Wielkopolskie Centrum Pulmonologii i Torakochirurgii, Poznań University of Medical Sciences, Augustyna Szamarzewskiego 62, 61-001 Poznań, Poland.
J Clin Oncol. 2012 Oct 10;30(29):3640-7. doi: 10.1200/JCO.2012.42.6932. Epub 2012 Sep 10.
PURPOSE: To compare the efficacy of aflibercept (ziv-aflibercept), a recombinant human fusion protein targeting the vascular endothelial growth factor (VEGF) pathway, with or without docetaxel in platinum-pretreated patients with advanced or metastatic nonsquamous non-small-cell lung cancer. PATIENTS AND METHODS: In this international, double-blind, placebo-controlled phase III trial, 913 patients were randomly assigned to (ziv-)aflibercept 6 mg/kg intravenous (IV; n = 456) or IV placebo (n = 457), both administered every 3 weeks and in combination with docetaxel 75 mg/m(2). The primary end point was overall survival (OS). Other efficacy outcomes, safety, and immunogenicity were also assessed. RESULTS: Patient characteristics were balanced between arms; 12.3% of patients had received prior bevacizumab. (Ziv-)Aflibercept did not improve OS (hazard ratio [HR], 1.01; 95% CI, 0.87 to 1.17; stratified log-rank P = .90). The median OS was 10.1 months (95% CI, 9.2 to 11.6 months) for (ziv-)aflibercept and 10.4 months (95% CI, 9.2 to 11.9 months) for placebo. In exploratory analyses, median progression-free survival was 5.2 months (95% CI, 4.4 to 5.6 months) for (ziv-)aflibercept versus 4.1 months (95% CI, 3.5 to 4.3 months) for placebo (HR, 0.82; 95% CI, 0.72 to 0.94; P = .0035); overall response rate was 23.3% of evaluable patients (95% CI, 19.1% to 27.4%) in the (ziv-)aflibercept arm versus 8.9% (95% CI, 6.1% to 11.6%; P < .001) in the placebo arm. Grade ≥ 3 adverse events occurring more frequently in the (ziv-)aflibercept arm versus the placebo arm were neutropenia (28.0% v 21.1%, respectively), fatigue (11.1% v 4.2%, respectively), stomatitis (8.8% v 0.7%, respectively), and hypertension (7.3% v 0.9%, respectively). CONCLUSION: The addition of (ziv-)aflibercept to standard docetaxel therapy did not improve OS. In exploratory analyses, secondary efficacy end points did seem to be improved in the (ziv-)aflibercept arm. The study regimen was associated with increased toxicities, consistent with known anti-VEGF and chemotherapy-induced events.
目的：比较阿柏西普（泽维-阿柏西普）与多西他赛联合或不联合多西他赛在铂类预处理的晚期或转移性非鳞状非小细胞肺癌患者中的疗效，阿柏西普是一种针对血管内皮生长因子（VEGF）途径的重组人融合蛋白。
患者和方法：在这项国际、双盲、安慰剂对照的 III 期试验中，913 名患者被随机分配至（泽维-）阿柏西普 6 mg/kg 静脉（IV；n = 456）或 IV 安慰剂（n = 457）组，每 3 周给药一次，与多西他赛 75 mg/m²联合用药。主要终点为总生存期（OS）。还评估了其他疗效结局、安全性和免疫原性。
结果：患者特征在两组之间平衡；12.3%的患者曾接受贝伐珠单抗治疗。（泽维-）阿柏西普并未改善 OS（风险比[HR]，1.01；95%CI，0.87 至 1.17；分层对数秩 P =.90）。（泽维-）阿柏西普组的中位 OS 为 10.1 个月（95%CI，9.2 至 11.6 个月），安慰剂组为 10.4 个月（95%CI，9.2 至 11.9 个月）。在探索性分析中，（泽维-）阿柏西普组的中位无进展生存期为 5.2 个月（95%CI，4.4 至 5.6 个月），安慰剂组为 4.1 个月（95%CI，3.5 至 4.3 个月）（HR，0.82；95%CI，0.72 至 0.94；P =.0035）；可评估患者的总缓解率为 23.3%（95%CI，19.1%至 27.4%），安慰剂组为 8.9%（95%CI，6.1%至 11.6%；P <.001）。（泽维-）阿柏西普组比安慰剂组更常发生≥3 级不良事件为中性粒细胞减少症（分别为 28.0%和 21.1%）、疲劳（分别为 11.1%和 4.2%）、口腔炎（分别为 8.8%和 0.7%）和高血压（分别为 7.3%和 0.9%）。
结论：（泽维-）阿柏西普联合标准多西他赛治疗并未改善 OS。在探索性分析中，（泽维-）阿柏西普组的次要疗效终点似乎有所改善。研究方案与增加的毒性有关，与已知的抗 VEGF 和化疗诱导的事件一致。
Zotero 插件