John Thomas, Bowden Jeffrey J, Clarke Stephen, Fox Stephen B, Garrett Kerryn, Horwood Keith, Karapetis Christos S
Austin Health, Heidelberg, Victoria, Australia.
Flinders Medical Centre and Flinders University, South Australia, Australia.
Asia Pac J Clin Oncol. 2017 Aug;13(4):296-303. doi: 10.1111/ajco.12699. Epub 2017 Jul 12.
First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as first-line therapy in patients with non-small cell lung cancer (NSCLC) harboring a sensitizing mutation in the EGFR gene. Unfortunately, resistance to these therapies often occurs within 10 months of commencing treatment and is mostly commonly due to the development of the EGFR T790M mutation. Treatment with the third-generation EGFR TKI, osimertinib can prolong progression free survival in patients with the T790M mutation, so it is important to determine the resistance mechanism in order to plan ongoing therapeutic strategies. Here we review the evidence and make recommendations for the timing of T790M mutation testing, the most appropriate specimens to test and the available testing methods in patients progressing during treatment with first line EGFR TKIs for NSCLC.
第一代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)被用作一线治疗,用于治疗表皮生长因子受体(EGFR)基因存在敏感突变的非小细胞肺癌(NSCLC)患者。不幸的是,这些治疗方法的耐药性通常在开始治疗后的10个月内出现,最常见的原因是EGFR T790M突变的发生。使用第三代EGFR TKI奥希替尼进行治疗可延长T790M突变患者的无进展生存期,因此确定耐药机制对于规划后续治疗策略很重要。在此,我们回顾相关证据,并就T790M突变检测的时机、最合适的检测标本以及在一线EGFR TKIs治疗NSCLC期间病情进展的患者中可用的检测方法提出建议。