HER2阳性转移性乳腺癌患者（新）辅助曲妥珠单抗治疗后一线曲妥珠单抗＋紫杉类再治疗的结局：前瞻性多中心研究
曲妥珠单抗是治疗HER2阳性早期乳腺癌和转移性乳腺癌的支柱，但复发患者再治疗的数据有限。
2016年6月7日，美国《肿瘤标靶》杂志在线发表中国医学科学院附属肿瘤医院徐兵河、复旦大学附属肿瘤医院胡夕春、四川大学华西医院郑鸿、浙江省肿瘤医院王晓稼、哈尔滨医科大学附属肿瘤医院张清媛、郑州大学附属河南省肿瘤医院崔树德、中山大学肿瘤防治中心刘冬耕、广东省人民医院廖宁、南方医科大学肿瘤中心罗荣城、北京协和医院孙强、华中科技大学同济医学院附属同济医院于世英的前瞻性非对照多中心研究报告，评估了曲妥珠单抗＋紫杉类对于HER2阳性转移性乳腺癌中国患者原先（新）辅助曲妥珠单抗治疗后复发的疗效和安全性。
该研究将原先（新）辅助曲妥珠单抗治疗≥9周且无复发间期≥6个月的患者予以曲妥珠单抗＋紫杉醇或多西他赛治疗。主要终点为无进展生存，次要终点包括总有效率、临床获益率、有效持续时间、进展时间、总生存率和安全性。
结果32例患者入选，治疗中位持续时间33.5周。中位无进展生存为9.9个月（95%置信区间6.28～13.63个月）。总有效率为81.3%（95%置信区间63.6%～92.8%），临床获益率（完全缓解＋部分缓解＋疾病稳定≥6个月）为81.3%（95%置信区间63.6%～92.8%）。中位有效持续时间为9.8个月（95%置信区间5.82～11.60个月），中位进展时间为9.9个月（95%置信区间6.28～13.63个月）。总生存中位随访时间为20.1个月，25%总生存时间为25.5个月。安全性可接受，常见不良反应包括白细胞减少（59.4%）、中性粒细胞减少（56.3%）、感觉减退（34.4%）和粒细胞减少（31.3%）。
因此，曲妥珠单抗＋紫杉类再治疗作为一线疗法对于HER2阳性转移性乳腺癌（新）辅助曲妥珠单抗治疗后复发的有效方案，安全性良好，不良反应可耐受且可管理。
Oncotarget. 2016 May 27. [Epub ahead of print]
Outcomes of re-treatment with first-line Trastuzumab plus a taxane in HER2 positive metastatic breast cancer patients after (neo)adjuvant Trastuzumab: A prospective multicenter study.
Xu B, Hu X, Zheng H, Wang X, Zhang Q, Cui S, Liu D, Liao N, Luo R, Sun Q, Yu S.
Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.
West China Hospital , Sichuan University, Chengdu, China.
Zhejiang Cancer Hospital, Hangzhou, China.
Harbin Medical University Cancer Hospital, Harbin, China.
Henan Cancer Hospital & Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
Sun Yat-sen University Cancer Center, Guangzhou, China.
Guangdong General Hospital, Guangzhou, China.
Cancer Center, Southern Medical University, Guangzhou, China.
Peking Union Medical College Hospital, Beijing, China.
Tongji Hospital of Tongji Medical College, Hua Zhong University of Science and Technology, Wuhan, China.
Trastuzumab is the backbone of HER2-positive early breast cancer (eBC) and metastatic breast cancer (mBC) treatment, but limited data exist as to re-treatment in relapsed patients. In this prospective, single arm, multicenter trial, we assessed efficacy and safety of trastuzumab and taxane combination in Chinese patients with HER2-positive mBC relapsed after prior (neo)adjuvant trastuzumab. Patients with previous (neo)adjuvant trastuzumab treatment for≥9 weeks and a relapse-free interval ≥6 months were assigned to trastuzumab treatment with paclitaxel or docetaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), time to progression (TTP), overall survival (OS) and safety profile. Thirty-two patients were enrolled and treated for a median duration of 33.5 weeks. The median PFS was 9.9 months (95% CI, 6.28 - 13.63 months). The ORR was 81.3% (95% CI, 63.6% - 92.8%) and CBR (CR+PR+SD≥6months) was 81.3% (95% CI, 63.6% - 92.8%). The median DOR was 9.8 months (95% CI, 5.82 - 11.60 months) and median TTP was 9.9 months (95% CI, 6.28-13.63 months). OS median follow-up time was 20.1 months and 25% OS time was 25.5 months. The safety profile was acceptable with common adverse events including leukopenia (59.4%), neutropenia (56.3%), hypoaesthesia (34.4%) and granulocytopenia (31.3%). In conclusion, re-treatment with trastuzumab plus a taxane as first-line therapy is an effective regimen for patients with HER2-positive mBC relapsed after (neo)adjuvant trastuzumab. The safety profile was good and the adverse reactions were tolerable and manageable.
KEYWORDS: (Neo)adjuvant trastuzumab; human epidermal growth factor receptor 2 (HER2); metastatic breast cancer; re-treatment; relapse; trastuzumab
PMID: 27276706
DOI: 10.18632/oncotarget.9331