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曲妥珠单抗＋恩特星（T-DM1）是抗HER2单克隆抗体类蛋白质与微管蛋白抑制剂类化疗药的缀合物，可以实现精准靶向化疗，适用于抗HER2和化疗失败的HER2阳性乳腺癌转移患者。 2019年1月29日，欧洲癌症治疗研究组织、欧洲癌症组织、欧洲乳腺癌专科医师学会《欧洲癌症杂志》在线发表意大利坎迪奥洛癌症研究所、英国伦敦大学国王学院盖伊医院和莎拉坎农研究所、西班牙米格尔塞维特大学医院、德国慕尼黑大学医院、法国古斯塔夫鲁西研究所、法国北部里尔大学、波尔多癌症治疗中心、荷兰癌症研究所、瑞士罗氏、巴西圣卢卡斯医院的KAMILLA研究报告，评估了T-DM1治疗HER2阳性局部晚期或转移性乳腺癌既往治疗失败患者的的安全性、有效性、耐受性。 该国际多中心单组双队列（全部患者队列、亚洲患者队列）非盲IIIb期研究KAMILLA（NCT01702571）于2012年11月12日～2014年9月29日从40个国家地区入组HER2阳性晚期乳腺癌化疗＋HER2靶向药物转移治疗后或辅助治疗完成后6个月内疾病进展的患者，接受T-DM1（每3周3.6mg/kg）直至出现无法耐受的毒性反应、退出研究或疾病进展。 结果，入组患者共计2002例，中位年龄55岁（范围26～88岁；年龄≥65岁373例，占18.6%），其中1321例（66.0%）接受过至少二线治疗、398例（19.9%）入组时中枢神经系统转移。 不良事件和严重不良事件分别发生于1862例（93.0%）和427例（21.3%）患者。≥3级不良事件发生于751例（37.5%）患者，最常见的三种分别为贫血、血小板减少、疲劳（3.0%、2.7%、2.5%）。 中位无进展生存、中位总生存分别为6.9个月、27.2个月（95%置信区间：6.0～7.6、25.5～28.7）。接受过至多一线治疗与至少四线治疗的患者相比，中位无进展生存、中位总生存分别由8.3个月、31.3个月，减少至5.6个月、22.5个月。 因此，KAMILLA是目前样本量最大的T-DM1治疗患者队列研究，代表了更广泛的人群，结果与既往随机对照研究一致，从而证实了T-DM1对于HER2阳性晚期乳腺癌既往治疗失败患者的安全性、耐受性和有效性。 相关阅读 Eur J Cancer. 2019 Jan 29;109:92-102. Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: Primary results from the KAMILLA study cohort 1. Filippo Montemurro, Paul Ellis, Antonio Anton, Rachel Wuerstlein, Suzette Delaloge, Jacques Bonneterre, Nathalie Quenel-Tueux, Sabine C. Linn, Candiolo Cancer Institute, Candiolo, Torino, Italy; Guy's Hospital and Sarah Cannon Research Institute, London, United Kingdom; University Hospital Miguel Servet, Zaragoza, Spain; University Hospital Munich, Ludwig Maximilian University, Munich, Germany; Institut Gustave Roussy, Villejuif, France; Université Lille Nord de France, Lille, France; Institut Bergonié Comprehensive Cancer Center, Bordeaux, France; The Netherlands Cancer Institute, Amsterdam, the Netherlands; F. Hoffmann-La Roche Ltd., Basel, Switzerland; Hospital Sao Lucas, Porto Alegre, Brazil. HIGHLIGHTS
BACKGROUND: Many patients with metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) are candidates for trastuzumab emtansine (T-DM1) treatment sometime in their disease history. KAMILLA evaluated safety of T-DM1 in patients with previously treated HER2-positive locally advanced or metastatic BC (advanced BC). METHODS: KAMILLA (NCT01702571) is a single-arm, open-label, international, phase IIIb safety study of patients with HER2-positive advanced BC with progression after prior treatment with chemotherapy and a HER2-directed agent for MBC or within 6 months of completing adjuvant therapy. Patients received T-DM1 (3.6 mg/kg every 3 weeks) until unacceptable toxicity, withdrawal or disease progression. RESULTS: Among 2002 treated patients, median age was 55 years (range, 26-88; 373 [18.6%] aged ≥65 years), 1321 (66.0%) received ≥2 prior metastatic treatment lines and 398 (19.9%) had baseline central nervous system metastases. Adverse events (AEs) and serious AEs occurred in 1862 (93.0%) and 427 (21.3%) patients, respectively. Grade ≥3 AEs occurred in 751 (37.5%) patients; the three most common (individual Medical Dictionary for Regulatory Activity terms) were anaemia (3.0%), thrombocytopaenia (2.7%) and fatigue (2.5%). Median progression-free survival (PFS) was 6.9 months (95% confidence interval [CI], 6.0-7.6). Median overall survival (OS) was 27.2 months (95% CI, 25.5-28.7). With increasing lines of prior advanced therapy (0-1 versus 4+), median PFS and OS decreased numerically from 8.3 to 5.6 months and from 31.3 to 22.5 months, respectively. CONCLUSIONS: KAMILLA is the largest cohort of T-DM1-treated patients studied to date. Results are consistent with prior randomised studies, thereby supporting T-DM1 as safe, tolerable and efficacious treatment for patients with previously treated HER2-positive advanced BC. KEYWORDS: Ado-trastuzumab emtansine, Receptor, ErbB-2, Receptor, epidermal growth factor, Drug-related side effects and adverse reactions, Malignant neoplasm of breast, Clinical trial, Phase III DOI: 10.1016/j.ejca.2018.12.022
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