奥希替尼与埃克替尼一线治疗EGFR阳性转移性NSCLC临床疗效观察

doi:10.3760/cma.j.cn371439-20221028-00014

摘要/Abstract

摘要：

目的探讨奥希替尼与埃克替尼治疗转移性非小细胞肺癌（NSCLC）在真实世界的疗效。方法回顾性分析2018年3月—2022年5月在武汉大学人民医院确诊的151例表皮生长因子受体（EGFR）阳性晚期NSCLC初诊患者的临床资料，根据治疗方法分为奥希替尼组（53例）和埃克替尼组（98例）。比较两组客观缓解率（ORR）、疾病控制率（DCR）、无进展生存期（PFS）及总生存期（OS）；采用Cox回归模型分析预后的影响因素；并按照转移部位及EGFR突变类型进行亚组分析。结果奥希替尼组和埃克替尼组患者的ORR分别为56.6%（30/53）、59.2%（58/98），差异无统计学意义（χ²=0.09，P=0.759）；两组患者的DCR分别为83.0%（44/53）、91.8%（90/98），差异无统计学意义（χ²=2.68，P=0.102）。奥希替尼组和埃克替尼组患者的中位PFS分别为11.7、11.8个月，差异无统计学意义（χ²=0.06，P=0.802）；两组患者的中位OS均为未达到，差异无统计学意义（χ²<0.01，P=0.969）。多因素分析结果显示肾上腺转移（HR=1.89，95%CI为1.04~3.41，P=0.036）为患者PFS的独立预后因素；性别（HR=2.22，95%CI为1.08~4.58，P=0.031）和肾上腺转移（HR=4.87，95%CI为1.76~13.46，P=0.002）为患者OS的独立预后因素。亚组分析结果显示，在胸膜转移（中位PFS：11.7个月比9.3个月，中位OS：未达到比未达到）、肾上腺转移（中位PFS：8.7个月比5.6个月，中位OS：20.0个月比15.3个月）、19DEL突变（中位PFS：14.5个月比13.3个月，中位OS：未达到比40.7个月）患者中，奥希替尼组倾向于有更好的生存结局；相反，在对侧肺转移（中位PFS：8.3个月比11.2个月，中位OS：未达到比40.7个月）、骨转移（中位PFS：11.7个月比11.8个月，中位OS：未达到比34.5个月）、肝转移（中位PFS：8.7个月比9.1个月，中位OS：未达到比23.8个月）、脑转移（中位PFS：11.7个月比15.3个月，中位OS：22.4个月比35.3个月）和21L858R突变（中位PFS：9.5个月比10.0个月，中位OS：22.4个月比未达到）患者中，埃克替尼组倾向于有更好的生存结局，但差异均无统计学意义（均P>0.05）。结论奥希替尼和埃克替尼对EGFR阳性晚期NSCLC患者都具有良好的治疗效果，两者均可作为一线治疗的选择。

关键词: 癌, 非小细胞肺, 奥希替尼, 埃克替尼, 表皮生长因子受体

Abstract:

