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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 Sensitive mutations in the epidermal growth factor receptor (EGFR) are effective predictors of EGFR tyrosine kinase inhibitors (TKIs). 85% -90% of sensitivity mutations occurred in 19 deletion mutation and 21 exon L858R mutation. The objective response rate (ORR) and progression-free survival (PFS) of EGFR-TKIs in patients with common EGFR-sensitive mutations were significantly prolonged, reaching 70% -80% and 9 months -14 months. However, the effect of EGFR-TKIs on uncommon mutations of EGFR is unclear. The purpose of this study was to investigate the clinicopathological features of rare EGFR mutations and the long-term and long-term effects of EGFR-TKIs. Methods The clinical data of 24 patients with rare EGFR mutations collected from April 2010 to April 2015 in Peking University Cancer Hospital were collected. The clinicopathological features of rare EGFR mutations and the relationship between them and the efficacy of TKIs and PFS were analyzed. Results Of 24 patients with rare mutations, 15 were single mutations and 9 were double mutations. Of the 15 single mutations, the mutations of S768I, L861Q, and exon 20 were inserted, and G719X was 4, 4, 3 and 2, respectively. The double mutation in the merger with S768I G719X the most common (3/9). Among the 13 patients treated with EGFR-TKIs, the ORR was 46.1% (6/13), the disease control rate (DCR) was 76.9% (10/13) and the median PFS was 7.4 months. Conclusion As a special type of EGFR mutation, the rare EGFR mutation has a sensitivity between EGFR-sensitive mutations and EGFR wild type for one generation of EGFR-TKIs. Second-generation EGFRTKIs may be more suitable for the treatment of rare mutations in EGFR relative to first-generation EGFR-TKIs. .