Background: Osimertinib was first approved for the treatment of non-small cell lung cancer (NSCLC) in patients who have developed the epidermal growth factor receptor (EGFR) T790M mutation after treatment with EGFR tyrosine kinase inhibitors (TKIs). We routinely evaluated the plasma of NSCLC patients with the T790M mutation to more rapidly detect an increase in disease activity and resistance to treatment. Methods: Eligible patients received osimertinib after resistance to the first- or second-generation of EGFR-TKIs in NSCLC harboring T790M mutation detectable in tumor tissue or plasma. Plasma samples were collected every 8 weeks during osimertinib treatment. The plasma analysis was performed using an improved PNA-LNA PCR clamp method. We tested samples for a resistance mechanism, including EGFR-activating, T790M, and C797S mutations, and assessed the association between the mutations and osimertinib treatment. Results: Of the 60 patients enrolled in the study, 58 were eligible for this analysis. In plasma collected before osimertinib treatment, activating mutations were detected in 47 of 58 patients (81.0%) and T790M was detected in 44 patients (75.9%). Activating mutations were cleared in 60.9% (28/46) and T790M was cleared in 93.0% (40/43). Of these, 71.4% (20/28) of activating mutations and 87.5% (35/40) of T790M mutation were cleared within 8 weeks of treatment. The total response rate (RR) was 53.4% (31/58). The median duration of treatment was 259 days, with a trend toward longer treatment duration in patients who experienced the clearance of activating mutations with osimertinib. At the time of disease progression during osimertinib treatment, C797S was detected in 3 of 37 patients (8.1%). Conclusion: Plasma EGFR mutation analysis was effective in predicting the effect of osimertinib treatment.
背景：奥希替尼最初被批准用于治疗经表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）治疗后出现EGFR T790M突变的非小细胞肺癌（NSCLC）患者。我们常规评估携带T790M突变的NSCLC患者的血浆，以更迅速地检测疾病活动性增加和治疗耐药性。方法：符合条件的患者在出现对第一代或第二代EGFR-TKIs耐药后，接受奥希替尼治疗，这些患者的肿瘤组织或血浆中可检测到T790M突变。在奥希替尼治疗期间，每8周收集一次血浆样本。血浆分析采用改进的PNA-LNA PCR clamp方法进行。我们检测了样本的耐药机制，包括EGFR激活突变、T790M和C797S突变，并评估了这些突变与奥希替尼治疗之间的关联。结果：在研究纳入的60名患者中，58名符合本次分析条件。在奥希替尼治疗前收集的血浆中，58名患者中有47名（81.0%）检测到激活突变，44名患者（75.9%）检测到T790M突变。激活突变在60.9%（28/46）的患者中被清除，T790M突变在93.0%（40/43）的患者中被清除。其中，71.4%（20/28）的激活突变和87.5%（35/40）的T790M突变在治疗8周内被清除。总缓解率（RR）为53.4%（31/58）。中位治疗持续时间为259天，在奥希替尼治疗期间激活突变被清除的患者中，治疗持续时间有延长的趋势。在奥希替尼治疗期间疾病进展时，37名患者中有3名（8.1%）检测到C797S突变。结论：血浆EGFR突变分析可有效预测奥希替尼的治疗效果。
肿瘤(癌症)患者之家