Department of Breast Oncology, Niigata Cancer Center Hospital, Niigata, Japan.
Department of Surgery, Breast Oncology, National Hospital Organization Osaka National Hospital, Osaka, Japan.
Cancer Med. 2019 Sep;8(12):5468-5481. doi: 10.1002/cam4.2423. Epub 2019 Jul 30.
Our aim was to investigate the efficacy and safety of initial neoadjuvant endocrine therapy with exemestane alone followed by tailored treatment, either continued exemestane monotherapy or exemestane plus docetaxel-cyclophosphamide (TC) combination therapy, in postmenopausal patients with primary invasive estrogen receptor-positive, human epidermal growth factor receptor 2-negative, stage I-IIIA breast cancer and Ki67 labeling index ≤30%. In this open-label phase II study, patients initially received exemestane 25 mg/d for 12 weeks. Responders were defined as patients who achieved complete response (CR), partial response (PR) with Ki67 labeling index ≤5% after treatment, or stable disease with Ki67 labeling index ≤5% both before and after treatment. For the subsequent 12 weeks, exemestane monotherapy was continued for responders (group A), whereas nonresponders received exemestane plus four cycles of TC (docetaxel 75 mg/m and cyclophosphamide 600 mg/m every 3 weeks) (group B). Clinical response rate (ie the proportion of patients with CR or PR) at 24 weeks was the primary endpoint. Of 64 patients provisionally enrolled between December 2010 and May 2016, 58 (median age 60 years) started the study treatment. Five patients discontinued treatment in the initial exemestane monotherapy period, and 39 completed the study treatment. Clinical response rates at 8-12 and 24 weeks were 71% (10/14, 95% confidence interval [CI] 41.9%-91.6%) and 57% (8/14, 95% CI 28.9%-82.3%), respectively, in group A, and 16% (4/25, 95% CI 4.5%-36.1%) and 56% (14/25, 95% CI 34.9%-75.6%), respectively, in group B. Grade ≥3 adverse events were reported in 8% (1/15) and 53% (20/38) in group A and group B, respectively. The tailored treatment maintained the favorable clinical response to exemestane alone in responders and improved clinical response in nonresponders. TRIAL NUMBER: UMIN000004752 (UMIN Clinical Trials Registry).
我们的目的是研究在绝经后原发性浸润性雌激素受体阳性、人表皮生长因子受体 2 阴性、ⅠB 期至ⅢA 期、Ki67 标记指数≤30%的乳腺癌患者中，单独使用依西美坦进行初始新辅助内分泌治疗，然后根据治疗反应，分别继续使用依西美坦单药治疗或依西美坦联合多西他赛-环磷酰胺（TC）联合治疗的疗效和安全性。在这项开放标签的Ⅱ期研究中，患者最初接受依西美坦 25mg/d，治疗 12 周。缓解定义为治疗后完全缓解（CR）或部分缓解（PR），且 Ki67 标记指数≤5%，或治疗前后 Ki67 标记指数均≤5%，且疾病稳定。对于后续的 12 周，对缓解的患者继续依西美坦单药治疗（A 组），而未缓解的患者则接受依西美坦联合 4 个周期的 TC（多西他赛 75mg/m2 和环磷酰胺 600mg/m2，每 3 周 1 次）（B 组）。24 周时的临床缓解率（即 CR 或 PR 患者的比例）为主要终点。2010 年 12 月至 2016 年 5 月期间，64 例患者被暂定入组，其中 58 例（中位年龄 60 岁）开始研究治疗。5 例患者在初始依西美坦单药治疗期间停止治疗，39 例完成了研究治疗。A 组 8-12 周和 24 周的临床缓解率分别为 71%（10/14，95%置信区间 [CI] 41.9%-91.6%）和 57%（8/14，95% CI 28.9%-82.3%），B 组分别为 16%（4/25，95% CI 4.5%-36.1%）和 56%（14/25，95% CI 34.9%-75.6%）。A 组和 B 组分别有 8%（1/15）和 53%（20/38）的患者发生≥3 级不良事件。个体化治疗在缓解者中维持了单独使用依西美坦的良好临床缓解效果，并提高了不缓解者的临床缓解效果。试验编号：UMIN000004752（UMIN 临床试验注册）。
