Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study
Bevacizumab in Patients with Nonsquamous Non-Small Cell Lung Cancer and Asymptomatic, Untreated Brain Metastases (BRAIN): A Nonrandomized, Phase II Study
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DOI：
10.1158/1078-0432.ccr-14-2082
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发表时间：
2015-04-15
影响因子：
11.5
通讯作者：
Soria, Jean-Charles
中科院分区：
文献类型：
--
作者：
Besse, Benjamin;Le Moulec, Sylvestre;Soria, Jean-Charles
目的：第二期前瞻性非对比脑研究(NCT00800202)调查了贝伐单抗对化疗初治或预治疗的非小细胞肺癌(NSCLC)和无症状的脑转移瘤患者的疗效和安全性，以提供这一先前未探索的亚组的数据。实验设计：IV期非小细胞肺癌，东方合作肿瘤组表现状态为0-1，以及未经治疗的无症状脑转移瘤的患者接受一线贝伐单抗(15 mg/kg)加卡铂(曲线下面积x6)和紫杉醇(200 mg/m(2))每3周(B+CP)，或二线贝伐单抗加厄洛替尼(150 mg/d；B+E)。6个月无进展生存期(PFS)是主要终点。结果：在一线B+CP队列(n=67)中，6个月PFS率为56.5%，中位PFS为6.7个月[95%可信区间(CI)5.7~7.1]，中位总生存期(OS)为16.0个月。研究者评估的总有效率(ORR)为62.7%，其中颅内病变为61.2%，颅外病变为64.2%。B+E二线队列的有效率为57.2%，中位PFS为6.3个月(95%CI，3.0~8.4)，中位OS为12.0个月，ORR为12.5%。不良反应与之前的贝伐单抗试验相当。脑部研究显示贝伐单抗联合一线紫杉醇和卡铂治疗非小细胞肺癌和无症状、未经治疗的脑转移瘤的疗效令人鼓舞，安全性可接受。(C)2015年AACR。
Purpose: The phase II prospective, noncomparative BRAIN study (NCT00800202) investigated efficacy and safety of bevacizumab in chemotherapy-naive or pretreated patients with non-small cell lung cancer (NSCLC) and asymptomatic untreated brain metastases to provide data in this previously unexplored subgroup.Experimental Design: Patients with stage IV nonsquamous NSCLC, Eastern Cooperative Oncology Group performance status 0-1, and untreated, asymptomatic brain metastases received first-line bevacizumab (15 mg/kg) plus carboplatin (area under the curve x6) and paclitaxel (200 mg/m(2)) every 3 weeks (B + CP), or second-line bevacizumab plus erlotinib (150 mg/d; B + E). Six-month progression-free survival (PFS) was the primary endpoint. The trial could be stopped if there were more than three (B + CP) or more than two (B + E) intracranial hemorrhages.Results: In first-line B + CP cohort (n = 67), 6-month PFS rate was 56.5% with a median PFS of 6.7 months [95% confidence interval (CI), 5.7-7.1] and median overall survival (OS) of 16.0 months. Investigator-assessed overall response rate (ORR) was 62.7%: 61.2% in intracranial lesions and 64.2% in extracranial lesions. Because of low enrolment (n = 24), efficacy results for the second-line B + E cohort were exploratory only; 6-month PFS rate was 57.2%, median PFS was 6.3 months (95% CI, 3.0-8.4), median OS was 12.0 months, and ORR was 12.5%. Adverse events were comparable with previous trials of bevacizumab. One grade 1 intracranial hemorrhage occurred and resolved without sequelae.Conclusions: The BRAIN study demonstrates encouraging efficacy and acceptable safety of bevacizumab with first-line paclitaxel and carboplatin in patients with NSCLC and asymptomatic, untreated brain metastases. (C)2015 AACR.