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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。
Objective: To investigate the mechanism of epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of secondary non-small cell lung cancer. Methods: Mutation-enriched PCR was used to analyze EGFR20 exon T790M mutation in peripheral blood and paraffin-embedded tissues from 46 patients with newly diagnosed and advanced non-small cell lung cancer who were maintained for 6 months. Its correlation with pathological features, curative effect, and progression-free survival (PFS). Results: The T790M mutation rate was 39.13% (18/46) in the 46 cases of advanced peripheral blood samples, which was significantly higher than 5.88% (2/34 cases) before treatment. Median PFS was 16.4 months (95% CI: 10.83-17.47) for patients with T790M mutation positive and 10.2 months (95% CI: 10.2-13.47) for patients with wild-type PFS (P = 0.6139). Conclusion: The study shows that the T790M mutation is associated with the secondary drug resistance of EGFR-TKIs, which has a dynamic change in patients with non-small cell lung cancer and may be related to efficacy and survival.