恩杂鲁胺用于雄激素受体阳性的三阴性乳腺癌临床疗效解析

乳腺癌 anjiaer 85℃ 0评论

  2018年1月26日,美国临床肿瘤学会《临床肿瘤学杂志》在线发表纽约纪念医院斯隆凯特林癌症中心和康奈尔大学威尔医学院、印第安纳大学西蒙癌症中心、田纳西肿瘤专科协作网、孟菲斯西部医院、佛罗里达癌症专家协作网、德克萨斯肿瘤专科协作网、贝勒医学院查尔斯·萨蒙斯癌症中心、西北大学费恩伯格医学院、芝加哥大学、哈佛大学医学院达纳法伯癌症研究所、英国伦敦玛丽王后大学巴茨癌症研究所、爱尔兰肿瘤研究协作组、比利时布鲁塞尔自由大学朱尔·博尔代研究所、西班牙马德里北切雷罗医院克拉拉·坎帕尔综合癌症中心、拉蒙-卡哈尔大学医院、巴塞罗那瓦尔·希伯伦肿瘤研究所与巴塞尔加肿瘤研究所、安斯泰来、麦迪韦逊的II期研究报告,评价了恩杂鲁胺对局部晚期或转移性雄激素受体阳性三阴性乳腺癌患者的抗肿瘤活性和安全性。

 

  该单组非盲II期研究(MDV3100-11)通过对乳腺癌进行优化的免疫组织化学法,从7个国家45个临床研究机构入组雄激素受体阳性(肿瘤细胞核雄激素受体染色>0%)局部晚期或转移性(除了中枢神经系统转移)三阴性乳腺癌患者118例,接受恩杂鲁胺160mg每天一次直至疾病进展。主要终点为16周临床获益率。次要终点包括24周临床获益率、无进展生存和安全性。对所有入组患者(意向治疗人群)进行终点分析,对雄激素受体强阳性(肿瘤细胞核雄激素受体表达≥10%)的78例患者进行亚组评定。

 

  结果,经过中位8.1周(范围:0.9~87)治疗,截至2017年3月15日:

  • 临床获益率

  • 全部:25%(95%置信区间:17%~33%)
  • 亚组:33%(95%置信区间:23%~45%)
  • 中位无进展生存

  • 全部:2.9个月(95%置信区间:1.9~3.7)
  • 亚组:3.3个月(95%置信区间:1.9~4.1)
  • 中位总生存

  • 全部:12.7个月(95%置信区间:8.5~仍在随访)
  • 亚组:17.6个月(95%置信区间:11.6~仍在随访)

 

  发生率>2%的唯一治疗相关≥3级不良事件为疲劳(3.4%)。

 

  因此,对于晚期雄激素受体阳性的三阴乳腺癌患者,恩杂鲁胺表现出临床活性,且耐受性良好,相关不良事件与其已知安全性特征一致,为恩杂鲁胺治疗晚期三阴性乳腺癌的III期研究提供了证据。

 

J Clin Oncol. 2018 Jan 26. [Epub ahead of print]

 

Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer.

 

Traina TA, Miller K, Yardley DA, Eakle J, Schwartzberg LS, O’Shaughnessy J, Gradishar W, Schmid P, Winer E, Kelly C, Nanda R, Gucalp A, Awada A, Garcia-Estevez L, Trudeau ME, Steinberg J, Uppal H, Tudor IC, Peterson A, Cortes J.

 

Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Indiana University Simon Cancer Center, Indianapolis, IN; Tennessee Oncology, Nashville; The West Clinic, Memphis, TN; Florida Cancer Specialists, Fort Myers, FL; Texas Oncology-Baylor Charles A. Sammons Cancer Center, US Oncology, Dallas, TX; Northwestern University Feinberg School of Medicine; University of Chicago, Chicago; Astellas Pharma, Northbrook, IL; Barts Cancer Institute, Queen Mary University London, London, United Kingdom; Dana-Farber Cancer Institute, Boston, MA; All Ireland Collaborative Oncology Research Group, Dublin, Ireland; Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium; Centro Integral Oncologico Clara Campal, Hospital Madrid Norte-Sanchinarro; Ramon y Cajal University Hospital, Madrid; Vall d’Hebron Institute of Oncology and Baselga Oncological Institute, Barcelona, Spain; Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; Medivation, San Francisco, CA.

 

PURPOSE: Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC.

 

PATIENTS AND METHODS: Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed ≥ 10% nuclear AR (the evaluable subgroup).

 

RESULTS: Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of > 2%.

 

CONCLUSION: Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

 

PMID: 29373071

 

DOI: 10.1200/JCO.2016.71.3495

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

 

前列腺癌药物用于雄激素受体阳性的三阴性乳腺癌

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