Objective To investigate the real-world efficacy of osimertinib and icotinib in metastatic non-small cell lung carcinoma （NSCLC） patients. Methods A retrospective analysis was performed on clinical data of 151 newly-diagnosed patients with epidermal growth factor receptor （EGFR）-positive advanced NSCLC in Renmin Hospital of Wuhan University from March 2018 to May 2022. The patients were divided into osimertinib group （n=53） and icotinib group （n=98） according to treatment method. The objective response rate （ORR），disease control rate （DCR），progression-free survival （PFS） and overall survival （OS） were compared between the two groups. The factors influencing prognosis were analyzed by using Cox regression models. Subgroup analysis was performed according to metastatic site and EGFR mutation type. Results ORR was 56.6% （30/53） and 59.2% （58/98） for patients in the osimertinib group and icotinib group，respectively，with no statistically significant difference （χ²=0.09，P=0.759）. DCR was 83.0% （44/53） and 91.8% （90/98） for patients in the osimertinib group and icotinib group，respectively，with no statistically significant difference （χ²=2.68，P=0.102）. The median PFS was 11.7 months and 11.8 months for patients in the osimertinib group and icotinib group，respectively，with no statistically significant difference （χ²=0.06，P=0.802）. The median OS was not reached for patients in both the osimertinib group and icotinib group，with no statistically significant difference （χ²<0.01，P=0.969）. The results of multivariate analysis showed that adrenal metastases （HR=1.89，95%CI： 1.04-3.41，P=0.036） was an independent prognostic factor for PFS. Gender （HR=2.22，95%CI： 1.08-4.58，P=0.031） and adrenal metastases （HR=4.87，95%CI： 1.76-13.46，P=0.002） were independent prognostic factors for OS. The results of the subgroup analysis showed that in patients with pleural metastases （median PFS： 11.7 months vs. 9.3 months，median OS： not reached vs. not reached），adrenal metastases （median PFS： 8.7 months vs. 5.6 months，median OS： 20.0 months vs. 15.3 months），19DEL mutations （median PFS： 14.5 months vs. 13.3 months，median OS： not reached vs. 40.7 months），the osimertinib group tended to have better survival outcomes. Conversely，in patients with contralateral lung metastases （median PFS： 8.3 months vs. 11.2 months，median OS： not reached vs. 40.7 months），bone metastases （median PFS： 11.7 months vs. 11.8 months，median OS： not reached vs. 34.5 months），liver metastases （median PFS： 8.7 months vs. 9.1 months，median OS： not reached vs. 23.8 months），brain metastases （median PFS： 11.7 months vs. 15.3 months，median OS： 22.4 months vs. 35.3 months） and 21L858R mutations （median PFS： 9.5 months vs. 10.0 months，median OS： 22.4 months vs. not reached），the icotinib group tended to have better survival outcomes，but with no statistically significant differences （all P>0.05）. Conclusion Both osimertinib and icotinib have good therapeutic efficacy in patients with EGFR-positive advanced NSCLC，thus can be used as first-line treatment options.

Key words: Carcinoma, non-small-cell lung, Osimertinib, Icotinib, Epidermal growth factor receptor

宁婷婷, 胡钦勇, 李倩, 杨鹏程. 奥希替尼与埃克替尼一线治疗EGFR阳性转移性NSCLC临床疗效观察[J]. 国际肿瘤学杂志, 2023, 50(2): 65-70.

Ning Tingting, Hu Qinyong, Li Qian, Yang Pengcheng. Clinical efficacy of osimertinib and icotinib in first-line treatment of EGFR-positive metastatic NSCLC[J]. Journal of International Oncology, 2023, 50(2): 65-70.

