Pan Guoqiang, Chen Kaiyan, Yu Xiaoqing, Sheng Jiamin, Fan Yun
The First Clinical Medical College of Wenzhou Medical University, Wenzhou, China.
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
Transl Cancer Res. 2021 Jun;10(6):2895-2905. doi: 10.21037/tcr-21-223.
Osimertinib has been adopted as the standard therapy for T790M-mediated acquired resistance to first-line epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancer (NSCLC). The detection of T790M can be evaluated using different methods. The association between baseline T790M abundance and osimertinib efficacy has not been fully determined.
A total of 144 advanced NSCLC patients positive for T790M, at the time of progression, were retrospectively enrolled in this study. The effect of abundance of T790M mutation on the efficacy of osimertinib was explored.
Among the 144 patients receiving T790M testing, 20 (13.9%) had adopted amplification refractory mutation system (ARMS), 63 (43.8%) adopted droplet digital PCR (ddPCR), and 61 (42.4%) used next-generation sequencing (NGS). The objective response rate was 54.2%, the median progression-free survival was 12.0 months, and the overall survival was 23.0 months for the NSCLC patients treated with osimertinib. Three different technologies to assess T790M mutation (including ARMS, ddPCR, and NGS) could accurately predict the efficacy of osimertinib. There was no significant relationship between the abundance of T790M mutation and the efficacy of osimertinib.
ARMS, ddPCR, and NGS are reliable methods to evaluate EGFR T790M mutation. Osimertinib was equally effective for NSCLC patients with various abundance of T790M mutation.
奥希替尼已被用作非小细胞肺癌（NSCLC）患者中T790M介导的对一线表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）获得性耐药的标准治疗方法。T790M的检测可使用不同方法进行评估。基线T790M丰度与奥希替尼疗效之间的关联尚未完全确定。
本研究回顾性纳入了144例在疾病进展时T790M呈阳性的晚期NSCLC患者。探讨了T790M突变丰度对奥希替尼疗效的影响。
在接受T790M检测的144例患者中，20例（13.9%）采用了扩增阻滞突变系统（ARMS），63例（43.8%）采用了数字液滴PCR（ddPCR），61例（42.4%）采用了二代测序（NGS）。接受奥希替尼治疗的NSCLC患者的客观缓解率为54.2%，中位无进展生存期为12.0个月，总生存期为23.0个月。三种评估T790M突变的不同技术（包括ARMS、ddPCR和NGS）均可准确预测奥希替尼的疗效。T790M突变丰度与奥希替尼疗效之间无显著关系。
ARMS、ddPCR和NGS是评估EGFR T790M突变的可靠方法。奥希替尼对不同T790M突变丰度的NSCLC患者疗效相同。
