The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon’s minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33–63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo–endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.
新辅助内分泌治疗联合常规化疗的作用尚不明确，为此我们开展了一项开放标签、单中心、非随机II期临床试验以评估该联合方案的效果。研究纳入既往未经治疗的II期或III期HR阳性、HER2阴性乳腺癌患者，给予来曲唑2.5 mg联合标准新辅助化疗同步治疗。主要终点为手术时的病理完全缓解（pCR）。采用Simon最小最大两阶段设计，第一阶段需达到pCR率>6%方可进入后续阶段。2017年11月至2020年11月期间，共有53名女性患者入组第一阶段试验。患者中位年龄49岁（范围33-63岁），其中60%为绝经前状态。临床分期II期和III期患者分别占66%和34%，93%的患者存在临床淋巴结阳性。经新辅助化疗-内分泌治疗后，2例患者（4%）达到pCR，未满足进入第二阶段的标准。总体缓解率为83%。中位随访53.7个月期间，3年无病生存率和总生存率分别为87%和98%。中性粒细胞减少是最常见的3/4级不良事件（40%），但极少导致发热性中性粒细胞减少症（4%）。肌痛（32%）、恶心（19%）、便秘（17%）、胃灼热（11%）、口腔黏膜炎（9%）和感觉神经病变（9%）较为常见，但均为1级或2级。术前治疗期间未发生死亡事件。在标准新辅助化疗基础上联合来曲唑治疗安全性良好，且在总体缓解率方面具有获益，但未能提高局部晚期HR阳性、HER2阴性乳腺癌的pCR率。针对该亚型乳腺癌的新辅助治疗策略仍需进一步研究优化。
肿瘤(癌症)患者之家