T790M突变与表皮生长因子受体酪氨酸激酶抑制剂继发耐药的相关性

目的:探讨表皮生长因子本酪氨酸激酶抑制剂(EGFR-TKIs)治疗晚期非小细胞肺癌继发耐药的机制。方法:用富集突变PCR(Mutation–enriched PCR)分析46例初治有效且维持≥6个月的晚期非小细胞肺癌患者的外周血和石蜡包埋组织标本的EGFR20外显子T790M突变,分析其与病理特征、疗效、无疾病进展生存时间(PFS)的相关性。结果:46例患者进展期外周血标本中,T790M突变率为39.13%(18/46例),明显高于治疗前标本中5.88%(2/34例)。T790M突变阳性者中位PFS为16.4个月(95%CI:10.83～17.47),野生型患者中位PFS10.2个月(95%CI:10.2～13.47)(P=0.6139)。结论:研究表明T790M突变与EGFR-TKIs继发耐药相关,在非小细胞肺癌患者中存在动态变化,与疗效和生存可能有一定相关性。

T790M mutation and acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor

Objective： To investigate acquired resistance mechanisms of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer （ NSCLC）. Methods： Formalinfixed, paraffin-embedded biopsy tissues and peripheral blood samples were obtained from advanced NSCLC that caused sensitive tumors to become resistant to EGFR-TKIs.EGFR exon20 T790M mutations were detected by Mutation-enriched PCR. Associations between T790M mutation and clinic-pathologic parameters were analyzed. Results： Rates of T790M mutations before and after EGFR-TKIs treatment were 39.13%（18/46）, 5.88%（2/34） ,respectively. The patients with T790M mutations had a longer PFS than those with wild type （ 16.4months vs. 10.2months）（P=0.6139）. Conclusion： T790M mutation is associated with acquired resistance of EGFR-TKIs in NSCLC,and may be relevant to tumor response and clinical outcome in the NSCLC patients.