医脉通编译整理，转载请务必注明出处。
2015年ASCO年会将于5月29日--6月2日在美国芝加哥召开。6月1日上午的乳腺癌口头报告专场，将公布3期临床研究CALGB 40503的结果，该研究评估了贝伐单抗加入一线来曲唑内分泌治疗用于激素受体阳性晚期乳腺癌的疗效（摘要号501）。医脉通对此进行了报道。
临床前研究数据表明,雌二醇可调节生理和病理条件下的血管生成。乳腺肿瘤内高水平血管内皮生长因子（VEGF）与对内分泌治疗（ET）的应答下降相关。研究人员进行的一项多中心、开放标签的III 期试验，将贝伐单抗(B)加到一线内分泌治疗药物来曲唑(L)中，治疗激素受体(HR)阳性患者的晚期乳腺癌患者。研究旨在验证抗VEGF治疗是否会延缓在内分泌治疗中的疾病进展。
入组患者以1:1的比例随机分为来曲唑组（每天口服2.5 毫克）或来曲唑+贝伐单抗组（每3周静脉注射贝伐单抗15mg/kg）。患者按是否有可测量病灶（是/否）及无病间期（≤或>24个月）进行亚组分层分析。患者经医师筛选后接受他莫昔芬治疗，入组一项平行的、 随机的二期临床试验。研究的主要终点是无进展生存（PFS），定义为从入组到疾病进展 (RECIST v 1.0) 或各种原因死亡的时间。次要终点是缓解率、临床受益率、总生存期（OS）和不良事件 (CTCAE v3.0）。以90%的效能达到风险比为0.67，需要252例患者及274个PFS事件（对应中位PFS从6个月增长到9个月）。
从2008年5月至2011年11月，350例患者被随机分组纳入该III期临床试验。343例患者接受治疗，并进行相应的疗效分析。患者的中位年龄为58（25-87）。在36个月的随访后、 观察到258例患者的PFS 。来曲唑+贝伐单抗组的中位数PFS是20个月，而来曲唑组为16 个月（HR=0.74，95%CI：0.58-0.95； p=0.016）。两组OS没有显著性差异(来曲唑+贝伐单抗组为47个月，曲唑组为41个月；HR=0.84；95%CI，0.61-1.15；p=0.27）。来曲唑+贝伐单抗组和来曲唑组最常见的3/4级毒性，分别是高血压（23 vs 2%）和蛋白尿（11 vs 0%）。
将贝伐单抗加入一线来曲唑治疗HR+晚期乳腺癌，可改善 PFS，但增加贝伐单抗相关的毒性。可识别治疗是否有效及耐药的潜在生物标志物正在研究中。临床试验信息： NCT00601900
会议专题》》》2015年ASCO年会专题报道
摘要原文（摘要号501）
Background: Preclinical data suggest estradiol modulates angiogenesis under both physiologic and pathologic conditions. High vascular endothelial growth factor (VEGF) levels in breast tumors have been associated with decreased response to endocrine therapy (ET). We performed a multicenter, open label phase III trial of the addition of bevacizumab (B) to first-line letrozole (L) in patients (pts) with hormone-receptor positive (HR+) advanced breast cancer to test the hypothesis that anti-VEGF therapy may delay progression on ET.
Methods: Pts were randomized 1:1 to L (2.5 mg orally daily) or L+B (15 mg/kg intravenously every 3 weeks) within strata defined by measurable disease (Yes/No) and disease-free interval (≤ / > 24 months (mo)). Pts electing to receive tamoxifen by physician choice were enrolled in a parallel, randomized phase II trial. The primary endpoint was progression-free survival (PFS), defined as time from randomization to progression (RECIST v1.0) or all-cause death. Secondary endpoints were response rate, clinical benefit rate, overall survival (OS) and adverse events (CTCAE v3.0). Three hundred and fifty-two pts and 274 events were needed for 90% power to detect a hazard ratio (HR) of 0.67 (corresponding to an increase in median PFS from 6 to 9 mo).
Results: From May 2008 to November 2011, 350 pts were randomized to the phase III trial. 343 pts received treatment and are included in the efficacy analysis. Median age was 58 (25-87). After 36 mo of additional follow-up, 258 PFS events were observed. Median PFS for L+B was 20 mo vs. 16 mo for L (HR = 0.74, 95% CI: 0.58 - 0.95; p = 0.016). There was no significant difference in OS (L+B, 47 mo vs. L, 41 mo; HR = 0.84; 95% CI, 0.61 - 1.15; p = 0.27). The most frequently reported grade 3/4 toxicities on L+B and L, respectively, were hypertension (23 vs 2%) and proteinuria (11 vs 0%).
Conclusions: Adding B to first-line L improves PFS in HR+ advanced breast cancer with increased B-related toxicity. Updated data will be presented. Correlative studies are underway to identify potential biomarkers of response or resistance to therapy. Supported by U10CA180821, U10CA180882, CA31946, CA180888, CA180858, CA180820, CA180785. Clinical trial information: NCT00601900
