Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial.
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial.
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DOI：
10.1016/s1470-2045(16)30053-5
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Kluger HM
中科院分区：
文献类型：
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作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
靶向PD-1轴的免疫疗法在几种肿瘤类型中具有活性。我们的目的是确定pembrolizumab在未经治疗的脑转移患者中的疗效和安全性。在这里，我们介绍了PD-1抑制剂pembrolizumab在黑色素瘤或非小细胞肺癌（NSCLC）新发或进行性脑转移患者中的II期试验结果。入组了36例患者，18例患有黑色素瘤，18例患有NSCLC。患者至少有一个未经治疗或进行性脑转移，最长直径为5 - 20 mm，无相关神经系统症状或需要皮质类固醇。NSCLC患者的肿瘤组织显示PD-L1表达。患者每两周接受一次帕博利珠单抗10 mg/kg治疗，直至进展，每八周通过改良的RECIST评估一次脑转移缓解。主要终点是脑转移缓解率，分析是在意向治疗基础上进行的。该试验正在进行中，我们在此提供早期分析。该研究注册于clinicaltrials.gov，编号NCT 02085070。黑色素瘤和NSCLC患者脑转移的缓解率分别为22%和33%。反应是持久的，除了一名反应的患者外，所有患者在数据分析时都表现出持续的反应。治疗相关严重和3-4级不良事件罕见，包括转氨酶升高、结肠炎、肺炎、疲乏、内分泌异常和急性肾损伤（各1例患者）。严重神经系统不良事件包括认知功能障碍和癫痫发作（分别为1例和3例患者），由帕博利珠单抗、转移或两者引起。Pembrolizumab在黑色素瘤或NSCLC患者的脑转移中表现出活性，具有可接受的安全性特征，表明全身免疫治疗可能在未经治疗或进行性脑转移患者中发挥作用。默克公司和耶鲁癌症中心。
Immunotherapy targeting the PD-1 axis has activity in several tumor types. We aimed to determine the efficacy and safety of pembrolizumab in patients with untreated brain metastases. Here we present results from a Phase II trial of the PD-1 inhibitor pembrolizumab in patients with new or progressive brain metastases from melanoma or non-small cell lung cancer (NSCLC). Thirty-six patients were enrolled, 18 with melanoma and 18 with NSCLC. Patients had at least one untreated or progressive brain metastasis between 5 and 20 mm in longest diameter without associated neurologic symptoms or the need for corticosteroids. NSCLC patients had tumor tissue demonstrating PD-L1 expression. Patients were treated with pembrolizumab 10 mg/kg every two weeks until progression, and brain metastasis response was assessed every eight weeks by modified RECIST. The primary endpoint was brain metastasis response rate and the analysis was performed on an intent-to-treat basis. The trial is ongoing and here we present an early analysis. The study is registered with clinicaltrials.gov, number NCT02085070. Brain metastasis response rate was 22% and 33% among patients with melanoma and NSCLC, respectively. Responses were durable, with all but one patient who responded demonstrating an ongoing response at the time of data analysis. Treatment-related serious and grade 3–4 adverse events were rare and included transaminitis, colitis, pneumonitis, fatigue, endocrine abnormalities, and acute kidney injury (1 patient each). Serious neurological adverse events included cognitive dysfunction and seizures (1 and 3 patients, respectively), due to pembrolizumab, metastases or both. Pembrolizumab demonstrates activity in brain metastases in patients with melanoma or NSCLC with an acceptable safety profile, indicating that there may be a role for systemic immunotherapy in patients with untreated or progressive brain metastases. Merck and the Yale Cancer Center.