图/表 5

表1

图1

表2

表3

表4

参考文献 16

[1]	Siegel RL, Miller KD, Fuchs HE, et al. Cancer statistics, 2022[J]. CA Cancer J Clin, 2022, 72(1): 7-33. DOI: 10.3322/caac.21708. doi: 10.3322/caac.21708
[2]	Kuijpers CCHJ, Hendriks LEL, Derks JL, et al. Association of molecular status and metastatic organs at diagnosis in patients with stage Ⅳ non-squamous non-small cell lung cancer[J]. Lung Cancer, 2018, 121: 76-81. DOI: 10.1016/j.lungcan.2018.05.006. doi: S0169-5002(18)30370-2 pmid: 29858031
[3]	Zhang J, Yu Q, He Y, et al. The cancers-specific survival of metastatic pulmonary carcinoids and sites of distant metastasis: a population-based study[J]. Technol Cancer Res Treat, 2021, 20: 15330338211036528. DOI: 10.1177/15330338211036528. doi: 10.1177/15330338211036528
[4]	Xu Z, Yang Q, Chen X, et al. Clinical associations and prognostic value of site-specific metastases in non-small cell lung cancer: a population-based study[J]. Oncol Lett, 2019, 17(6): 5590-5600. DOI: 10.3892/ol.2019.10225. doi: 10.3892/ol.2019.10225 pmid: 31186781
[5]	Gelatti ACZ, Drilon A, Santini FC. Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC)[J]. Lung Cancer, 2019, 137: 113-122. DOI: 10.1016/j.lungcan.2019.09.017. doi: S0169-5002(19)30661-0 pmid: 31568888
[6]	Harrison PT, Vyse S, Huang PH. Rare epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer[J]. Semin Cancer Biol, 2020, 61: 167-179. DOI: 10.1016/j.semcancer.2019.09.015. doi: S1044-579X(19)30302-5 pmid: 31562956
[7]	Farnsworth DA, Chen YT, de Rappard Yuswack G, et al. Emerging molecular dependencies of mutant EGFR-driven non-small cell lung cancer[J]. Cells, 2021, 10(12): 3553. DOI: 10.3390/cells10123553. doi: 10.3390/cells10123553
[8]	Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase Ⅲ, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS)[J]. J Clin Oncol, 2011, 29(21): 2866-2874. DOI: 10.1200/JCO.2010.33.4235. doi: 10.1200/JCO.2010.33.4235
[9]	Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial[J]. Lancet Oncol, 2012, 13(3): 239-246. DOI: 10.1016/S1470-2045(11)70393-X. doi: 10.1016/S1470-2045(11)70393-X pmid: 22285168
[10]	Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial[J]. Lancet Oncol, 2014, 15(2): 213-222. DOI: 10.1016/S1470-2045(13)70604-1. doi: 10.1016/S1470-2045(13)70604-1
[11]	He J, Su C, Liang W, et al. Icotinib versus chemotherapy as adjuvant treatment for stage Ⅱ-ⅢA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial[J]. Lancet Respir Med, 2021, 9(9): 1021-1029. DOI: 10.1016/S2213-2600(21)00134-X. doi: 10.1016/S2213-2600(21)00134-X
[12]	Papadimitrakopoulou VA, Mok TS, Han JY, et al. Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis[J]. Ann Oncol, 2020, 31(11): 1536-1544. DOI: 10.1016/j.annonc.2020.08.2100. doi: 10.1016/j.annonc.2020.08.2100 pmid: 32861806
[13]	Cheng Y, He Y, Li W, et al. Osimertinib versus comparator EGFR TKI as first-line treatment for EGFR-mutated advanced NSCLC: FLAURA China, a randomized study[J]. Target Oncol, 2021, 16(2): 165-176. DOI: 10.1007/s11523-021-00794-6. doi: 10.1007/s11523-021-00794-6 pmid: 33544337
[14]	Shi YK, Wang L, Han BH, et al. First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study[J]. Ann Oncol, 2017, 28(10): 2443-2450. DOI: 10.1093/annonc/mdx359. doi: S0923-7534(19)34957-9 pmid: 28945850
[15]	Gen S, Tanaka I, Morise M, et al. Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis[J]. BMC Cancer, 2022, 22(1): 654. DOI: 10.1186/s12885-022-09741-8. doi: 10.1186/s12885-022-09741-8 pmid: 35698083
[16]	Wang Y, Yuan X, Yang M, et al. Efficacy of icotinib, an EGFR tyrosine kinase inhibitor in non-small cell lung cancer patients with exon 19 deletion and exon 21 L858R: a retrospective analysis in China[J]. Pharmacology, 2021, 106(11/12): 658-666. DOI: 10.1159/000519847. doi: 10.1159/000519847

影响因素	PFS			OS
影响因素	HR值	95%CI	P值	HR值	95%CI	P值
年龄（>65岁/≤65岁）	1.25	0.83~1.87	0.290	0.87	0.42~1.80	0.699
性别（男/女）	1.59	1.07~2.36	0.021	2.11	1.05~4.25	0.036
吸烟史（有/无）	1.51	0.80~2.83	0.200	0.32	0.04~2.34	0.261
PS评分（≥2分/<2分）	1.76	1.01~3.08	0.048	1.10	0.47~2.55	0.826
EGFR突变类型（19DEL/21L858R）	0.91	0.49~1.68	0.753	0.75	0.25~2.31	0.620
临床分期（Ⅳ期/Ⅲ期）	1.14	0.61~2.14	0.679	4.61	0.63~33.78	0.133
对侧肺转移（有/无）	1.22	0.82~1.81	0.336	0.94	0.45~1.95	0.871
肝转移（有/无）	1.42	0.71~2.86	0.321	3.82	1.54~9.47	0.004
脑转移（有/无）	1.43	0.90~2.28	0.126	1.71	0.83~3.50	0.144
胸膜转移（有/无）	1.15	0.74~1.77	0.537	0.71	0.31~1.64	0.417
骨转移（有/无）	1.00	0.68~1.48	0.987	2.28	1.08~4.82	0.031
肾上腺转移（有/无）	1.96	1.09~3.53	0.025	7.21	3.21~16.18	<0.001
治疗方案（奥希替尼/埃克替尼）	0.94	0.60~1.48	0.802	1.02	0.42~2.45	0.969

影响因素	HR值	95%CI	P值
性别（男/女）	1.49	0.99~2.24	0.058
PS评分（≥2分/<2分）	0.69	0.39~1.24	0.218
肾上腺转移（有/无）	1.89	1.04~3.41	0.036

影响因素	HR值	95%CI	P值
性别（男/女）	2.22	1.08~4.58	0.031
肝转移（有/无）	1.26	0.40~4.01	0.695
骨转移（有/无）	2.00	0.89~4.48	0.095
肾上腺转移（有/无）	4.87	1.76~13.46	0.002