFR TKIs treatment was 1.96 (95% CI, 1.03–3.72, P = 0.041) compared with control patients. The analysis was also stratified for drug type, study location, treatment arm, and treatment line, but no significant differences in RRs were observed.

Conclusion

Treatment with EGFR TKIs gefitinib and erlotinib is associated with a significant increase in the risk of developing both all-grade and fatal ILD events in advanced NSCLC.