St. James's Institute of Oncology, St. James's University Hospital, Leeds, United Kingdom.
N Engl J Med. 2011 Dec 29;365(26):2484-96. doi: 10.1056/NEJMoa1103799.
Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease.
We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.5 mg per kilogram of body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease. Outcome measures included progression-free survival, first analyzed per protocol and then updated, and interim overall survival.
A total of 1528 women from 11 countries were randomly assigned to one of the two treatment regimens. Their median age was 57 years; 90% had epithelial ovarian cancer, 69% had a serous histologic type, 9% had high-risk early-stage disease, 30% were at high risk for progression, and 70% had stage IIIC or IV ovarian cancer. Progression-free survival (restricted mean) at 36 months was 20.3 months with standard therapy, as compared with 21.8 months with standard therapy plus bevacizumab (hazard ratio for progression or death with bevacizumab added, 0.81; 95% confidence interval, 0.70 to 0.94; P=0.004 by the log-rank test). Nonproportional hazards were detected (i.e., the treatment effect was not consistent over time on the hazard function scale) (P<0.001), with a maximum effect at 12 months, coinciding with the end of planned bevacizumab treatment and diminishing by 24 months. Bevacizumab was associated with more toxic effects (most often hypertension of grade 2 or higher) (18%, vs. 2% with chemotherapy alone). In the updated analyses, progression-free survival (restricted mean) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab (P=0.04 by log-rank test); in patients at high risk for progression, the benefit was greater with bevacizumab than without it, with progression-free survival (restricted mean) at 42 months of 14.5 months with standard therapy alone and 18.1 months with bevacizumab added, with respective median overall survival of 28.8 and 36.6 months.
Bevacizumab improved progression-free survival in women with ovarian cancer. The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression. (Funded by Roche and others; ICON7 Controlled-Trials.com number, ISRCTN91273375.).
血管生成在卵巢癌的生物学中起作用。我们研究了血管内皮生长因子抑制剂贝伐单抗对这种疾病患者生存的影响。
我们将患有卵巢癌的女性随机分配到卡铂（曲线下面积为 5 或 6）和紫杉醇（每平方米体表面积 175 毫克）组，每 3 周给药 6 个周期，或给予该方案加贝伐单抗（7.5 毫克/千克体重），每 3 周同时给药 5 或 6 个周期，并继续治疗 12 个额外周期或直至疾病进展。主要终点包括无进展生存期，首先根据方案进行分析，然后进行更新，以及中期总生存期。
来自 11 个国家的 1528 名女性被随机分配到两种治疗方案之一。她们的中位年龄为 57 岁；90%患有上皮性卵巢癌，69%为浆液性组织学类型，9%患有高危早期疾病，30%有进展高风险，70%为 IIIC 期或 IV 期卵巢癌。标准治疗的 36 个月无进展生存期（受限平均）为 20.3 个月，而标准治疗加贝伐单抗为 21.8 个月（贝伐单抗加用的进展或死亡风险比为 0.81；95%置信区间为 0.70 至 0.94；对数秩检验 P=0.04）。检测到非比例风险（即在危险函数尺度上，治疗效果不一致）（P<0.001），最大效应在 12 个月时出现，此时正好是计划的贝伐单抗治疗结束时间，到 24 个月时逐渐减弱。贝伐单抗与更多的毒副作用相关（最常见的是 2 级或更高级别的高血压）（18%，而单独化疗为 2%）。在更新的分析中，无贝伐单抗的 42 个月无进展生存期（受限平均）为 22.4 个月，有贝伐单抗的为 24.1 个月（对数秩检验 P=0.04）；在进展高风险的患者中，贝伐单抗的获益大于无贝伐单抗，单独标准治疗的 42 个月无进展生存期（受限平均）为 14.5 个月，加用贝伐单抗为 18.1 个月，相应的中位总生存期分别为 28.8 个月和 36.6 个月。
贝伐单抗改善了卵巢癌患者的无进展生存期。在疾病进展高风险的患者中，无进展和总生存的获益更大。（由罗氏等资助；ICON7 对照试验。net 注册号，ISRCTN91273375。）
