Rossi Sabrina, D'Argento Ettore, Basso Michele, Strippoli Antonia, Dadduzio Vincenzo, Cerchiaro Eleonora, Martini Maurizio, Cassano Alessandra, Barone Carlo
Department of Medical Oncology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
Department of Pathology, Catholic University of Sacred Heart, Largo A. Gemelli, 8, 00168, Rome, Italy.
Mol Diagn Ther. 2016 Feb;20(1):55-63. doi: 10.1007/s40291-015-0176-x.
Mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predict longer overall survival (OS) and response to EGFR tyrosine kinase inhibitors (TKIs). The clinical relevance of different mutations in terms of response to TKIs and prognosis is still unclear.
The aims of the present study were to assess the relationship between mutations in exon 18, 19 and 21 in patients treated with TKIs and their clinical outcomes, and evaluate the role of specific point mutations.
We included in this analysis 55 patients with metastatic NSCLC and mutations in exon 18, 19 and 21, treated in our center between 2004 and 2014. All patients received treatment with TKIs in first and/or subsequent lines. Endpoints analyzed were OS (primary) and time to progression (TTP) (secondary), according to exon mutations and specific point mutations.
A strong negative prognostic association for OS (p = 0.02) and TTP (p = 0.03) was found for exon 18 mutations compared with exon 19 deletions . A trend toward a longer median OS was observed in exon 19 deletions versus exon 21 point mutations (+6.6 months), although more exon 19-mutated patients had brain metastases at diagnosis. Comparing each mutation, p.E746_A750del and p.E746_T751del of exon 19 and p.L858R mutation of exon 21, a trend toward improved OS in p.E746_A750del was found.
In this analysis, exon 19 deletions were associated with better outcomes, despite a higher percentage of brain metastases in this group. The prognostic relevance of p.E746_A750del requires further studies.
非小细胞肺癌（NSCLC）中表皮生长因子受体（EGFR）突变预示着更长的总生存期（OS）以及对EGFR酪氨酸激酶抑制剂（TKIs）的反应。不同突变在TKIs反应和预后方面的临床相关性仍不明确。
本研究的目的是评估接受TKIs治疗的患者外显子18、19和21突变与其临床结局之间的关系，并评估特定点突变的作用。
我们纳入了2004年至2014年间在本中心接受治疗的55例转移性NSCLC且外显子18、19和21有突变的患者。所有患者在一线和/或后续治疗中接受了TKIs治疗。根据外显子突变和特定点突变分析的终点为OS（主要终点）和疾病进展时间（TTP）（次要终点）。
与外显子19缺失相比，外显子18突变的患者在OS（p = 0.02）和TTP（p = 0.03）方面存在强烈的负面预后关联。尽管更多外显子19突变的患者在诊断时已有脑转移，但外显子19缺失的患者中位OS有长于外显子21点突变患者的趋势（长6.6个月）。比较每种突变，外显子19的p.E746_A750del和p.E746_T751del以及外显子21的p.L858R突变，发现p.E746_A750del有OS改善的趋势。
在本分析中，外显子19缺失与更好的结局相关，尽管该组脑转移的比例更高。p.E746_A750del的预后相关性需要进一步研究。
