Frampton James E, Keating Gillian M
Wolters Kluwer Health | Adis, Auckland, New Zealand.
BioDrugs. 2008;22(2):113-20. doi: 10.2165/00063030-200822020-00004.
Bevacizumab, an anti-vascular endothelial growth factor recombinant humanized monoclonal antibody, directly inhibits tumor angiogenesis and hence tumor growth. First-line therapy with intravenous bevacizumab 10 mg/kg every 2 weeks plus subcutaneous interferon-alpha-2a 9 million international units three times weekly has been evaluated in two randomized, double-blind or open-label, multicenter phase III trials (AVOREN [n = 649] and CALGB 90206 [n = 732]). Bevacizumab combination therapy resulted in a median progression-free survival that was significantly (p < or = 0.0001) longer than that seen with placebo plus interferon-[alpha]-2a in AVOREN (10.2 vs 5.4 months) [hazard ratio (HR) 0.63 (95% CI 0.52, 0.75)] and that seen with interferon-alpha-2a alone in CALGB 90206 (8.5 vs 5.2 months). Overall survival data in AVOREN and CALGB 90206 are not yet mature. In the interim overall survival analysis in AVOREN, median overall survival was 19.8 months with placebo plus interferon-alpha-2a, but had not yet been reached with bevacizumab plus interferon-alpha-2a (HR 0.79 [95% CI 0.62, 1.02; p = 0.0670]). The overall tumor response rate with bevacizumab plus interferon-alpha-2a was significantly (p < or = 0.0001) higher than with placebo plus interferon-alpha-2a in AVOREN (31% vs 13%) and that with interferon-alpha-2a alone in CALGB 90206 (25.5% vs 13.1%). Subgroup analyses in AVOREN suggested that interferon-alpha-2a dose reductions (to manage grade > or =3 adverse events attributable to the drug) did not compromise the efficacy of combination treatment with bevacizumab plus interferon-alpha-2a. The addition of bevacizumab to interferon-alpha-2a in AVOREN was generally well tolerated. No unexpected/new adverse events were observed; bevacizumab-associated toxicities were generally of mild intensity.
贝伐单抗是一种抗血管内皮生长因子的重组人源化单克隆抗体，可直接抑制肿瘤血管生成，从而抑制肿瘤生长。两项随机、双盲或开放标签的多中心III期试验（AVOREN [n = 649]和CALGB 90206 [n = 732]）对每2周静脉注射10 mg/kg贝伐单抗加皮下注射α-2a干扰素900万国际单位，每周3次的一线治疗方案进行了评估。在AVOREN试验中，贝伐单抗联合治疗组的无进展生存期（PFS）中位数显著长于安慰剂加α-2a干扰素组（10.2个月对5.4个月）[风险比（HR）0.63（95%CI 0.52, 0.75）]，P <或= 0.0001；在CALGB 90206试验中，贝伐单抗联合治疗组的PFS中位数也显著长于单用α-2a干扰素组（8.5个月对5.2个月）。AVOREN和CALGB 90206试验的总生存期（OS）数据尚未成熟。在AVOREN试验的中期OS分析中，安慰剂加α-2a干扰素组的OS中位数为19.8个月，而贝伐单抗加α-2a干扰素组尚未达到（HR 0.79 [95%CI 0.62, 1.02；P = 0.0670]）。在AVOREN试验中，贝伐单抗加α-2a干扰素组的总体肿瘤缓解率显著高于安慰剂加α-2a干扰素组（31%对13%），P <或= 0.0001；在CALGB 90206试验中，贝伐单抗加α-2a干扰素组的总体肿瘤缓解率也显著高于单用α-2a干扰素组（25.5%对13.1%）。AVOREN试验的亚组分析表明，减少α-2a干扰素剂量（以处理≥3级药物相关不良事件）不会影响贝伐单抗加α-2a干扰素联合治疗的疗效。在AVOREN试验中，在α-2a干扰素基础上加用贝伐单抗一般耐受性良好。未观察到意外/新的不良事件；与贝伐单抗相关的毒性一般为轻度。
