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阿法替尼用于一线治疗携带常见表皮生长因子受体(EGFR)突变的非小细胞肺癌(NSCLC):基于LUX-Lung 7研究初步结果的新见解?

Afatinib in first-line setting for NSCLC harbouring common EGFR mutations: new light after the preliminary results of LUX-Lung 7?

作者信息

Passaro Antonio, Pochesci Alessia, Spitaleri Gianluca, Catania Chiara, Noberasco Cristina, Del Signore Ester, de Marinis Filippo

机构信息

Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.

出版信息

J Thorac Dis. 2016 Mar;8(3):E217-20. doi: 10.21037/jtd.2016.02.21.

Abstract

The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) changed dramatically the history of non-small cell lung cancer (NSCLC) harboring EGFR sensitive mutations. Several randomized prospective trials confirmed the superiority of these target agents about survival and response rate when comparing with platinum-based chemotherapy. Knowledge about EGFR mutations increased gradually during the development of target agents and different clinical trials. EGFR mutations cannot be considered all equal, but different entities should be considered in our clinical practice: exon 19 deletions, exon 21 mutation (L858R) and uncommon mutation (exon 20, exon 18 and double mutation). Nowadays, we dispose of three different EGFR TKIs (afatinib, erlotinib and gefitinib) approved for the treatment for first-line treatment of patients di NSCLC carrying EGFR, that was compared only by indirect analysis, producing data not always clear and convincing. This research highlight is an overview of data about EGFR TKIs in first-line setting, focusing on differences about exon 19 deletions and L585R mutation in patients treated with different TKIs. In addition, we report the preliminary results of the first head-to-head randomized clinical trial between two different EGFR TKIs, the LUX-Lung 7 (LL7) that compared afatinib and gefitinib showing interesting results.

摘要

表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)的发展极大地改变了携带EGFR敏感突变的非小细胞肺癌(NSCLC)的治疗史。多项随机前瞻性试验证实,与铂类化疗相比,这些靶向药物在生存率和缓解率方面具有优势。在靶向药物和不同临床试验的发展过程中,人们对EGFR突变的认识逐渐增加。不能认为所有的EGFR突变都是相同的,在我们的临床实践中应考虑不同的类型:外显子19缺失、外显子21突变(L858R)和罕见突变(外显子20、外显子18和双突变)。如今,我们有三种不同的EGFR TKIs(阿法替尼、厄洛替尼和吉非替尼)被批准用于一线治疗携带EGFR的NSCLC患者,此前仅通过间接分析进行比较,得出的数据并不总是清晰且有说服力。本研究重点概述了一线治疗中EGFR TKIs的数据,重点关注使用不同TKIs治疗的患者中外显子19缺失和L585R突变的差异。此外,我们报告了两项不同EGFR TKIs之间首次头对头随机临床试验——LUX-Lung 7(LL7)的初步结果,该试验比较了阿法替尼和吉非替尼,结果令人关注。

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