Department of Medical Oncology, San Raffaele Institute, Milan, Italy.
Lancet Oncol. 2011 Mar;12(3):236-44. doi: 10.1016/S1470-2045(11)70033-X. Epub 2011 Feb 25.
Treatment with adjuvant trastuzumab for 1 year improves disease-free survival and overall survival in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess disease-free survival and overall survival after a median follow-up of 4 years for patients enrolled on the Herceptin Adjuvant (HERA) trial.
The HERA trial is an international, multicentre, randomised, open-label, phase 3 trial comparing treatment with trastuzumab for 1 and 2 years with observation after standard neoadjuvant, adjuvant chemotherapy, or both in patients with HER2-positive early breast cancer. The primary endpoint was disease-free survival. After a positive first interim analysis at a median follow-up of 1 year for the comparison of treatment with trastuzumab for 1 year with observation, event-free patients in the observation group were allowed to cross over to receive trastuzumab. We report trial outcomes for the 1-year trastuzumab and observation groups at a median follow-up of 48·4 months (IQR 42·0-56·5) and assess the effect of the extensive crossover to trastuzumab. Our analysis was by intention-to-treat. The HERA trial is registered with the European Clinical Trials Database, number 2005-002385-11.
The HERA trial population comprised 1698 patients randomly assigned to the observation group and 1703 to the 1-year trastuzumab group. Intention-to-treat analysis of disease-free survival showed a significant benefit in favour of patients in the 1-year trastuzumab group (4-year disease-free survival 78·6%) compared with the observation group (4-year disease-free survival 72·2%; hazard ratio [HR] 0·76; 95% CI 0·66-0·87; p<0·0001). Intention-to-treat analysis of overall survival showed no significant difference in the risk of death (4-year overall survival 89·3%vs 87·7%, respectively; HR 0·85; 95% CI 0·70-1·04; p=0·11). Overall, 885 patients (52%) of the 1698 patients in the observation group crossed over to receive trastuzumab, and began treatment at median 22·8 months (range 4·5-52·7) from randomisation. In a non-randomised comparison, patients in the selective-crossover cohort had fewer disease-free survival events than patients remaining in the observation group (adjusted HR 0·68; 95% CI 0·51-0·90; p=0·0077). Higher incidences of grade 3-4 and fatal adverse events were noted on 1-year trastuzumab than in the observation group. The most common grade 3 or 4 adverse events, each in less than 1% of patients, were congestive cardiac failure, hypertension, arthralgia, back pain, central-line infection, hot flush, headache, and diarrhoea.
Treatment with adjuvant trastuzumab for 1 year after chemotherapy is associated with significant clinical benefit at 4-year median follow-up. The substantial selective crossover of patients in the observation group to trastuzumab was associated with improved outcomes for this cohort.
F Hoffmann-La Roche, Michelangelo Foundation.
曲妥珠单抗辅助治疗 1 年可改善人表皮生长因子受体 2（HER2）阳性早期乳腺癌患者的无病生存和总生存。我们旨在评估 HER2 阳性早期乳腺癌患者在中位随访 4 年后的无病生存和总生存情况，这些患者参与了曲妥珠单抗辅助治疗（HERA）试验。
HERA 试验是一项国际性、多中心、随机、开放性、III 期临床试验，比较了曲妥珠单抗治疗 1 年与 2 年与标准新辅助、辅助化疗或两者联合治疗后观察的患者的疗效。主要终点是无病生存。在中位随访 1 年的首次阳性中期分析后，与观察相比，曲妥珠单抗治疗 1 年的无病患者允许交叉接受曲妥珠单抗治疗。我们报告了中位随访 48.4 个月（IQR 42.0-56.5）时 1 年曲妥珠单抗和观察组的试验结果，并评估了广泛交叉至曲妥珠单抗的效果。我们的分析是基于意向治疗。HERA 试验在欧洲临床试验数据库中注册，编号为 2005-002385-11。
HERA 试验人群包括 1698 例随机分配至观察组和 1703 例随机分配至 1 年曲妥珠单抗组的患者。无病生存的意向治疗分析显示，1 年曲妥珠单抗组患者（4 年无病生存率为 78.6%）明显优于观察组患者（4 年无病生存率为 72.2%；风险比[HR]为 0.76；95%CI 为 0.66-0.87；p<0.0001）。总生存的意向治疗分析显示，两组患者的死亡风险无显著差异（4 年总生存率分别为 89.3%和 87.7%；HR 为 0.85；95%CI 为 0.70-1.04；p=0.11）。总体而言，观察组 1698 例患者中有 885 例（52%）交叉接受曲妥珠单抗治疗，自随机分组后中位时间 22.8 个月（范围为 4.5-52.7）开始治疗。在非随机比较中，选择性交叉队列的患者无病生存事件少于观察组仍在观察组的患者（调整 HR 为 0.68；95%CI 为 0.51-0.90；p=0.0077）。1 年曲妥珠单抗组的 3-4 级和致命不良事件发生率高于观察组。最常见的 3 级或 4 级不良事件，每种不良事件均不到 1%的患者，为充血性心力衰竭、高血压、关节痛、背痛、中心静脉置管感染、热潮红、头痛和腹泻。
化疗后曲妥珠单抗辅助治疗 1 年与中位随访 4 年的显著临床获益相关。观察组患者大量选择性交叉至曲妥珠单抗治疗与该队列的改善结局相关。
罗氏公司，米开朗基罗基金会。
