FDA drug approval summary:: Bevacizumab (Avastin®) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer
FDA drug approval summary:: Bevacizumab (Avastin®) plus carboplatin and paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer
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DOI：
10.1634/theoncologist.12-6-713
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发表时间：
2007-01-01
期刊：
影响因子：
5.8
通讯作者：
Pazdur, Richard
中科院分区：
文献类型：
--
作者：
Cohen, Martin H.;Gootenberg, Joe;Pazdur, Richard
2006年10月11日，美国驻S.食品和药物管理局批准贝伐单抗（Avastin（R）; Genentech，Inc.，South San弗朗西斯科，CA），与卡铂和紫杉醇联合给药，用于不可切除、局部晚期、复发或转移性、非鳞状、非小细胞肺癌（NSCLC）患者的初始治疗。批准是基于总生存期（OS）的显著改善。由东部肿瘤协作组（ECOG）在IIIB/IV期非鳞状NSCLC的化疗初治患者中进行的随机、开放标签、多中心临床试验评估了贝伐单抗加卡铂和紫杉醇（BV/CP，n = 434）与单独的卡铂和紫杉醇（CP，n = 444）。根据II期研究中接受BV/CP方案的13例鳞状组织学患者中的4例发生危及生命或致死性咯血，排除鳞状组织学或主要鳞状组织学患者。在878例随机化患者中，中位年龄为63岁，46%为女性，76%为IV期疾病，12%为IIIB期疾病伴恶性胸腔积液，11%的患者疾病复发，40%的患者ECOG体能状态评分为0。接受BV/CP的患者的OS明显长于单独接受CP的患者（中位OS，12.3个月vs 10.3个月;风险比[HR]，0.80; p = 0.013，分层对数秩检验）。虽然在大多数亚组中观察到一致的效果，但在探索性分析中，在女性中未观察到生存益处的证据（HR，0.99; 95%置信区间，0.79 - 1.25）。在接受BV/CP的患者中更常见的严重和危及生命的不良事件是中性粒细胞减少症（27%对17%），疲劳（16%对13%），高血压（8% vs 0.7%），感染，无中性粒细胞减少（7% vs 3%），血栓形成/栓塞（5% vs 3%），肺炎或肺浸润（5% vs 3%），感染伴3级或4级中性粒细胞减少（5%对2%）、发热性中性粒细胞减少（5%对2%）、低钠血症（4%对1%）、蛋白尿（3%对0）和头痛（3%对0.5%）。在接受贝伐单抗治疗的患者中，致死性治疗相关不良事件为肺出血最严重的，有时是致命的，贝伐单抗毒性是胃肠道穿孔，伤口愈合并发症，出血，动脉血栓栓塞事件，高血压危象，肾病综合征、充血性心力衰竭和血小板减少性脓毒症。接受贝伐珠单抗治疗的患者最常见的不良事件是虚弱、疼痛、腹痛、头痛、高血压、腹泻、恶心、呕吐、厌食、口腔炎、便秘、上呼吸道感染、鼻衄、呼吸困难、剥脱性皮炎和蛋白尿。
On October 11, 2006, the U. S. Food and Drug Administration granted approval for bevacizumab (Avastin(R); Genentech, Inc., South San Francisco, CA), administered in combination with carboplatin and paclitaxel, for the initial treatment of patients with unresectable, locally advanced, recurrent, or metastatic, nonsquamous, non-small cell lung cancer (NSCLC). Approval is based on a significant improvement in overall survival (OS).A randomized, open label, multicenter clinical trial, conducted by the Eastern Cooperative Oncology Group (ECOG), in chemotherapy- naive patients with stage IIIB/IV nonsquamous NSCLC, evaluated bevacizumab plus carboplatin and paclitaxel (BV/CP, n = 434) versus carboplatin and paclitaxel alone (CP, n = 444). Exclusion of patients with squamous or predominantly squamous histology was based on life-threatening or fatal hemoptysis occurring in 4 of 13 patients with squamous histology who received a BV/CP regimen in a phase II study.Among the 878 randomized patients, the median age was 63, 46% were female, 76% had stage IV disease, 12% had stage IIIB disease with malignant pleural effusion, 11% had recurrent disease, and 40% had an ECOG performance status score of 0. OS was significantly longer in patients receiving BV/CP than in those receiving CP alone (median OS, 12.3 versus 10.3 months; hazard ratio [HR], 0.80; p = .013, stratified log rank test). Although a consistent effect was observed across most subgroups, in an exploratory analysis, evidence of a survival benefit was not observed in women (HR, 0.99; 95% confidence interval, 0.79-1.25).Severe and life-threatening adverse events occurring more frequently in patients receiving BV/CP were neutropenia (27% versus 17%), fatigue (16% versus 13%), hypertension (8% versus 0.7%), infection without neutropenia (7% versus 3%), thrombosis/embolism (5% versus 3%), pneumonitis or pulmonary infiltrate (5% versus 3%), infection with grade 3 or 4 neutropenia (5% versus 2%), febrile neutropenia (5% versus 2%), hyponatremia (4% versus 1%), proteinuria (3% versus 0), and headache (3% versus 0.5%). Fatal, treatment-related adverse events in patients receiving bevacizumab were pulmonary hemorrhage (2.3% versus 0.5%), gastrointestinal hemorrhage, central nervous system infarction, gastrointestinal perforation, myocardial infarction, and neutropenic sepsis.The most serious, and sometimes fatal, bevacizumab toxicities are gastrointestinal perforation, wound healing complications, hemorrhage, arterial thromboembolic events, hypertensive crisis, nephrotic syndrome, congestive heart failure, and neutropenic sepsis. The most common adverse events in patients receiving bevacizumab are asthenia, pain, abdominal pain, headache, hypertension, diarrhea, nausea, vomiting, anorexia, stomatitis, constipation, upper respiratory infection, epistaxis, dyspnea, exfoliative dermatitis, and proteinuria.