EGFR基因19del和L858R突变肺腺癌患者化疗与靶向治疗疗效比较
发布时间：2019-06-06 02:16
【摘要】：背景肺癌是常见恶性肿瘤,严重危害人类健康,其发病率及死亡率居高不下,成为威胁人类健康的首位肿瘤性死亡原因[1-3],,全球每年大约有150万人死于肺癌[4],因此对肺癌的诊断、治疗、预防等方面工作任重而道远。肺癌主要分为NSCLC和SCLC两大类[38],NSCLC主要包括腺癌(≥40%)、鳞癌(30%)、大细胞癌(10%)及其他类型肺癌[5、39]。由于肺癌早期临床表现隐匿,65%患者就诊时已发生远处转移[39],临床分期多为III期/IV期[6],失去手术根治的机会。对于EGFR基因突变肺癌患者化疗、靶向治疗为其主要治疗方式,本文主要探讨临床分期为IIIB/IV期的EGFR突变肺腺癌患者化疗与靶向治疗的疗效及生存期差异问题。目的比较EGFR 19del突变肺腺癌患者化疗与EGFR-TKIs靶向治疗疗效和生存期的差异;比较EGFR L858R突变肺腺癌患者化疗及靶向治疗疗效和生存期的差异;为进一步证实化疗与靶向治疗疗效在不同突变位点的差异性,将患者按治疗方式进行分组,比较同一治疗方式下不同位点突变患者疗效的差异,进而为不同位点EGFR突变肺腺癌患者选择最佳治疗方案提供临床依据。方法收集2010年1月至2015年12月间于第三军医大学新桥医院就诊的EGFR基因发生19del和L858R突变的病例资料完整的IIIB/IV期ECOG评分≤2分的肺腺癌患者,采用回顾性分析的方法,将病例按突变类型分为19del突变组和L858R突变组,分别对两组患者进行化疗和靶向治疗疗效(客观缓解率ORR、疾病控制率DCR)及生存期(无进展生存期PFS、总生存期OS)的研究;将病例按一线治疗方式分为化疗组和靶向治疗组,分别对两组患者进行不同突变位点的疗效和生存期差异的研究。结果一.同一位点突变不同治疗方式疗效的比较1.1共收集符合纳入标准的EGFR 19del突变病例69例,其中化疗组26例(37.68%),靶向治疗组43例(62.32%),两组患者临床资料基线一致;化疗组患者PR 8例,SD 11例,PD 7例,靶向治疗组,PR 25例,SD 16例,PD 2例,两组患者均无达CR者;化疗和靶向治疗组ORR分别为30.77%和58.14%(P=0.027);DCR分别为70.38%和95.35%(P=0.022);PFS分别为7.108个月和10.652个月(P=0.018);OS分别为24.387个月和27.600个月(P=0.170)。1.2共收集符合纳入标准的EGFR L858R突变病例68例,其中化疗组40例(58.8%),靶向治疗组28例(41.2%),两组患者临床资料基线一致;化疗和靶向治疗组ORR分别为45.0%和17.9%(P=0.020);DCR分别为95.0%和71.4%(P=0.012),PFS分别为9.901个月和6.746个月(P=0.045);OS分别为21.738个月和23.611个月(P=0.378)。二.不同位点突变同一治疗方式疗效的比较2.1化疗组患者共66例,其中19del突变26例(39.39%),L858R突变40例(60.61%),两组患者临床资料基线一致;19del突变和L58R突变组ORR分别为30.77%和45.0%(P=0.048);DCR分别为70.38%和95.0%(P=0.023);PFS分别为7.108个月和9.901个月(P=0.020);OS分别为24.387个月和21.738个月(P=0.974)。2.2靶向治疗组患者共71例,其中19del突变组43例(60.56%),L858R突变组28例(39.44%);两组患者临床资料基线一致;19del突变和L58R突变组ORR分别为58.14%和17.9%(P=0.001);DCR分别为95.35%和71.4%(P=0.011);PFS分别为10.652个月和6.746个月(P=0.022);OS分别为27.600个月和23.611个月(P=0.734)结论1.对于EGFR 19del突变肺腺癌患者,靶向治疗组的ORR、DCR及PFS均优于化疗治疗组;OS未见明显优势;2.对于EGFR L858R突变肺腺癌患者,化疗治疗组患者的ORR、DCR及PFS均较靶向治疗组有明显优势,OS优势不明显。3.对采用化疗的EGFR突变肺腺癌患者,L858R突变组的ORR、DCR及PFS较19del组有明显优势;OS优势不明显;4.对采用靶向治疗的EGFR突变肺腺癌患者,19del突变组的ORR、DCR及PFS优于L858R突变组,OS未见明显优势。5.临床实际工作中对EGFR基因突变肺腺癌患者的治疗方案宜根据其突变位点进行个体化选择使患者获得最大受益。
[Abstract]:Background Lung cancer is a common malignant tumor, which is a serious threat to human health. Its morbidity and mortality are high. It is the first cause of cancer death that is threatening human health[1-3], and about 1.5 million people die in lung cancer[4] every year, so the diagnosis and treatment of lung cancer, There is a long way to go in such areas as prevention and so on. Lung cancer is mainly divided into two categories: NSCLC and SCLC[38]. NSCLC mainly includes adenocarcinoma (40%), squamous cell carcinoma (30%), large cell carcinoma (10%) and other types of lung cancer[5,39]. In the early stage of lung cancer,65% of the patients had a distant metastasis[39], and the clinical stage was stage III/ IV[6], and the chance of radical operation was lost. In this paper, the effect of chemotherapy and targeted therapy of EGFR mutant lung adenocarcinoma in the stage of stage IIIB/ IV and the difference of survival time were mainly discussed in this paper. Objective To compare the difference of the efficacy and survival of EGFR-TKIs in the treatment of EGFR-19 del-mutant lung adenocarcinoma and to compare the difference of the efficacy and survival of the chemotherapy and targeted therapy in patients with lung adenocarcinoma with EGFR-L858R. In order to further confirm the difference of the effect of chemotherapy and targeted therapy on different mutation sites, The patients were grouped according to the treatment mode, the difference of the curative effect of different site mutation patients in the same treatment mode is compared, and the clinical basis is provided for selecting the optimal treatment scheme for patients with different positions of EGFR mutation lung adenocarcinoma. Methods The patients with lung adenocarcinoma who had an ECOG score of 19 del and L858R from January 2010 to December 2015 in Xinqiao Hospital of the Third Military Medical University were collected. The method of retrospective analysis was adopted. The cases were divided into 19 del mutation group and L858R mutation group according to the mutation type, and the treatment effect (objective response rate ORR, disease control rate DCR) and survival time (no progression-free survival PFS and overall survival time OS) of the