盐酸埃克替尼在晚期肺鳞癌患者中生存分析研究

发布时间：2018-01-03 00:07

本文关键词：盐酸埃克替尼在晚期肺鳞癌患者中生存分析研究　出处：《北京协和医学院》2017年博士论文　论文类型：学位论文

【摘要】：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)靶向治疗被广泛应用于晚期肺腺癌患者中,尤其是伴有EGFR基因突变的肺腺癌患者,而关于EGFR-TKI在晚期肺鳞癌患者中应用仍存在很多争议。本研究第一章通过回顾性研究分析在未选择的晚期肺鳞癌患者中服用EGFR-TKI盐酸埃克替尼治疗的无进展生存时间(progression free survival,PFS)和总生存时间(overall survival,OS)。肺鳞癌EGFR突变率远远低于肺腺癌EGFR突变率,关于EGFR突变型肺鳞癌患者选择EGFR-TKI治疗较肺腺癌患者疗效差异存在争议,认为肺鳞癌患者选择TKI较腺癌效果差,本研究第二章通过比较EGFR突变型肺鳞癌和肺腺癌患者服用盐酸埃克替尼治疗的生存时间来验证这个论点。方法回顾性分析2013年6月至2016年6月服用盐酸埃克替尼治疗的肺鳞癌患者,纳入标准:年龄≥18岁;已签署知情同意书;病理证实为肺鳞癌;临床分期为IIIB或IV期;KPS评分≥60分;适宜的骨髓、肝肾功能;接受盐酸埃克替尼治疗进入慈善赠药范围。排除标准:盐酸埃克替尼联合化疗患者除外;有严重心肺疾病;有习惯性腹泻或便秘等影响药物吸收的胃肠道疾病;妊娠或哺乳。患者治疗期间定期复诊行体格检查、影像学及常规实验室检查。电话随访病人生存时间,截止日期为2017年4月。主要结局指标为PFS,次要结局指标为OS、客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)。生存分析采用Kaplain-Meier法计算;单因素生存时间差异采用Log-rank法,多因素分析采用Cox比例风险模型;组间、组内比较及不同因素的客观有效率比较采用卡方比较。检验水准确定P0.05为有统计学差异(Cox比例风险模型中P0.1)。回顾性分析2013年6月至2016年6月服用盐酸埃克替尼治疗的肺腺癌患者,纳入标准:病理证实为肺腺癌;基因检测EGFR为突变型;余同鳞癌。排除标准同鳞癌。随访截止日期为2017年4月。选择合适的肺腺癌患者与EGFR突变型肺鳞癌患者进行倾向性评分1:1比例匹配,匹配因素:年龄、性别、临床分期、KPS评分、吸烟情况、EGFR基因突变类型、治疗线数,卡钳值0.03,比较两组人群的生存时间。结局指标及统计方法同鳞癌,检验水准确定P0.05为有统计学差异。结果487例肺鳞癌患者服用盐酸埃克替尼治疗,中位无进展生存时间为13.0月(95%CI 12.2-13.8),中位总生存时间为16.0月(95%CI 14.7-17.3),1年生存率为55.4%,2年生存率为22.8%,客观缓解率为41.3%,疾病控制率为99.8%。多因素Cox逐步回归分析中肺鳞癌KPS评分和治疗疗效对无进展生存时间影响有显著性差异(P=0.063,P=0.001),同时对总生存时间影响亦有显著性差异(P=0.018,P=0.003)。患者的不良反应以皮疹、腹泻、肝酶升高为主。156例EGFR突变型肺鳞癌和肺腺癌患者服用盐酸埃克替尼治疗,其中肺鳞癌78例,肺腺癌78例,中位无进展生存时间分别为12.7月(95%CI 10.4-15.0)和15.8月(95%CI 12.4-19.2),差异无统计学意义(P=0.275);中位总生存时间分别为18.5月(95%CI14.4-22.6)和24.2月(95%CI不能计算),差异无统计学意义(P=0.150);1年生存率分别为53.8%和61.5%(P=0.297),2年生存率分别为26.7%和30.9%(P=0.191);客观缓解率分别为48.7%和59.0%(P=0.199)。肺鳞癌和肺腺癌亚组分析中EGFR-TKI治疗线数对无进展生存时间和总生存时间影响有显著性差异(P=0.024,P=0.018)。结论盐酸埃克替尼在晚期肺鳞癌患者中疗效佳,可延长肺鳞癌患者生存时间;EGFR突变型晚期肺鳞癌和肺腺癌患者对盐酸埃克替尼治疗有效率无显著性差异。
[Abstract]:Background and objective: epidermal growth factor receptor tyrosine kinase inhibitors (epidermal growth factor receptor-tyrosine kinase inhibitors, EGFR-TKIs) targeting has been widely applied in the treatment of patients with advanced lung adenocarcinoma, especially with EGFR gene mutation in patients with lung adenocarcinoma, and on the application of EGFR-TKI in advanced lung squamous cell carcinoma is still controversial in this study. The first chapter by retrospective analysis in unselected patients with advanced lung squamous cell carcinoma with EGFR-TKI icotinib treatment progression free survival time (progression free, survival, PFS) and overall survival (overall, survival, OS). EGFR mutation rate is far lower than that of lung squamous cell carcinoma of lung adenocarcinoma EGFR mutation, EGFR mutation of a dispute variant of squamous cell lung cancer treated by EGFR-TKI with lung adenocarcinoma patients differences, that patients with squamous cell carcinoma of lung adenocarcinoma TKI with poor results, on the second Chapter through the comparison of the EGFR mutant lung cancer patients taking icotinib hydrochloride in the treatment of the survival time to verify this argument. Methods a retrospective analysis from June 2013 to June 2016 taking icotinib hydrochloride in the treatment of lung squamous cell carcinoma patients with inclusion criteria: 18 years of age or older; informed consent; pathology of lung squamous cell carcinoma the clinical stage was IIIB; or IV; KPS score more than 60 points; liver and kidney function for bone marrow; receive icotinib hydrochloride in the treatment of entering the charity donated medicine. Exclusion criteria: icotinib combined with chemotherapy in patients with severe pulmonary disease except; center of gravity; habitual diarrhea or constipation and other gastrointestinal effects of drug absorption tract