Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
Department of Surgery, Leiden University Medical Center, Leiden, Netherlands; Department of Medical Oncology, Leiden University Medical Center, Leiden, Netherlands.
Lancet Oncol. 2017 Sep;18(9):1211-1220. doi: 10.1016/S1470-2045(17)30419-9. Epub 2017 Jul 18.
After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial.
The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5-3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001.
6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0-10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65-69) for the exemestane group and 67% (65-69) for the sequential group (hazard ratio 0·96, 0·88-1·05; p=0·39).
The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible.
Pfizer, Dutch Cancer Foundation.
在中位随访 5 年后，他莫昔芬依西美坦辅助多国试验（TEAM）报告称，在接受早期激素受体阳性乳腺癌治疗的绝经后患者中，依西美坦单药治疗与他莫昔芬序贯治疗后再用依西美坦的无病生存期无差异。由于激素受体阳性乳腺癌的复发风险在诊断后 5 年以上仍呈线性，因此我们分析了该试验的长期随访结果。
TEAM 试验是一项多中心、开放性、随机、对照、III 期试验，纳入了来自 9 个国家的绝经后早期激素受体阳性乳腺癌患者。患者通过计算机生成的随机区组方法（区组大小为 4-8）按 1:1 随机分配至 5 年口服依西美坦单药治疗（25mg，每天一次）或他莫昔芬序贯治疗（20mg，每天一次）后再用依西美坦治疗 5 年的方案。在 IES 试验公布后，方案进行了修订（2004 年 12 月 13 日）。接受他莫昔芬治疗的患者在 2.5-3.0 年后转换为依西美坦治疗，总共治疗 5.0 年。在每个国家中心进行随机分组。在 6 个参与国家收集疾病复发和生存的长期随访数据，并进行意向治疗分析。主要终点为 10 年随访时的无病生存期。该试验在 ClinicalTrials.gov 注册，编号为 NCT00279448 和 NCT00032136；在荷兰试验注册处，编号为 NTR 267；以及伦理委员会试验，编号为 27/2001。
在 TEAM 试验的 9776 例原始患者中，有 6120 例患者纳入了当前的意向治疗分析。中位随访时间为 9.8 年（IQR 8.0-10.3）。随访期间，依西美坦组 3075 例患者中有 921 例（30%）和序贯组 3045 例患者中有 929 例（31%）发生了无病生存事件。依西美坦组和序贯组的 10 年无病生存率分别为 67%（95%CI 65-69）和 67%（65-69）（风险比 0.96，0.88-1.05；p=0.39）。
TEAM 试验的长期研究结果证实，依西美坦单药治疗和他莫昔芬序贯治疗后再用依西美坦作为绝经后激素受体阳性早期乳腺癌的辅助内分泌治疗都是合理的选择。这些结果表明，根据患者的偏好、合并症和耐受性，个体化辅助内分泌治疗策略的机会是可能的。
辉瑞公司、荷兰癌症基金会。
