Nature Communications ( IF 14.7 ) Pub Date : 2023-02-27 , DOI: 10.1038/s41467-023-35962-x
Juliann Chmielecki , Tony Mok , Yi-Long Wu , Ji-Youn Han , Myung-Ju Ahn , Suresh S. Ramalingam , Thomas John , Isamu Okamoto , James Chih-Hsin Yang , Frances A. Shepherd , Krishna C. Bulusu , Gianluca Laus , Barbara Collins , J. Carl Barrett , Ryan J. Hartmaier , Vassiliki Papadimitrakopoulou
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Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), potently and selectively inhibits EGFR-TKI-sensitizing and EGFR T790M resistance mutations. This analysis evaluates acquired resistance mechanisms to second-line osimertinib (n = 78) in patients with EGFR T790M advanced non-small cell lung cancer (NSCLC) from AURA3 (NCT02151981), a randomized phase 3 study comparing osimertinib with chemotherapy. Plasma samples collected at baseline and disease progression/treatment discontinuation are analyzed using next-generation sequencing. Half (50%) of patients have undetectable plasma EGFR T790M at disease progression and/or treatment discontinuation. Fifteen patients (19%) have >1 resistance-related genomic alteration; MET amplification (14/78, 18%) and EGFR C797X mutation (14/78, 18%).
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AURA3试验分析EGFR突变晚期非小细胞肺癌患者对奥希替尼的获得性耐药机制
奥西替尼是一种表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKI),可有效、选择性地抑制 EGFR-TKI 致敏和EGFR T790M 耐药突变。该分析评估了 AURA3 (NCT02151981) EGFR T790M 晚期非小细胞肺癌 (NSCLC) 患者对二线奥希替尼 (n = 78) 的获得性耐药机制,AURA3 是一项比较奥希替尼与化疗的随机 3 期研究。使用下一代测序分析在基线和疾病进展/治疗停止时收集的血浆样本。一半 (50%) 的患者在疾病进展和/或治疗停止时血浆EGFR T790M 检测不到。 15 名患者 (19%) 存在 >1 耐药性相关基因组改变; MET扩增(14/78,18%)和EGFR C797X 突变(14/78,18%)。