University Hospital Gasthuisberg, Leuven, Belgium.
J Clin Oncol. 2012 Oct 1;30(28):3499-506. doi: 10.1200/JCO.2012.42.8201. Epub 2012 Sep 4.
Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab.
Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival.
Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti-vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities.
Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.
转移性结直肠癌（mCRC）的治疗通常包括氟嘧啶类化疗方案，如输注氟尿嘧啶、亚叶酸钙和伊立替康（FOLFIRI）或氟尿嘧啶、亚叶酸钙和奥沙利铂，通常联合贝伐珠单抗或表皮生长因子受体单克隆抗体。我们研究了在先前接受过奥沙利铂治疗（包括接受过贝伐珠单抗治疗的患者）的 mCRC 患者中，添加新型抗血管生成药物阿柏西普（在美国也称为泽维阿柏西普）联合 FOLFIRI 对患者的影响。
患者随机分配接受阿柏西普（4 mg/kg 静脉注射；612 例）或安慰剂（614 例），每 2 周联合 FOLFIRI 一次。治疗直至疾病进展或不可接受的毒性。主要终点是总生存期。
与安慰剂联合 FOLFIRI 相比，阿柏西普联合 FOLFIRI 显著改善了总生存期（风险比[HR]，0.817；95.34%CI，0.713 至 0.937；P =.0032），中位总生存期分别为 13.50 个月和 12.06 个月。阿柏西普还显著改善了无进展生存期（PFS；HR，0.758；95%CI，0.661 至 0.869；P <.0001），中位 PFS 时间分别为 6.90 个月和 4.67 个月。总生存和 PFS 的影响在包括贝伐珠单抗预处理患者在内的预先指定的亚组分析中表现出一致的趋势。客观缓解率为 19.8%（95%CI，16.4%至 23.2%），阿柏西普联合 FOLFIRI 治疗组高于安慰剂联合 FOLFIRI 治疗组（11.1%，95%CI，8.5%至 13.8%）（P =.0001）。阿柏西普联合 FOLFIRI 治疗相关的不良反应包括特征性的抗血管内皮生长因子作用，还反映了某些化疗相关毒性的发生率增加。
在先前接受过奥沙利铂治疗的 mCRC 患者中，阿柏西普联合 FOLFIRI 与 FOLFIRI 联合安慰剂相比，在统计学上显著提高了患者的生存获益。
