CNS 反应与奥希替尼在 T790M 阳性晚期 NSCLC 患者中的作用：两项 II 期试验的汇总数据。
CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials.
机构信息
Division of Medical Oncology, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
出版信息
Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.
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.
背景
中枢神经系统（CNS）转移在非小细胞肺癌（NSCLC）患者中很常见。奥希替尼已在 CNS 转移患者中显示出全身疗效，早期临床证据显示其在 CNS 中的疗效。为了进一步评估奥希替尼的活性，我们使用两项 II 期研究（AURA 扩展[NCT01802632]和 AURA2[NCT02094261]）的汇总数据，报告了 CNS 反应的预先指定亚组分析。
患者和方法
先前接受过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，接受奥希替尼 80mg 每日一次（n=411）治疗。有稳定、无症状 CNS 转移且可入组的患者允许接受既往 CNS 治疗。通过盲法独立中枢神经放射学审查（BICR）基线脑部扫描中存在≥1 个可测量的 CNS 病变（根据 RECIST 1.1）的患者被纳入可评估 CNS 反应的患者集（cEFR）。该 CNS 分析的主要终点是 BICR 评估的 CNS 客观缓解率（ORR）；次要终点包括 CNS 缓解持续时间、疾病控制率（DCR）和无进展生存期（PFS）。
结果
基线脑部扫描中 CNS 转移的 128 名患者中，有 50 名患者纳入 cEFR。确认的 CNS ORR 和 DCR 分别为 54%[27/50；95%置信区间（CI）39-68]和 92%（46/50；95% CI 81-98）。无论先前是否对脑部进行过放疗，均观察到 CNS 反应。中枢神经系统缓解持续时间的中位数（22%成熟度）尚未达到（范围，1-15 个月）；9 个月时，估计有 75%（95% CI 53-88）的患者仍处于缓解状态。中枢神经系统 PFS 的中位随访时间为 11 个月；中枢神经系统 PFS 未达到（95% CI，7，无法计算）。在 cEFR 中观察到的安全性特征与总体患者人群一致。
结论
奥希替尼对 CNS 转移具有临床意义的疗效，DCR 高，ORR 令人鼓舞，安全性与先前报道的一致。
临床试验注册
NCT01802632；NCT02094261。
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