Wu Wei, Deng Heran, Rao Nanyan, You Na, Yang Yaping, Cao Minghui, Liu Jieqiong
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road 107#, Guangzhou, 510120, China.
Department of Statistical Science, School of Mathematics and Southern China Research Center of Statistical Science, Sun Yat-Sen University, Guangzhou, 510275, China.
Trials. 2017 Oct 25;18(1):497. doi: 10.1186/s13063-017-2228-5.
The response to neoadjuvant chemotherapy (NAC) varies by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) statuses, with responses being lower in ER-positive, HER2-negative tumors as compared with ER-negative, HER2-positive or triple-negative tumors. Neoadjuvant endocrine therapy (NET) is an attractive alternative to NAC for ER-positive, HER2-negative cancer. However, a prior trial comparing NET with standard NAC in ER-positive tumor showed that the difference of response was not significant. Studies demonstrated that the mTOR inhibitor everolimus could sensitize breast tumors to endocrine therapy. A pilot open-label, randomized trial has been designed to evaluate the feasibility, efficacy and tolerability of neoadjuvant everolimus plus letrozole versus NAC in treating postmenopausal women with ER-positive, HER2-negative breast cancer.
Forty postmenopausal women with non-metastatic ER-positive, HER2-negative invasive breast cancer with a primary tumor > 2 cm or positive axillary lymph node(s) proved by biopsy will be randomly (1:1) enrolled from Sun Yat-Sen Memorial Hospital to receive neoadjuvant everolimus plus letrozole for 18 weeks or fluorouracil, epirubicin plus cyclophosphamide (FEC) for six cycles before surgery. Primary outcome is the feasibility of the trial. Secondary outcome measures include ultrasound response rate, pathological complete response rate, breast-conserving surgery rate, toxicities, and changes in the percentages of peripheral blood CD4 T cells, CD8 T cells, T helper cells, regulatory T cells, and NK cells.
This is the first study to determine the feasibility, efficacy and tolerability of head-to-head neoadjuvant everolimus plus letrozole versus neoadjuvant FEC in treating postmenopausal women with ER-positive, HER2-negative breast cancer. The trial will provide evidence to assess the feasibility of a future multicenter, randomized controlled trial, and will provide valuable clinical data of the immunoregulatory effect of everolimus in breast cancer.
ClinicalTrials.gov registry, ID: NCT02742051 . Registered on 7 April 2016.
新辅助化疗（NAC）的反应因雌激素受体（ER）和人表皮生长因子受体2（HER2）状态而异，与ER阴性、HER2阳性或三阴性肿瘤相比，ER阳性、HER2阴性肿瘤的反应较低。新辅助内分泌治疗（NET）是ER阳性、HER2阴性癌症NAC的一种有吸引力的替代方案。然而，之前一项在ER阳性肿瘤中比较NET与标准NAC的试验表明，反应差异不显著。研究表明，mTOR抑制剂依维莫司可使乳腺肿瘤对内分泌治疗敏感。一项开放性、随机试验已设计完成，旨在评估新辅助依维莫司联合来曲唑与NAC治疗绝经后ER阳性、HER2阴性乳腺癌女性的可行性、疗效和耐受性。
40例绝经后非转移性ER阳性、HER2阴性浸润性乳腺癌女性，其原发性肿瘤>2 cm或经活检证实腋窝淋巴结阳性，将从中山大学附属孙逸仙纪念医院随机（1:1）入组，接受新辅助依维莫司联合来曲唑治疗18周，或在手术前接受氟尿嘧啶、表柔比星加环磷酰胺（FEC）治疗6个周期。主要结局是试验的可行性。次要结局指标包括超声反应率、病理完全缓解率、保乳手术率、毒性以及外周血CD4 T细胞、CD8 T细胞、辅助性T细胞、调节性T细胞和自然杀伤细胞百分比的变化。
这是第一项确定新辅助依维莫司联合来曲唑与新辅助FEC直接对比治疗绝经后ER阳性、HER2阴性乳腺癌女性的可行性、疗效和耐受性的研究。该试验将为评估未来多中心随机对照试验的可行性提供证据，并将提供依维莫司在乳腺癌中免疫调节作用的有价值临床数据。
ClinicalTrials.gov注册库，ID：NCT02742051。于2016年4月7日注册。
