Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial
Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial
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DOI：
10.1016/s1470-2045(17)30419-9
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发表时间：
2017-09-01
期刊：
影响因子：
51.1
通讯作者：
van de Velde, Cornelis J. H.
中科院分区：
文献类型：
--
作者：
Derks, Marloes G. M.;Blok, Erik J.;van de Velde, Cornelis J. H.
经过5年的中位随访，他莫昔芬依西美坦辅助治疗多国（TEAM）试验报告，在绝经后早期激素受体阳性乳腺癌患者中，依西美坦单药治疗与他莫昔芬序贯方案治疗无病生存率无差异。由于激素受体阳性乳腺癌的复发风险在诊断后5年内仍然是线性的，我们分析了这项试验的长期随访结果。TEAM试验是一项多中心、开放标签、随机、对照的3期试验，包括来自9个国家的绝经后早期激素受体阳性乳腺癌患者。通过计算机生成的随机排列区组方法（区组大小4-8）将患者随机分配（1：1）至5年口服阿司美坦单药治疗（25 mg，每日一次）或口服他莫昔芬（20 mg，每日一次），随后接受阿司美坦治疗，总持续时间为5年。IES试验发表后，对方案进行了修订（2004年12月13日）。分配到他莫昔芬组的患者在2.5-3.0年后转换为阿司美坦治疗，总治疗时间为5.0年。在每个国家集中进行随机化。在六个参与国家收集了疾病复发和生存的长期随访数据，并通过意向治疗进行分析。主要终点是随访10年时的无病生存率。该试验注册于ClinicalTrials.gov，注册号为NCT 00279448和NCT 00032136;注册于荷兰试验注册处，注册号为NTR 267;注册于伦理委员会试验，注册号为27/2001。中位随访时间为9.8年（IQR 8.0-10.3）。在随访期间，阿司美坦组3075例患者中有921例（30%）和序贯组3045例患者中有929例（31%）发生无病生存事件。10年无病生存率为67%（95% CI 65-69），序贯治疗组为67%（65-69）（危害比0.96，0.88-1.05; p=0.39）。TEAM试验的长期结果证实，单用阿司美坦和序贯他莫昔芬后阿司美坦治疗作为辅助治疗都是合理的选择绝经后激素受体阳性早期乳腺癌患者的内分泌治疗。这些结果表明，根据患者的偏好、合并症和耐受性，可能有机会相应地个性化辅助内分泌策略。
Background 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.Methods 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.Findings 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. Diseasefree 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).Interpretation 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.