NSCLC携带EGFR少见突变分析及EGFR-TKIs疗效初步观察

Effectiveness of Tyrosine Kinase Inhibitors on Uncommon Epidermal Growth Factor Receptor Mutations in Non-small Cell Lung Cancer

背景与目的表皮生长因子受体(epidermal growth factor receptor,EGFR)敏感性突变是EGFR酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)的有效预测因子。85%-90%敏感性突变发生于19缺失突变及21外显子L858R突变。常见EGFR敏感性突变患者EGFR-TKIs治疗的客观缓解率(objective response rate,ORR)和无病进展生存时间(progression-free survival,PFS)显著延长,可分别达70%-80%和9个月-14个月。但EGFR-TKIs对于EGFR少见突变(uncommon mutations)的疗效尚不明确。本研究旨在探讨EGFR少见突变的临床病理特征及EGFR-TKIs治疗的远近期疗效。方法收集2010年4月-2015年4月北京大学肿瘤医院胸部肿瘤内科24例少见EGFR突变患者的临床资料,分析少见EGFR突变的临床病理特征及与TKIs疗效及PFS之间的关系。结果 24例携带少见突变的患者中,单突变者15例,双突变者9例。15例单突变中,S768I、L861Q、20外显子插入突变、G719X分别为4例、4例、3例、2例。双突变中以S768I合并G719X最为常见(3/9)。在接受EGFR-TKIs治疗的13例患者中,ORR为46.1%(6/13),疾病控制率(disease control rate,DCR)为76.9%(10/13),中位PFS为7.4个月。结论作为特殊类型的EGFR突变,EGFR少见突变对于一代EGFR-TKIs的敏感性介于EGFR敏感性突变和EGFR野生型之间。相对于一代EGFR-TKIs而言,二代EGFRTKIs可能更适用于EGFR少见突变的治疗。。

Background and objective Epidermal growth factor receptor (EGFR) mutations occur more frequently in non-small cell lung cancer (NSCLC) of women, never smokers, Asian population and those with adenocarcinoma. Short in-frame deletion in exon 19 and L858R substitution are the most common mutations, which are closely associated with EGFR tyrosine kinase inhibitors (TKIs) treatment response. However, the therapeutic effects of EGFR-TKIs on NSCLC with uncom-monEGFR mutation subtypes remain unclear. hTe aim of this study is to investigate the clinicopathologic feature of uncom-monEGFR mutations and the outcomes of these patients.Methods Twenty-four patients that harbored uncommonEGFR mutations were included in this study. Clinicopathologic features of uncommonEGFR mutations and the outcomes of these patients were analyzed.Results Of the 24 patients, 13 received EGFR-TKIs treatment. hTe response rate of EGFR-TKIs treat-ment was 46.1%, and the median progression-free survival (PFS) was 7.4 months. Mutations on S768I and L861Q composed a major part (8 of 24) of uncommon mutations.Conclusions UncommonEGFR mutations constituted a unique part of the whole group ofEGFR mutations. hTeir composition and sensitivity to EGFR-TKIs were heterogeneous, which requires further assessment in a prospective study.