two groups of patients were studied. The cases were divided into the chemotherapy group and the target treatment group according to the first-line treatment method, and the difference of the curative effect and the survival time of the two groups of patients with different mutation sites was studied. As a result. A total of 69 cases of EGFR 19 del mutation were collected, including 26 cases (37.68%) and 43 (62.32%) of the group. There were 7 cases of PD,25 of PR,16 of SD and 2 with PD. The ORR of chemotherapy and target group was 30.77% and 58.14%, respectively (P = 0.027), and that of DCR was 70.38% and 95.35% (P = 0.022). The PFS was 7.108 months and 10.652 months (P = 0.018), respectively. The OS was 24.387 months and 27.600 months (P = 0.170). 1.2 In total,68 cases of EGFR L858R mutation were collected, including 40 cases (58.8%) of the chemotherapy group and 28 (41.2%) of the target treatment group, and the baseline of the clinical data of the two groups was consistent; and the ORR of the chemotherapy and targeted therapy group was 45.0% and 17.9% (P = 0.020), respectively; DCR was 95.0% and 71.4%, respectively (P = 0.012), PFS was 9.901 months and 6.746 months (P = 0.045), and the OS was 21.738 months and 23.611 months (P = 0.378), respectively. II. A total of 66 patients were treated with different site mutation in the same treatment mode, including 26 (39.39%) of 19 del,40 (60.61%) of L858R, and 0.77% and 45.0%, respectively (P = 0.048), and 70.38% and 95.0% (P = 0.023), respectively. The PFS was 7.108 months and 9.901 months (P = 0.020), and the OS was 24.387 months and 21.738 months (P = 0.974). The ORR of the 19 del mutation and the L58R mutation group was 58.14% and 17.9%, respectively (P = 0.001); the DCR was 95.35% and 71.4% (P = 0.011), respectively; the PFS was 10.652 months and 6.746 months (P = 0.022), respectively; the OS was 27.600 months and 23.611 months (P = 0.734) Conclusion 1, respectively. For EGFR-19-del-mutant lung adenocarcinoma patients, the ORR, DCR, and PFS in the targeted treatment group were superior to the chemotherapy-treated group; the OS did not have a significant advantage;2. For EGFR-L858R mutant lung adenocarcinoma patients, the ORR, DCR, and PFS in the chemotherapy-treated group were significantly superior to those of the targeted treatment group, and the OS advantage was not obvious. The ORR, DCR, and PFS of the L858R mutant group were significant in the patients with EGFR mutation with chemotherapy, and the OS advantage was not obvious;4. The ORR, DCR, and PFS of the 19 del mutation group were superior to the L858R mutation group in the patients with EGFR mutant lung adenocarcinoma using the targeted therapy, and no significant advantage was observed in the OS. In the clinical practice, the treatment scheme of EGFR gene mutation in patients with lung adenocarcinoma should be individualized according to its mutation site to make the patient benefit most.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
本文编号：2493994
[Abstract]:Background Lung cancer is a common malignant tumor, which is a serious threat to human health. Its morbidity and mortality are high. It is the first cause of cancer death that is threatening human health[1-3], and about 1.5 million people die in lung cancer[4] every year, so the diagnosis and treatment of lung cancer, There is a long way to go in such areas as prevention and so on. Lung cancer is mainly divided into two categories: NSCLC and SCLC[38]. NSCLC mainly includes adenocarcinoma (40%), squamous cell carcinoma (30%), large cell carcinoma (10%) and other types of lung cancer[5,39]. In the early stage of lung cancer,65% of the patients had a distant metastasis[39], and the clinical stage was stage III/ IV[6], and the chance of radical operation was lost. In this paper, the effect of chemotherapy and targeted therapy of EGFR mutant lung adenocarcinoma in the stage of stage IIIB/ IV and the difference of survival time were mainly discussed in this paper. Objective To compare the difference of the efficacy and survival of EGFR-TKIs in the treatment of EGFR-19 del-mutant lung adenocarcinoma and to compare the difference of the efficacy and survival of the chemotherapy and targeted therapy in patients with lung adenocarcinoma