Purpose The AURA study ( ClinicalTrials.gov identifier: NCT01802632) included two cohorts of treatment-naïve patients to examine clinical activity and safety of osimertinib (an epidermal growth factor receptor [EGFR] -tyrosine kinase inhibitor selective for EGFR-tyrosine kinase inhibitor sensitizing [ EGFRm] and EGFR T790M resistance mutations) as first-line treatment of EGFR-mutated advanced non-small-cell lung cancer (NSCLC). Patients and Methods Sixty treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily (30 patients per cohort). End points included investigator-assessed objective response rate (ORR), progression-free survival (PFS), and safety evaluation. Plasma samples were collected at or after patients experienced disease progression, as defined by Response Evaluation Criteria in Solid Tumors (RECIST), to investigate osimertinib resistance mechanisms. Results At data cutoff (November 1, 2016), median follow-up was 19.1 months. Overall ORR was 67% (95% CI, 47% to 83%) in the 80-mg group, 87% (95% CI, 69% to 96%) in the 160-mg group, and 77% (95% CI, 64% to 87%) across doses. Median PFS time was 22.1 months (95% CI, 13.7 to 30.2 months) in the 80-mg group, 19.3 months (95% CI, 13.7 to 26.0 months) in the 160-mg group, and 20.5 months (95% CI, 15.0 to 26.1 months) across doses. Of 38 patients with postprogression plasma samples, 50% had no detectable circulating tumor DNA. Nine of 19 patients had putative resistance mechanisms, including amplification of MET (n = 1); amplification of EGFR and KRAS (n = 1); MEK1, KRAS, or PIK3CA mutation (n = 1 each); EGFR C797S mutation (n = 2); JAK2 mutation (n = 1); and HER2 exon 20 insertion (n = 1). Acquired EGFR T790M was not detected. Conclusion Osimertinib demonstrated a robust ORR and prolonged PFS in treatment-naïve patients with EGFRm advanced NSCLC. There was no evidence of acquired EGFR T790M mutation in postprogression plasma samples.

中文翻译：

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奥希替尼作为 EGFR 突变阳性晚期非小细胞肺癌的一线治疗

目的 AURA 研究（ClinicalTrials.gov 标识符：NCT01802632）包括两组初治患者，以检查 osimertinib（一种表皮生长因子受体 [EGFR]-酪氨酸激酶抑制剂，对 EGFR-酪氨酸激酶抑制剂致敏 [ EGFRm] 和 EGFR T790M 耐药突变）作为 EGFR 突变的晚期非小细胞肺癌（NSCLC）的一线治疗。患者和方法 60 名未经治疗的局部晚期或转移性 EGFRm NSCLC 患者每天接受一次 80 或 160 毫克的奥希替尼（每组 30 名患者）。终点包括研究者评估的客观缓解率 (ORR)、无进展生存期 (PFS) 和安全性评估。在患者出现疾病进展时或之后收集血浆样本，根据实体瘤疗效评估标准 (RECIST) 的定义，研究奥希替尼耐药机制。结果 在数据截止时（2016 年 11 月 1 日），中位随访时间为 19.1 个月。80 mg 组的总体 ORR 为 67%（95% CI，47% 至 83%），160 mg 组为 87%（95% CI，69% 至 96%），77%（95% CI） , 64% 到 87%) 跨剂量。80 毫克组的中位 PFS 时间为 22.1 个月（95% CI，13.7 至 30.2 个月），160 毫克组为 19.3 个月（95% CI，13.7 至 26.0 个月）和 20.5 个月（95% CI， 15.0 至 26.1 个月）跨剂量。在有进展后血浆样本的 38 名患者中，50% 没有可检测到的循环肿瘤 DNA。19 名患者中有 9 名具有推定的耐药机制，包括 MET 扩增（n = 1）；EGFR 和 KRAS 扩增（n = 1）；MEK1、KRAS 或 PIK3CA 突变（每个 n = 1）；EGFR C797S 突变（n = 2）；JAK2 突变（n = 1）；和 HER2 外显子 20 插入（n = 1）。未检测到获得性 EGFR T790M。结论 奥希替尼在初治 EGFRm 晚期 NSCLC 患者中表现出稳健的 ORR 和延长的 PFS。在进展后血浆样本中没有获得性 EGFR T790M 突变的证据。