Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial.
Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial.
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DOI：
10.1016/s0140-6736(11)60545-x
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发表时间：
2011-05-28
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影响因子：
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通讯作者：
Hainsworth J
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作者：
Herbst RS;Ansari R;Bustin F;Flynn P;Hart L;Otterson GA;Vlahovic G;Soh CH;O'Connor P;Hainsworth J
贝伐单抗和厄洛替尼针对不同的肿瘤生长途径，其毒性作用特征几乎没有重叠。基于评估厄洛替尼加贝伐单抗治疗复发性或难治性非小细胞肺癌 (NSCLC) 的安全性和活性的 1/2 期试验的有希望的结果，我们旨在在 3 期试验中评估该组合的疗效和安全性。在我们的双盲、安慰剂对照、随机 3 期试验 (BeTa) 中，我们招募了在一线治疗失败后到 12 个国家的 177 个研究中心就诊的复发性或难治性 NSCLC 患者。根据计算机生成的随机序列，使用交互式语音应答系统，将患者以一对一的比例随机分配接受厄洛替尼加贝伐单抗（贝伐单抗组）或厄洛替尼加安慰剂（对照组）。主要终点是所有入组患者的总生存期。患者、研究人员和研究人员对治疗分配情况不知情。我们通过计算不良事件的发生率来评估安全性，并收集组织进行生物标志物分析。该试验已在 ClinicalTrials.gov 注册，编号 NCT00130728。贝伐单抗组 317 名对照者和 319 名患者的总生存率没有差异（风险比 [HR] 0·97，95% CI 0·80–1·18，p=0·7583）。贝伐珠单抗组患者的中位总生存期为 9·3 个月 (IQR 4·1–21·6)，而对照组患者的中位总生存期为 9·2 个月 (3·8–20·2)。贝伐单抗组的无进展生存期（3·4 个月 [1·4–8·4]）似乎比对照组（1·7 个月 [1·3–4·1]；HR 0·62，95% CI 0·52–0·75）更长，客观缓解率表明贝伐单抗和厄洛替尼具有一定的临床活性。然而，这些次要终点差异不能被定义为显着，因为该研究预先规定，在进行次要终点测试之前，主要终点必须是显着的，以控制 I 类错误率。在贝伐珠单抗组中，313 名有安全性数据的患者中有 130 名（42%）发生严重不良事件，而对照组有 114 名（36%）发生严重不良事件。贝伐珠单抗组发生 20 例 (6%) 5 级不良事件，包括 2 例动脉血栓栓塞事件，对照组有 14 例 (4%)。在厄洛替尼中添加贝伐单抗并不能改善复发性或难治性 NSCLC 患者的生存率。基因泰克。
Bevacizumab and erlotinib target different tumour growth pathways with little overlap in their toxic-effect profiles. On the basis of promising results from a phase 1/2 trial assessing safety and activity of erlotinib plus bevacizumab for recurrent or refractory non-small-cell lung cancer (NSCLC), we aimed to assess efficacy and safety of this combination in a phase 3 trial. In our double-blind, placebo-controlled, randomised phase 3 trial (BeTa), we enrolled patients with recurrent or refractory NSCLC who presented to 177 study sites in 12 countries after failure of first-line treatment. Patients were randomly allocated in a one-to-one ratio to receive erlotinib plus bevacizumab (bevacizumab group) or erlotinib plus placebo (control group) according to a computer-generated randomisation sequence by use of an interactive voice response system. The primary endpoint was overall survival in all enrolled patients. Patients, study staff, and investigators were masked to treatment assignment. We assessed safety by calculation of incidence of adverse events and tissue was collected for biomarker analyses. This trial is registered with ClinicalTrials.gov, number NCT00130728. Overall survival did not differ between 317 controls and 319 patients in the bevacizumab group (hazard ratio [HR] 0·97, 95% CI 0·80–1·18, p=0·7583). Median overall survival was 9·3 months (IQR 4·1–21·6) for patients in the bevacizumab group compared with 9·2 months (3·8–20·2) for controls. Progression-free survival seemed to be longer in the bevacizumab group (3·4 months [1·4–8·4]) than in the control group (1·7 months [1·3–4·1]; HR 0·62, 95% CI 0·52–0·75) and objective response rate suggested some clinical activity of bevacizumab and erlotinib. However, these secondary endpoint differences could not be defined as significant because the study prespecified that the primary endpoint had to be significant before testing of secondary endpoints could be done, to control type I error rate. In the bevacizumab group, 130 (42%) of 313 patients with safety data had a serious adverse event, compared with 114 (36%) controls. There were 20 (6%) grade 5 adverse events, including two arterial thromboembolic events, in the bevacizumab group, and 14 (4%) in the control group. Addition of bevacizumab to erlotinib does not improve survival in patients with recurrent or refractory NSCLC. Genentech.