with EGFR-L858R. In order to further confirm the difference of the effect of chemotherapy and targeted therapy on different mutation sites, The patients were grouped according to the treatment mode, the difference of the curative effect of different site mutation patients in the same treatment mode is compared, and the clinical basis is provided for selecting the optimal treatment scheme for patients with different positions of EGFR mutation lung adenocarcinoma. Methods The patients with lung adenocarcinoma who had an ECOG score of 19 del and L858R from January 2010 to December 2015 in Xinqiao Hospital of the Third Military Medical University were collected. The method of retrospective analysis was adopted. The cases were divided into 19 del mutation group and L858R mutation group according to the mutation type, and the treatment effect (objective response rate ORR, disease control rate DCR) and survival time (no progression-free survival PFS and overall survival time OS) of the two groups of patients were studied. The cases were divided into the chemotherapy group and the target treatment group according to the first-line treatment method, and the difference of the curative effect and the survival time of the two groups of patients with different mutation sites was studied. As a result. A total of 69 cases of EGFR 19 del mutation were collected, including 26 cases (37.68%) and 43 (62.32%) of the group. There were 7 cases of PD,25 of PR,16 of SD and 2 with PD. The ORR of chemotherapy and target group was 30.77% and 58.14%, respectively (P = 0.027), and that of DCR was 70.38% and 95.35% (P = 0.022). The PFS was 7.108 months and 10.652 months (P = 0.018), respectively. The OS was 24.387 months and 27.600 months (P = 0.170). 1.2 In total,68 cases of EGFR L858R mutation were collected, including 40 cases (58.8%) of the chemotherapy group and 28 (41.2%) of the target treatment group, and the baseline of the clinical data of the two groups was consistent; and the ORR of the chemotherapy and targeted therapy group was 45.0% and 17.9% (P = 0.020), respectively; DCR was 95.0% and 71.4%, respectively (P = 0.012), PFS was 9.901 months and 6.746 months (P = 0.045), and the OS was 21.738 months and 23.611 months (P = 0.378), respectively. II. A total of 66 patients were treated with different site mutation in the same treatment mode, including 26 (39.39%) of 19 del,40 (60.61%) of L858R, and 0.77% and 45.0%, respectively (P = 0.048), and 70.38% and 95.0% (P = 0.023), respectively. The PFS was 7.108 months and 9.901 months (P = 0.020), and the OS was 24.387 months and 21.738 months (P = 0.974). The ORR of the 19 del mutation and the L58R mutation group was 58.14% and 17.9%, respectively (P = 0.001); the DCR was 95.35% and 71.4% (P = 0.011), respectively; the PFS was 10.652 months and 6.746 months (P = 0.022), respectively; the OS was 27.600 months and 23.611 months (P = 0.734) Conclusion 1, respectively. For EGFR-19-del-mutant lung adenocarcinoma patients, the ORR, DCR, and PFS in the targeted treatment group were superior to the chemotherapy-treated group; the OS did not have a significant advantage;2. For EGFR-L858R mutant lung adenocarcinoma patients, the ORR, DCR, and PFS in the chemotherapy-treated group were significantly superior to those of the targeted treatment group, and the OS advantage was not obvious. The ORR, DCR, and PFS of the L858R mutant group were significant in the patients with EGFR mutation with chemotherapy, and the OS advantage was not obvious;4. The ORR, DCR, and PFS of the 19 del mutation group were superior to the L858R mutation group in the patients with EGFR mutant lung adenocarcinoma using the targeted therapy, and no significant advantage was observed in the OS. In the clinical practice, the treatment scheme of EGFR gene mutation in patients with lung adenocarcinoma should be individualized according to its mutation site to make the patient benefit most.
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2
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相关期刊论文 前3条
1 罗萌;徐瑜;胡义德;;EGFR基因21外显子L858R突变肺腺癌患者化疗和靶向治疗疗效的回顾性分析[J];中华肺部疾病杂志(电子版);2017年01期
2 邹晶;徐兴祥;王大新;钱桂生;;肺癌放化疗“实时”疗效评估方法的研究进展[J];中华肺部疾病杂志(电子版);2013年04期
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