Watanabe Kana, Saito Ryota, Miyauchi Eisaku, Nagashima Hiromi, Nakamura Atsushi, Sugawara Shunichi, Tanaka Nobuyuki, Terasaki Hiroshi, Fukuhara Tatsuro, Maemondo Makoto
Department of Respiratory Medicine, Miyagi Cancer Center, Natori 981-1293, Japan.
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Cancers (Basel). 2023 Aug 24;15(17):4231. doi: 10.3390/cancers15174231.
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.
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.
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%).
Plasma EGFR mutation analysis was effective in predicting the effect of osimertinib treatment.
奥希替尼最初被批准用于治疗在接受表皮生长因子受体（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T790M突变的NSCLC患者的血浆，以更快地检测疾病活动增加和对治疗的耐药性。
符合条件的患者在对第一代或第二代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周采集一次血浆样本。使用改进的肽核酸-锁核酸PCR钳夹法进行血浆分析。我们检测样本的耐药机制，包括EGFR激活、T790M和C797S突变，并评估突变与奥希替尼治疗之间的关联。
在纳入研究的60例患者中，58例符合本分析条件。在奥希替尼治疗前采集的血浆中，58例患者中有47例（81.0%）检测到激活突变，44例患者（75.9%）检测到T790M。60.9%（28/46）的激活突变和93.0%（40/43）的T790M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，在接受奥希替尼治疗后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例患者中有三例（8.1%）检测到C797S。
血浆EGFR突变分析可有效预测奥希替尼的治疗效果。
