Sarah Cannon Research Institute, Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA,
Breast Cancer Res Treat. 2013 Dec;142(3):655-65. doi: 10.1007/s10549-013-2764-y. Epub 2013 Nov 21.
Docetaxel-containing chemotherapy improves disease-free survival (DFS) and overall survival in patients with early stage breast cancer. Bevacizumab improves response rate and DFS in metastatic breast cancer. However, adding antivascular endothelial growth factor therapy to anthracycline-containing chemotherapy may increase cardiotoxicity. This trial evaluates the feasibility of adding bevacizumab to three standard adjuvant docetaxel regimens with a primary endpoint of grade ≥3 congestive heart failure (CHF). Phase IIb, randomized, non-comparative study of women with previously untreated node-positive or high-risk node-negative breast cancer. Human epidermal growth factor receptor 2 (HER2)-negative patients were randomized to: (arm A) doxorubicin + cyclophosphamide followed by docetaxel or (arm B) docetaxel + doxorubicin + cyclophosphamide. HER2-positive patients (arm C) received docetaxel + carboplatin + trastuzumab for 52 weeks. All patients received bevacizumab beginning on day 1 for 52 weeks. Safety data in 212 women (mean age = 53.1 years) show that 1 patient each in arm A (1.3 %) and arm C (1.7 %), and 3 patients in arm B (4.0 %) experienced clinical CHF grade ≥3. A decreased ejection fraction was observed in 1 patient each in arms A and C, and cardiac disorder was observed in 12.8, 22.7, and 8.5 % in arms A, B, and C, respectively. A grade 3/4 treatment-emergent adverse event was reported in 82.1, 84.0, and 52.5 % of participants in arms A, B, and C, respectively. Kaplan-Meier estimates of DFS show rates at 24 months of 85.5, 90.4, and 90.4 % in arms A, B, and C, respectively. Adding bevacizumab to three standard docetaxel-based chemotherapy regimens as adjuvant treatment in patients with node-positive and high-risk node-negative breast cancer resulted in a low rate of clinical CHF grade ≥3. Maintenance bevacizumab monotherapy did not identify any new safety signals. Breast cancer recurrence/relapse, secondary malignancies, and death were uncommon, although the follow-up time in this study was relatively short.
多西紫杉醇为基础的化疗可改善早期乳腺癌患者的无病生存期（DFS）和总生存期。贝伐单抗可提高转移性乳腺癌的反应率和 DFS。然而，在蒽环类化疗中加入抗血管内皮生长因子治疗可能会增加心脏毒性。该试验评估了在三个标准辅助多西紫杉醇方案中加入贝伐单抗的可行性，主要终点为 3 级以上充血性心力衰竭（CHF）。对未经治疗的淋巴结阳性或高危淋巴结阴性乳腺癌女性进行 IIb 期、随机、非对照研究。人表皮生长因子受体 2（HER2）阴性患者随机分为：（A 臂）阿霉素+环磷酰胺，随后多西紫杉醇或（B 臂）多西紫杉醇+多柔比星+环磷酰胺。HER2 阳性患者（C 臂）接受多西紫杉醇+卡铂+曲妥珠单抗治疗 52 周。所有患者在第 1 天开始接受贝伐单抗治疗，持续 52 周。在 212 名女性（平均年龄=53.1 岁）的安全性数据中，A 臂（1.3%）和 C 臂（1.7%）各有 1 例患者、B 臂（4.0%）有 3 例患者出现 3 级以上临床 CHF。A 臂和 C 臂各有 1 例患者出现射血分数降低，A 臂、B 臂和 C 臂的心脏疾病分别为 12.8%、22.7%和 8.5%。A、B 和 C 臂的治疗中出现 3 级/4 级治疗相关不良事件的患者分别为 82.1%、84.0%和 52.5%。DFS 的 Kaplan-Meier 估计显示，A、B 和 C 臂的 24 个月时的生存率分别为 85.5%、90.4%和 90.4%。在淋巴结阳性和高危淋巴结阴性乳腺癌患者中，将贝伐单抗加入三种标准的多西紫杉醇为基础的化疗方案中作为辅助治疗，导致 3 级以上临床 CHF 的发生率较低。维持贝伐单抗单药治疗未发现任何新的安全信号。乳腺癌复发/转移、继发性恶性肿瘤和死亡并不常见，尽管该研究的随访时间相对较短。
