GRC OncoTho, Paris-Est, UPEC, Créteil, France; Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France.
Thoracic Oncology Department, CHU Lille, Univ. Lille, Siric OncoLille, Lille, France.
Lung Cancer. 2018 Feb;116:62-66. doi: 10.1016/j.lungcan.2017.12.008. Epub 2017 Dec 14.
Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce.
We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria. Secondary endpoints included intracerebral control rate, intracerebral and general progression-free survival (PFS), overall survival (OS) and tolerance.
Forty-three patients were included. BMs were locally pretreated in 34 (79%) patients and active in 16 (37%) patients. Median follow-up was 5.7 (95% CI: 2.7-8.4) months. IORR and extracerebral response rate were, respectively, 9% (95% CI: 3-23%) and 11% (95% CI: 4-26%). Intracerebral control rate was 51% (95% CI: 37-66%). Median intracerebral and general PFS lasted 3.9 (95% CI: 2.8-11.1) and 2.8 (95% CI: 1.8-4.6) months, respectively. Median OS was 7.5 (95% CI: 5.6-not reached) months. Five neurological adverse events occurred, including 1 grade-4 transient ischemic attack of uncertain imputability and 1 grade-3 neurological deficit; neither required nivolumab discontinuation. Nivolumab intracerebral activity was similar to its reported extracerebral efficacy, with an acceptable safety profile. Prospective and controlled data are needed to determine nivolumab's place in treatment of NSCLC patients with BMs.
尽管纳武利尤单抗已被证实对非小细胞肺癌（NSCLC）有效，但在关键性临床试验中排除了有活动性脑转移（BM）的患者。因此，有关 NSCLC 伴 BM 患者纳武利尤单抗颅内活性和安全性的数据非常有限。
我们对接受纳武利尤单抗治疗的 NSCLC 伴 BM 患者进行了一项回顾性多中心研究。主要终点为根据 RECIST 标准评估的颅内客观缓解率（IORR）。次要终点包括颅内控制率、颅内和总体无进展生存期（PFS）、总生存期（OS）和耐受性。
共纳入 43 例患者。34 例（79%）患者的 BM 经局部预处理，16 例（37%）患者的 BM 处于活跃状态。中位随访时间为 5.7 个月（95%CI：2.7-8.4）。IORR 和颅外缓解率分别为 9%（95%CI：3-23%）和 11%（95%CI：4-26%）。颅内控制率为 51%（95%CI：37-66%）。中位颅内和总体 PFS 分别为 3.9 个月（95%CI：2.8-11.1）和 2.8 个月（95%CI：1.8-4.6）。中位 OS 为 7.5 个月（95%CI：5.6-未达到）。发生了 5 例神经系统不良事件，包括 1 例无法确定关联性的 4 级短暂性脑缺血发作和 1 例 3 级神经功能缺损；均不需要停止纳武利尤单抗治疗。纳武利尤单抗颅内活性与其报道的颅外疗效相似，具有可接受的安全性特征。需要前瞻性和对照数据来确定纳武利尤单抗在治疗 NSCLC 伴 BM 患者中的地位。
