Investigative Clinical Oncology (INCO), Candiolo Cancer Institute, FPO-IRCCS, Provincial Road 142, 10060, Candiolo, Torino, Italy.
Guy's Hospital and Sarah Cannon Research Institute, Great Maze Pond, London, SE1 9RT, United Kingdom.
Eur J Cancer. 2019 Mar;109:92-102. doi: 10.1016/j.ejca.2018.12.022. Epub 2019 Jan 29.
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).
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.
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.
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.
许多转移性人表皮生长因子受体 2（HER2）阳性乳腺癌（BC）患者在疾病过程中的某个时间是曲妥珠单抗-美坦新偶联物（T-DM1）治疗的候选者。KAMILLA 评估了先前接受过治疗的 HER2 阳性局部晚期或转移性 BC（晚期 BC）患者接受 T-DM1 的安全性。
KAMILLA（NCT01702571）是一项单臂、开放标签、国际、IIIb 期安全性研究，纳入了先前接受过化疗和 HER2 靶向药物治疗用于转移性 BC（MBC）或在辅助治疗完成后 6 个月内进展的 HER2 阳性晚期 BC 患者。患者接受 T-DM1（3.6mg/kg，每 3 周 1 次）治疗，直至出现不可接受的毒性、停药或疾病进展。
在 2002 例接受治疗的患者中，中位年龄为 55 岁（范围 26-88；373[18.6%]岁≥65 岁），1321 例（66.0%）接受过≥2 线转移性治疗，398 例（19.9%）基线时有中枢神经系统转移。1862 例（93.0%）患者发生了不良事件（AE），427 例（21.3%）患者发生了严重 AE。751 例（37.5%）患者发生了≥3 级 AE；最常见的三种（个体监管医学词典活动术语）是贫血（3.0%）、血小板减少症（2.7%）和疲劳（2.5%）。中位无进展生存期（PFS）为 6.9 个月（95%置信区间[CI]，6.0-7.6）。中位总生存期（OS）为 27.2 个月（95%CI，25.5-28.7）。随着先前先进治疗线数的增加（0-1 线与 4+线），PFS 和 OS 中位数从 8.3 个月分别下降到 5.6 个月，从 31.3 个月分别下降到 22.5 个月。
KAMILLA 是迄今为止 T-DM1 治疗患者中最大的队列研究。结果与先前的随机研究一致，从而支持 T-DM1 作为先前接受过治疗的 HER2 阳性晚期 BC 患者安全、耐受和有效的治疗选择。
