Eur J Cancer. 2014 Dec;50(18):3077-88. doi: 10.1016/j.ejca.2014.10.008.
The addition of bevacizumab to paclitaxel or capecitabine has demonstrated improved progression-free survival (PFS) and objective response rate (ORR) as compared with chemotherapy alone in patients with HER2-negative locally recurrent or metastatic breast cancer (LR/MBC). We evaluated the efficacy and safety of first-line therapy of paclitaxel and bevacizumab with or without capecitabine in patients with HER2-negative LR/MBC.
In this multicentre, open-label, randomised phase II trial, women with HER2-negative LR/MBC were randomly assigned in a 1:1 ratio to paclitaxel (90 mg/m2 intravenously [IV] on days 1, 8, and 15) and bevacizumab (10 mg/kg IV on days 1 and 15) every 4 weeks for six cycles, followed by bevacizumab (15 mg/kg IV on day 1) every 3 weeks (AT) or to paclitaxel (90 mg/m2 IV on days 1 and 8), bevacizumab (15 mg/kg IV on day 1) and capecitabine (825 mg/m2 orally twice daily on days 1–14) every 3 weeks for eight cycles, followed by bevacizumab and capecitabine at the same doses every 3 weeks (ATX). The primary end-point was investigator-assessed PFS. Secondary end-points included ORR, duration of response, overall survival (OS) and safety. Exploratory analyses were conducted to evaluate the impact of capecitabine on OS and to validate a novel prognostic model. This trial is registered with EudraCT, number 2006-006058-83.
Median PFS was significantly longer in ATX as compared with AT (11.2 months versus 8.4 months; stratified hazard ratio (HR), 0.52; 95% confidence interval (CI), 0.41–0.67; p < 0.0001). The ORR in ATX patients with measurable disease (n = 268) was higher than that in AT (69% versus 51%; p = 0.01). The median duration of response was 6.8 versus 5.4 months for, respectively, ATX and AT (p < 0.0001). Median OS was 24.2 months for ATX and 23.1 months for AT (p = 0.53). The increased rate of grade 3–4 adverse events related to the addition of capecitabine, being hand-foot syndrome (34% versus 0% for AT) and neutropenia (20% versus 12% for AT), generally did not preclude continuation of treatment. Exploratory analyses indicated that (1) patients receiving capecitabine at some line for treatment have significantly improved OS and (2) a prognostic model can classify patients into three risk groups associated with OS.
In patients with HER2-negative LR/MBC, addition of capecitabine to paclitaxel and bevacizumab significantly improved PFS, ORR and response duration. This combination was reasonably well tolerated and may be considered of use as first-line treatment in rapidly progressive disease.
F. Hoffmann-La Roche Ltd, the Netherlands.
与单独化疗相比，曲妥珠单抗联合紫杉醇或卡培他滨治疗 HER2 阴性局部复发性或转移性乳腺癌（LR/MBC）患者，可改善无进展生存期（PFS）和客观缓解率（ORR）。我们评估了曲妥珠单抗联合贝伐珠单抗加或不加卡培他滨作为 HER2 阴性 LR/MBC 患者一线治疗的疗效和安全性。
在这项多中心、开放标签、随机 2 期试验中，HER2 阴性 LR/MBC 患者按 1:1 的比例随机分配，接受紫杉醇（90 mg/m2 静脉输注[IV]，第 1、8 和 15 天）和贝伐珠单抗（10 mg/kg IV，第 1 和 15 天）每 4 周治疗 6 个周期，随后贝伐珠单抗（15 mg/kg IV，第 1 天）每 3 周（AT）或紫杉醇（90 mg/m2 IV，第 1 和 8 天）、贝伐珠单抗（15 mg/kg IV，第 1 天）和卡培他滨（825 mg/m2 口服，每天 2 次，第 1-14 天）每 3 周治疗 8 个周期，随后贝伐珠单抗和卡培他滨以相同剂量每 3 周（ATX）治疗。主要终点是研究者评估的 PFS。次要终点包括 ORR、缓解持续时间、总生存期（OS）和安全性。进行了探索性分析，以评估卡培他滨对 OS 的影响，并验证一种新的预后模型。该试验在 EudraCT 上注册，编号为 2006-006058-83。
与 AT 相比，ATX 的中位 PFS 显著延长（11.2 个月与 8.4 个月；分层危险比（HR），0.52；95%置信区间（CI），0.41-0.67；p<0.0001）。ATX 组中可测量疾病患者的 ORR 高于 AT 组（69%与 51%；p=0.01）。ATX 和 AT 组的中位缓解持续时间分别为 6.8 个月和 5.4 个月（p<0.0001）。ATX 的中位 OS 为 24.2 个月，AT 为 23.1 个月（p=0.53）。添加卡培他滨后，与 AT 相比，与治疗相关的 3-4 级不良事件发生率增加，包括手足综合征（34%与 AT 组的 0%）和中性粒细胞减少症（20%与 AT 组的 12%），但通常不影响治疗的继续。探索性分析表明，（1）接受卡培他滨治疗的患者的 OS 显著改善；（2）一种预后模型可将患者分为与 OS 相关的三个风险组。
在 HER2 阴性 LR/MBC 患者中，卡培他滨联合紫杉醇和贝伐珠单抗可显著改善 PFS、ORR 和缓解持续时间。该联合治疗耐受性良好，可能被认为是快速进展疾病的一线治疗选择。
罗氏研发（瑞士）有限公司，荷兰。