disease; pregnancy or lactation. Regular follow-up visits for patients during physical examination, imaging and routine laboratory examination. The survival time of patients with telephone follow-up, the deadline for April 2017. The main result indicators for PFS, Secondary outcome measures were OS, objective response rate (objective response, rate, ORR), disease control rate (disease control, rate, DCR). Survival analysis using Kaplain-Meier method; single factor survival difference by Log-rank method, multivariate analysis using Cox proportional hazard model; group, group comparison and different objective factors the efficiency compared with the chi square test level. P0.05 was identified as statistically significant (P0.1 Cox proportional hazard model). A retrospective analysis from June 2013 to June 2016 taking icotinib hydrochloride in the treatment of patients with lung cancer, inclusion criteria: pathology of lung adenocarcinoma; gene detection for EGFR mutant; Yu with squamous cell carcinoma. Exclusion criteria with squamous cell carcinoma. The deadline for follow-up in April 2017. The right lung adenocarcinoma patients with EGFR mutant lung squamous cell carcinoma patients choose the propensity score matched 1:1, match factors: age, gender, clinical Stage, KPS score, smoking status, EGFR gene mutation type, treatment line number, caliper value 0.03, the two groups were compared. The survival time of outcome indicators and statistical methods with squamous cell carcinoma, test the level of P0.05 was determined. Results there were significant differences in 487 cases of lung squamous cell carcinoma patients taking icotinib therapy, the median progression free survival time was 13 months (95%CI 12.2-13.8), the median survival time was 16 months (95%CI 14.7-17.3), the 1 year survival rate was 55.4%, 2 year survival rate was 22.8%, the objective response rate was 41.3%, the disease control rate was 99.8%. multivariate Cox regression analysis of KPS score and curative effect in the treatment of lung squamous cell carcinoma was significant the difference in progression free survival time (P=0.063, P=0.001), influence and impact on the total survival time significantly difference (P=0.018, P=0.003). The adverse reactions of patients with skin rash, diarrhea, liver enzymes increased.156 cases of EGFR mutant lung squamous cell carcinoma and adenocarcinoma of the lung Patients taking icotinib treatment, including 78 cases of lung squamous cell carcinoma, 78 cases of lung adenocarcinoma, the median progression free survival time was 12.7 months (95%CI 10.4-15.0) and 15.8 months (95%CI 12.4-19.2), the difference was not statistically significant (P=0.275); the median overall survival time was 18.5 months (95%CI14.4-22.6) and 24.2 April (95%CI not calculated), the difference was not statistically significant (P=0.150); the 1 year survival rates were 53.8% and 61.5% (P=0.297), the 2 year survival rates were 26.7% and 30.9% (P=0.191); objective remission rates were 48.7% and 59% (P=0.199). Lung squamous cell carcinoma and lung adenocarcinoma subgroup analysis effect EGFR-TKI treatment line number on progression free survival and overall survival time had significant difference (P=0.024, P=0.018). Conclusion icotinib in advanced squamous cell lung cancer patients with good curative effect, can prolong the survival time of patients with lung squamous cell carcinoma; EGFR mutant of hydrochloric acid had advanced squamous cell carcinoma and adenocarcinoma of lung cancer patients There was no significant difference in the rate of efficacy of the treatment of the treatment of the treatment.

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R734.2

【相似文献】