Clinical Trial Unit, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione G. Pascale, Napoli, Italy.
Medical Oncology 2, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padova, Italy.
J Thorac Oncol. 2022 Sep;17(9):1086-1097. doi: 10.1016/j.jtho.2022.05.008. Epub 2022 Jun 1.
Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.
Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.
From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.
The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.
在日本的 JO25567 试验中，贝伐珠单抗联合厄洛替尼延长了 EGFR 突变的晚期 NSCLC 患者的无进展生存期（PFS），但在非亚洲患者中可用的数据有限。BEVERLY 是一项意大利的多中心、随机、III 期研究，旨在评估贝伐珠单抗联合厄洛替尼作为晚期 EGFR 突变的 NSCLC 一线治疗的疗效。
符合条件的患者按 1:1 随机分配至厄洛替尼加贝伐珠单抗或厄洛替尼单药治疗。研究者评估的 PFS 和盲法独立中心审查的 PFS 是共同的主要终点。在检测 0.60 的风险比和双侧 α 错误为 0.05 时，需要 160 例患者中的 126 例事件。该试验在 NCT02633189 和 EudraCT 2015-002235-17 中注册。
从 2016 年 4 月 11 日至 2019 年 2 月 27 日，共 160 例患者随机分为厄洛替尼加贝伐珠单抗组（80 例）和厄洛替尼单药组（80 例）。中位随访 36.3 个月时，研究者评估的中位 PFS 分别为厄洛替尼加贝伐珠单抗组 15.4 个月（95%置信区间[CI]：12.2-18.6）和厄洛替尼单药组 9.6 个月（95%CI：8.2-10.6）（风险比为 0.66，95%CI：0.47-0.92）。盲法独立中心审查的 PFS 分析证实了这一结果。治疗效果存在统计学显著的交互作用与吸烟习惯（p=0.0323），仅在当前或既往吸烟者中观察到 PFS 延长具有临床意义。高血压（≥3 级：24%比 5%）、皮疹（≥3 级：31%比 14%）、血栓栓塞事件（任何级别：11%比 4%）和蛋白尿（任何级别：23%比 6%）在联合治疗中更为常见。
贝伐珠单抗联合厄洛替尼一线治疗可延长意大利 EGFR 突变 NSCLC 患者的 PFS；联合治疗毒性增加，但无意外安全性问题。
