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吉非替尼或厄洛替尼用于既往治疗过的非小细胞肺癌患者:台湾的一项队列研究

Gefitinib or erlotinib in previously treated non-small-cell lung cancer patients: a cohort study in Taiwan.

作者信息

Chang Chia-Hao, Lee Chih-Hsin, Ko Jen-Chung, Chang Lih-Yu, Lee Ming-Chia, Wang Jann-Yuan, Yu Chong-Jen

机构信息

Department of Internal Medicine, National Taiwan University Hospital, Hsinchu Branch, Hsin Chu City, Taiwan.

Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.

出版信息

Cancer Med. 2017 Jul;6(7):1563-1572. doi: 10.1002/cam4.1121. Epub 2017 Jun 22.

Abstract

Among treatment modalities for lung cancer, the most promising therapy is the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Both erlotinib and gefitinib, the two first-generation EGFR-TKIs, exhibit significant clinical responses for patients with lung adenocarcinoma. However, few studies have compared the effects of these two drugs, and results have been inconclusive because of the small sample sizes in these studies. Therefore, this study was conducted to investigate this issue. This retrospective nationwide cohort study enrolled NSCLC patients who received EGFR-TKIs after previous chemotherapy in Taiwan between 1996 and 2010 from the National Health Insurance Research Database. Clinical response and survival after receiving erlotinib and gefitinib were compared using logistic and Cox regression analyses, respectively. Inverse propensity score weighting and a sensitivity analysis in the EGFR-TKI responder (clinical improvement by taking EGFR-TKIs for 90 days), adherent patients (receiving EGFR-TKI on a daily basis), adenocarcinoma, and adenocarcinoma with second-line TKIs subgroup were performed for bias adjustment. A total of 7222 patients, including 4592 (63.6%) who received gefitinib, were identified. In the survival analysis, erlotinib was associated with a decline in 1-year progression-free survival (PFS) (hazard ratio, HR: 1.15 [1.09-1.21]) and overall survival (OS) (HR: 1.10 [1.03-1.18]). The effects of various TKIs were consistent in the 4939 EGFR-TKI responders, adherent subgroup, adenocarcinoma subgroup, and adenocarcinoma with second-line TKIs subgroup. In previously treated EGFT-TKI-naive NSCLC patients, those receiving gefitinib exhibited a longer PFS and OS than those receiving erlotinib. Additional large-scale randomized controlled trials are warranted to confirm this finding.

摘要

在肺癌的治疗方式中,最有前景的疗法是使用表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)。厄洛替尼和吉非替尼这两种第一代EGFR-TKIs,对肺腺癌患者均显示出显著的临床疗效。然而,很少有研究比较这两种药物的效果,且由于这些研究的样本量较小,结果尚无定论。因此,开展本研究以调查该问题。这项全国性回顾性队列研究纳入了1996年至2010年期间在台湾地区接受过先前化疗后又接受EGFR-TKIs治疗的非小细胞肺癌(NSCLC)患者,数据来自国民健康保险研究数据库。分别使用逻辑回归和Cox回归分析比较接受厄洛替尼和吉非替尼后的临床疗效和生存率。对EGFR-TKI反应者(服用EGFR-TKIs 90天临床改善)、依从性患者(每日接受EGFR-TKI治疗)、腺癌以及二线TKIs治疗的腺癌亚组进行逆倾向评分加权和敏感性分析以调整偏倚。共识别出7222例患者,其中4592例(63.6%)接受了吉非替尼治疗。在生存分析中,厄洛替尼与1年无进展生存期(PFS)下降相关(风险比,HR:1.15 [1.09 - 1.21])以及总生存期(OS)下降相关(HR:1.10 [1.03 - 1.18])。在4939例EGFR-TKI反应者、依从性子组、腺癌亚组以及二线TKIs治疗的腺癌亚组中,各种TKIs的效果一致。在先前接受过治疗的初治EGFT-TKI的NSCLC患者中,接受吉非替尼治疗的患者比接受厄洛替尼治疗的患者具有更长的PFS和OS。需要更多大规模随机对照试验来证实这一发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34d0/5504326/e6edf42fe78e/CAM4-6-1563-g001.jpg

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