Departments of Surgery, Medical Oncology, and Medical Statistics, Leiden University Medical Center, Leiden, Netherlands; Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, the Netherlands; Department of Internal Medicine, Reinier de Graaff Hospital, Delft, the Netherlands; Dutch Breast Cancer Research Group, Amsterdam, the Netherlands; Department of Surgery, Netherlands Cancer Institute, Amsterdam, the Netherlands.
J Natl Cancer Inst. 2018 Jan 1;110(1). doi: 10.1093/jnci/djx134.
The optimal duration of extended endocrine therapy beyond five years after initial aromatase inhibitor-based adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer is still unknown. Therefore, we conducted a clinical trial to compare two different extended endocrine therapy durations.
In the randomized phase III IDEAL trial, postmenopausal patients with hormone receptor-positive breast cancer were randomly allocated to either 2.5 or five years of letrozole after the initial five years of any endocrine therapy. The primary end point was disease free survival (DFS), and secondary end points were overall survival (OS), distant metastasis-free interval (DMFi), new primary breast cancer, and safety. Hazard ratios (HRs) were determined using Cox regression analysis. All analyses were by intention-to-treat principle.
A total of 1824 patients were assigned to either 2.5 years (n = 909) or five years (n = 915) of letrozole, with a median follow-up of 6.6 years. A DFS event occurred in 152 patients in the five-year group, compared with 163 patients in the 2.5-year group (HR = 0.92, 95% confidence interval [CI] = 0.74 to 1.16). OS (HR = 1.04, 95% CI = 0.78 to 1.38) and DMFi (HR = 1.06, 95% CI = 0.78 to 1.45) were not different between both groups. A reduction in occurrence of second primary breast cancer was observed with five years of treatment (HR = 0.39, 95% CI = 0.19 to 0.81). Subgroup analysis did not identify patients who benefit from five-year extended therapy.
This study showed no superiority of five years over 2.5 years of extended adjuvant letrozole after an initial five years of adjuvant endocrine therapy.
初始芳香化酶抑制剂辅助治疗绝经后激素受体阳性乳腺癌五年后，延长内分泌治疗的最佳持续时间仍不清楚。因此，我们进行了一项临床试验，比较两种不同的延长内分泌治疗持续时间。
在随机 III 期 IDEAL 试验中，绝经后激素受体阳性乳腺癌患者随机分配接受初始内分泌治疗 5 年后，分别接受 2.5 年或 5 年的来曲唑治疗。主要终点是无病生存期（DFS），次要终点是总生存期（OS）、远处无转移间隔（DMFi）、新发原发性乳腺癌和安全性。使用 Cox 回归分析确定风险比（HR）。所有分析均采用意向治疗原则。
共 1824 例患者被分配至 2.5 年（n=909）或 5 年（n=915）来曲唑组，中位随访时间为 6.6 年。5 年组中 152 例患者发生 DFS 事件，2.5 年组中 163 例患者发生 DFS 事件（HR=0.92，95%CI=0.74 至 1.16）。OS（HR=1.04，95%CI=0.78 至 1.38）和 DMFi（HR=1.06，95%CI=0.78 至 1.45）在两组之间无差异。5 年治疗组新发原发性乳腺癌发生率降低（HR=0.39，95%CI=0.19 至 0.81）。亚组分析未发现有患者从 5 年延长治疗中获益。
本研究表明，初始辅助内分泌治疗 5 年后，5 年延长辅助来曲唑治疗并不优于 2.5 年。
