Efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma: a retrospective analysis
Efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma: a retrospective analysis
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DOI：
10.21037/jtd.2019.10.49
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发表时间：
2019-11-01
影响因子：
2.5
通讯作者：
Liang, Xiaohua
中科院分区：
文献类型：
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作者：
Zhan, Qiong;Miao, Feng;Liang, Xiaohua
目前，肺腺癌症状性脑转移的治疗仍然很困难。贝伐单抗联合化疗是肺腺癌的标准治疗方法之一。本研究旨在观察贝伐单抗联合化疗治疗不宜局部治疗的肺腺癌症状性脑转移的疗效和安全性，并探讨基线血清血管内皮生长因子(VEGF)对治疗的预测价值。方法：对2015年1月至2017年7月连续14例接受贝伐单抗联合化疗的肺腺癌脑转移患者进行回顾性分析，以确定其疗效和毒性。生存曲线估计采用Kaplan-Meier法，单因素和多因素分析采用Cox比例风险模型。主要终点为客观缓解率(ORR)和颅内缓解率(IORR)。次要终点为无进展生存期(PFS)、颅内无进展生存期(IPFS)、总生存期(OS)和疾病控制率(DCR)。总的ORR为25%(3/12)，其中脑部病变的ORR为33.3%(4/12)。DCR为75%(9/12)。中位OS为18.3个月，中位PFS为6.7个月，中位IPFS为12个月。贝伐单抗治疗2周期后，10例中枢神经系统(CNS)症状改善，症状控制率83.3%(10/12)。头部MRI显示6例患者脑内水肿明显减轻，地塞米松使用量减少。多因素相关分析显示，高水平血管内皮生长因子水平与IPFS显著相关(P=0.023)。贝伐单抗最常见的不良反应是白细胞减少[5(35.7%)]、乏力[3(21.4%)]、血小板减少[3(21.4%)]、贫血[2(14.3%)]，且以I、II度为主。结论：贝伐单抗联合化疗能有效控制脑转移癌患者的颅内病变，缓解症状，提高患者的生活质量和生存质量。血清基线血管内皮生长因子可能是贝伐单抗联合化疗治疗肺腺癌脑转移疗效的预测指标。
Baokground: Currently, the treatment of symptomatic brain metastases from lung adenocarcinoma has remained difficult. Bevacizumab combined with chemotherapy is one of the standard treatments of lung adenocarcinoma. This study was designed to investigate the efficacy and safety of bevacizumab combined with chemotherapy in symptomatic brain metastases from lung adenocarcinoma that are not suitable for local treatments, and to explore the predictive value of baseline serum vascular endothelial growth factor (VEGF) for the treatment.Methods: We retrospectively reviewed 14 consecutive patients, between Jan 2015 and Jul 2017, with brain metastases from lung adenocarcinoma who received bevacizumab and chemotherapy to determine efficacy and toxicity. Kaplan-Meier method was used to estimate survival curves, and univariate and multivariate analyses were performed by Cox proportional hazard model. The primary endpoints were objective response rate (ORR) and intracranial ORR (iORR). The secondary endpoints were progression-free survival (PFS), intracranial PFS (iPFS), overall survival (OS) and disease control rate (DCR).Results: The efficacy of 12 patient was evaluated. Overall ORR was 25% (3/12) and the iORR of brain lesions was 33.3% (4/12). DCR was 75% (9/12). The median OS was 18.3 months, the median PFS was 6.7 months, and the median iPFS was 12 months. After 2 cycles of bevacizumab, 10 patients showed improved symptoms of central nervous system (CNS), and the symptom control rate was 83.3% (10/12). Head MRI showed that edema in the brain was greatly reduced in 6 patients, resulting in the lessened usage of dexamethasone. iPFS was significantly shorter in high VEGF group (3.6 vs. 8.0 m, P=0.02), and multivariate analysis showed a significant correlation between iPFS and serum baseline VEGF level (P=0.023). The most commonly adverse events of bevacizumab included leukopenia [5 (35.7%)], fatigue [3 (21.4%)], thrombocytopenia [3 (21.4%)], anemia [2 (14.3%)], which were mostly degree I and II.Conclusions: This study showed bevacizumab combined with chemotherapy could effectively control intracranial lesions, relieve symptoms, and improve the quality of life and survival of patients with brain metastases from lung adenocarcinoma. Serum baseline VEGF may be a predictor of efficacy of bevacizumab plus chemotherapy in the treatment of brain metastases from lung adenocarcinoma.