CLIN CANCER RES:Osimertinib治疗EGFR突变非小细胞肺癌的耐药机制

2018-12-21 MedSci MedSci原创

Osimertinib最初被批准用于治疗T790M阳性非小细胞肺癌(NSCLC),最近用于EGFR -mutant NSCLC的一线治疗。但是osimertinib的耐药机制尚不完全清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

Osimertinib最初被批准用于治疗T790M阳性非小细胞肺癌NSCLC),最近用于EGFR -mutant NSCLC的一线治疗。但是osimertinib的耐药机制尚不完全清楚。CLIN CANCER RES近期发表了一篇文章研究这一问题。

作者使用了来自德克萨斯大学MD Anderso数据库的队列,收集了接受osimertinib治疗的患者的临床数据。在一部分患者疾病进展时进行分子谱分析。在接受osimertinib治疗的118名患者中,42名患者在进展时进行了分子谱分析。21例(50%)患者中仍存在T790M,21例(50%)患者丢失。EGFR C797和L792(26%)突变是最常见的耐药机制,仅在存在T790M的病例中观察到。MET扩增是第二常见的改变(14%)。在22个基因/通路中观察到复发突变,包括PIK3CA,FGFR和RET。临床前研究证实MET,PIK3CA和上皮-间质转化是潜在的耐药性驱动因子。细胞周期基因的改变与较短的中位无进展生存期相关。在76名出现进展患者中,持续使用osimertinib治疗47例,中位PFS(PFS2)为12.6个月; 21例患者接受局部巩固放疗,中位PFS为15.5个月。与停药相比,进展后osimertinib持续治疗与较长的总生存期相关。

文章最后认为,Osimertinib耐药与多种基因有关,主要是EGFR非依赖性基因组改变。在疾病进展后,单独或与放疗联合继续使用osimertinib可以提供延长患者临床获益。

原始出处:

Xiuning Le, Sonam Puri, et al. Landscape of EGFR-Dependent and -Independent Resistance Mechanisms to Osimertinib and Continuation Therapy Beyond Progression in EGFR-Mutant NSCLC. CLIN CANCER RES. December 2018 doi: 10.1158/1078-0432.CCR-18-1542

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