Background Central nervous system (CNS) metastases are common in patients with non-small-cell lung cancer (NSCLC). Osimertinib has shown systemic efficacy in patients with CNS metastases, and early clinical evidence shows efficacy in the CNS. To evaluate osimertinib activity further, we present a pre-specified subgroup analysis of CNS response using pooled data from two phase II studies: AURA extension (NCT01802632) and AURA2 (NCT02094261). Patients and methods Patients with T790M-positive advanced NSCLC, who had progressed following prior epidermal growth factor receptor-tyrosine kinase inhibitor treatment, received osimertinib 80 mg od (n = 411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment; prior CNS treatment was allowed. Patients with ≥1 measurable CNS lesion (per RECIST 1.1) on baseline brain scan by blinded independent central neuroradiology review (BICR) were included in the evaluable for CNS response set (cEFR). The primary outcome for this CNS analysis was CNS objective response rate (ORR) by BICR; secondary outcomes included CNS duration of response, disease control rate (DCR) and progression-free survival (PFS). Results Of 128 patients with CNS metastases on baseline brain scans, 50 were included in the cEFR. Confirmed CNS ORR and DCR were 54% [27/50; 95% confidence interval (CI) 39-68] and 92% (46/50; 95% CI 81-98), respectively. CNS response was observed regardless of prior radiotherapy to the brain. Median CNS duration of response (22% maturity) was not reached (range, 1-15 months); at 9 months, 75% (95% CI 53-88) of patients were estimated to remain in response. Median follow-up for CNS PFS was 11 months; median CNS PFS was not reached (95% CI, 7, not calculable). The safety profile observed in the cEFR was consistent with the overall patient population. Conclusions Osimertinib demonstrated clinically meaningful efficacy against CNS metastases, with a high DCR, encouraging ORR, and safety profile consistent with that reported previously. ClinicalTrials.gov number NCT01802632; NCT02094261.

中文翻译：

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T790M阳性晚期NSCLC患者中枢神经系统对osimertinib的反应：来自两项II期临床试验的汇总数据。

背景非小细胞肺癌（NSCLC）患者常见中枢神经系统（CNS）转移。奥西替尼已显示出对中枢神经系统转移患者的全身疗效，而早期的临床证据表明，其在中枢神经系统中具有疗效。为了进一步评估osimertinib的活性，我们使用来自两项II期研究的汇总数据（AURA扩展（NCT01802632）和AURA2（NCT02094261））对CNS反应进行了预先指定的亚组分析。患者和方法经过先前的表皮生长因子受体-酪氨酸激酶抑制剂治疗后进展的T790M阳性晚期NSCLC患者接受了奥西替尼80 mg od（n = 411）治疗。稳定，无症状的CNS转移的患者符合入组条件；允许先前的中枢神经系统治疗。可测量的CNS病变≥1的患者（根据RECIST 1）。1）在基线基础上，通过双盲独立中枢神经放射学审查（BICR）进行的脑部扫描包括在可评估中枢神经系统反应集（cEFR）中。这项CNS分析的主要结果是BICR得出的CNS客观反应率（ORR）。次要结果包括中枢神经系统反应持续时间，疾病控制率（DCR）和无进展生存期（PFS）。结果在基线脑部扫描中有128例CNS转移患者中，有50例被包括在cEFR中。确认的CNS ORR和DCR为54％[27/50; 95％置信区间（CI）39-68]和92％（46/50; 95％CI 81-98）。无论是否对脑进行放射治疗，都可以观察到CNS反应。中枢神经系统反应持续时间中位数（成熟度为22％）尚未达到（范围1-15个月）；在9个月时，估计仍有75％（95％CI 53-88）的患者仍然有反应。中枢神经系统PFS的中位随访时间为11个月；中位数CNS PFS未达到（95％CI，7，不可计算）。在cEFR中观察到的安全性与患者总数一致。结论Osimertinib具有抗CNS转移的临床意义，具有高DCR，令人鼓舞的ORR，并且安全性与先前报道的相符。ClinicalTrials.gov编号NCT01802632；NCT02094261。