BACKGROUND Osimertinib has shown promising activity in patients with leptomeningeal metastases (LM) from epidermal growth factor receptor (EGFR) positive NSCLC at 160 mg once daily (qd) (BLOOM; NCT02228369). We report LM activity with osimertinib 80 mg qd in a retrospective analysis of studies across the AURA program (AURA extension, AURA2, AURA17 and AURA3). METHODS Patients with EGFR T790M-positive advanced NSCLC and progression on prior EGFR-TKI received osimertinib 80 mg qd. Patients with central nervous system (CNS) metastases (including LM) were eligible if lesions were neurologically asymptomatic and stable. Patients with evidence of LM at study entry were retrospectively included for analysis; brain scans were assessed for radiologic LM response by neuroradiological blinded independent central review as per modified Response Assessment in Neuro-Oncology LM criteria. LM objective response rate (ORR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were assessed. A longitudinal analysis was performed to investigate the relationship between baseline non-CNS tumor size changes and LM responses at each visit for AURA LM and BLOOM patients. RESULTS In 22 patients included for analysis, LM ORR was 55% (95% confidence interval [CI]: 32-76). Median LM DoR was not reached (95% CI: 2.8-not calculable [NC]). Median LM PFS and OS were 11.1 months (95% CI: 4.6-NC) and 18.8 months (95% CI: 6.3-NC), respectively. The longitudinal analysis showed similar non-CNS and LM responses between AURA LM and BLOOM patients. CONCLUSION Patients with EGFR T790M-positive NSCLC and radiologically-detected LM derived clinical benefit from osimertinib 80 mg qd.

中文翻译：

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奥希替尼治疗与表皮生长因子受体 T790M 阳性晚期 NSCLC 相关的软脑膜转移患者：AURA LM 分析

背景 奥希替尼在表皮生长因子受体 (EGFR) 阳性 NSCLC 的软脑膜转移 (LM) 患者中显示出有希望的活性，每天 160 毫克 (qd) (BLOOM; NCT02228369)。我们在对整个 AURA 计划（AURA 扩展、AURA2、AURA17 和 AURA3）研究的回顾性分析中报告了 80 毫克 qd 奥希替尼的 LM 活性。方法 EGFR T790M 阳性晚期 NSCLC 和先前 EGFR-TKI 进展的患者接受奥希替尼 80 mg qd。如果病变在神经系统上无症状且稳定，则患有中枢神经系统 (CNS) 转移（包括 LM）的患者符合条件。在研究开始时有 LM 证据的患者被回顾性地纳入分析；根据神经肿瘤学 LM 标准中修改后的反应评估，通过神经放射学盲法独立​​中央审查评估脑部扫描的放射学 LM 反应。评估了 LM 客观缓解率 (ORR)、缓解持续时间 (DoR)、无进展生存期 (PFS) 和总生存期 (OS)。进行纵向分析以研究 AURA LM 和 BLOOM 患者每次就诊时基线非 CNS 肿瘤大小变化与 LM 反应之间的关系。结果 在纳入分析的 22 名患者中，LM ORR 为 55%（95% 置信区间 [CI]：32-76）。未达到中位 LM DoR（95% CI：2.8-不可计算 [NC]）。中位 LM PFS 和 OS 分别为 11.1 个月（95% CI：4.6-NC）和 18.8 个月（95% CI：6.3-NC）。纵向分析显示 AURA LM 和 BLOOM 患者之间的非 CNS 和 LM 反应相似。