Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103)
Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103)
复制标题
DOI：
10.1200/jco.2018.79.2028
复制
发表时间：
2018-09-01
影响因子：
45.3
通讯作者：
Sledge, George W., Jr.
中科院分区：
文献类型：
--
作者：
Miller, Kathy D.;O'Neill, Anne;Sledge, George W., Jr.
目的贝伐单抗可改善转移性乳腺癌患者的无进展生存期，但不能改善总生存期。 E5103 测试了贝伐珠单抗在人类表皮生长因子受体 2 阴性疾病患者辅助治疗中的效果。患者和方法患者按照 1:2:2 的比例分配接受安慰剂联合多柔比星和环磷酰胺 (AC)，然后每周接受紫杉醇治疗（A 组），仅在 AC 和紫杉醇期间接受贝伐单抗治疗（B 组），或者在 AC 和紫杉醇期间接受贝伐单抗治疗，然后接受每周一次紫杉醇治疗。贝伐珠单抗单药治疗 10 个周期（C 组）。对随机分配进行分层，并根据 AC 计划的选择调整贝伐珠单抗剂量。 C 组中，放射治疗和激素治疗与贝伐珠单抗同时进行。主要终点是侵袭性无病生存期 (IDFS)。 结果 纳入了 4994 名患者。中位年龄为 52 岁； 64% 的患者雌激素受体阳性，27% 淋巴结阴性，78% 接受剂量密集 AC。所有组中与化疗相关的不良事件（包括骨髓抑制和神经病变）相似。 3 级高血压在贝伐珠单抗治疗的患者中更为常见，但血栓形成、蛋白尿和出血则不然。 A、B 和 C 组 15 个月时临床充血性心力衰竭的累积发生率分别为 1.0%、1.9% 和 3.0%。贝伐珠单抗暴露量低于预期，B 组中约 24% 的患者和 C 组中约 55% 的患者在完成计划治疗之前停用贝伐珠单抗。 A 组的五年 IDFS 为 77%（95% CI，71% 至 81%），B 组为 76%（95% CI，72% 至 80%），C 组为 80%（95% CI，77% 至 83%）。患有人类表皮生长因子受体2阴性乳腺癌的高危人群。鉴于早期停药率较高，较长时间的贝伐单抗治疗不太可能可行。
PurposeBevacizumab improves progression-free survival but not overall survival in patients with metastatic breast cancer. E5103 tested the effect of bevacizumab in the adjuvant setting in patients with human epidermal growth factor receptor 2-negative disease.Patients and MethodsPatients were assigned 1:2:2 to receive placebo with doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (arm A), bevacizumab only during AC and paclitaxel (arm B), or bevacizumab during AC and paclitaxel followed by bevacizumab monotherapy for 10 cycles (arm C). Random assignment was stratified and bevacizumab dose adjusted for choice of AC schedule. Radiation and hormonal therapy were administered concurrently with bevacizumab in arm C. The primary end point was invasive disease-free survival (IDFS).ResultsFour thousand nine hundred ninety-four patients were enrolled. Median age was 52 years; 64% of patients were estrogen receptor positive, 27% were lymph node negative, and 78% received dose-dense AC. Chemotherapy-associated adverse events including myelosuppression and neuropathy were similar across all arms. Grade 3 hypertension was more common in bevacizumab-treated patients, but thrombosis, proteinuria, and hemorrhage were not. The cumulative incidence of clinical congestive heart failure at 15 months was 1.0%, 1.9%, and 3.0% in arms A, B, and C, respectively. Bevacizumab exposure was less than anticipated, with approximately 24% of patients in arm B and approximately 55% of patients in arm C discontinuing bevacizumab before completing planned therapy. Five-year IDFS was 77% (95% CI, 71% to 81%) in arm A, 76% (95% CI, 72% to 80%) in arm B, and 80% (95% CI, 77% to 83%) in arm C.ConclusionIncorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer. Longer duration bevacizumab therapy is unlikely to be feasible given the high rate of early discontinuation.