NSCLC携带EGFR少见突变分析及EGFR-TKIs疗效初步观察 Translated title: Effectiveness of Tyrosine Kinase Inhibitors on Uncommon Epidermal Growth Factor Receptor Mutations in Non-small Cell Lung Cancer

Abstract

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EGFR-TKIs可能更适用于 EGFR少见突变的治疗。。

Translated abstract

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 uncommon EGFR mutation subtypes remain unclear. The aim of this study is to investigate the clinicopathologic feature of uncommon EGFR mutations and the outcomes of these patients.

Methods

Twenty-four patients that harbored uncommon EGFR mutations were included in this study. Clinicopathologic features of uncommon EGFR mutations and the outcomes of these patients were analyzed.

Results

Of the 24 patients, 13 received EGFR-TKIs treatment. The response rate of EGFR-TKIs treatment 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

Uncommon EGFR mutations constituted a unique part of the whole group of EGFR mutations. Their composition and sensitivity to EGFR-TKIs were heterogeneous, which requires further assessment in a prospective study.