Buonadonna Angela, Benson Charlotte, Casanova Jose, Kasper Bernd, López Pousa Antonio, Mazzeo Filomena, Brodowicz Thomas, Penel Nicolas
aDepartment of Oncology, Medical Oncology, CRO, National Cancer Institute (IRCCS), Aviano (PN), Italy bSarcoma Unit, Medical Oncology, Royal Marsden Hospital, London, UK cLocomotive Apparatus Tumor Unit, Orthopedic Service, Coimbra University Medical Center, Coimbra, Portugal dSarcoma Unit, Interdisciplinary Tumor Center, Mannheim University Medical Center, University of Heidelberg, Germany eMedical Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain fMedical Oncology, L'Institut Roi Albert II, Bruxelles, Belgium gClinical Division of Oncology, Medical University Vienna - General Hospital, Austria hCentre Oscar Lambret, General Oncology, Lille, France.
Anticancer Drugs. 2017 Nov;28(10):1157-1165. doi: 10.1097/CAD.0000000000000560.
This prospective, noninterventional study is the first phase IV trial designed to evaluate trabectedin in patients with advanced soft tissue sarcoma in real-life clinical practice across Europe. To be included in the study, patients must have received more than or equal to one cycle of trabectedin and be currently on treatment. The primary endpoint was progression-free survival as defined by investigators. The secondary endpoints included objective response rate, disease control rate, time to progression and the growth modulation index (GMI), overall survival, and an assessment of the cancer-related symptoms and safety. A total of 218 patients from 41 European centers were evaluated. Patients received a median of six cycles per patient, mostly on an outpatient basis (n=132; 60.6%). The median progression-free survival was 5.9 months, with 70 and 49% of patients free from progression at 3 and 6 months after treatment, respectively. Three (1.4%) patients achieved a complete response and 55 (25.2%) patients achieved a partial response for an objective response rate of 26.6%. A total of 85 (39.0%) patients had disease stabilization for a disease control rate of 65.6%. The median GMI was 0.8, with 5.1 and 38.8% of patients with a GMI of greater than 1.1 to less than 1.33 and greater than or equal to 1.33, respectively. The median overall survival was 21.3 months. Febrile neutropenia (2.3% of patients), neutropenia, nausea, and pneumonia (1.4% each) were the most common trabectedin-related grade 3/4 serious adverse drug reactions. Trabectedin confers clinically meaningful long-term benefits to patients with multiple soft tissue sarcoma histotypes, being either comparable or better than those observed previously in clinical trials, and with a manageable safety profile.
这项前瞻性、非干预性研究是第一项IV期试验，旨在评估曲贝替定在欧洲现实临床实践中治疗晚期软组织肉瘤患者的效果。要纳入该研究，患者必须已接受过至少一个周期的曲贝替定治疗且目前正在接受治疗。主要终点是研究者定义的无进展生存期。次要终点包括客观缓解率、疾病控制率、进展时间和生长调节指数（GMI）、总生存期，以及对癌症相关症状和安全性的评估。对来自欧洲41个中心的218例患者进行了评估。患者每人接受的中位周期数为6个周期，大多为门诊治疗（n = 132；60.6%）。中位无进展生存期为5.9个月，分别有70%和49%的患者在治疗后3个月和6个月时无疾病进展。3例（1.4%）患者达到完全缓解，55例（25.2%）患者达到部分缓解，客观缓解率为26.6%。共有85例（39.0%）患者疾病稳定，疾病控制率为65.6%。中位GMI为0.8，分别有5.1%和38.8%的患者GMI大于1.1至小于1.33以及大于或等于1.33。中位总生存期为21.3个月。发热性中性粒细胞减少（占患者的2.3%）、中性粒细胞减少、恶心和肺炎（各占1.4%）是最常见的与曲贝替定相关的3/4级严重药物不良反应。曲贝替定可为多种软组织肉瘤组织学类型的患者带来具有临床意义的长期益处，与之前在临床试验中观察到的效果相当或更好，且安全性可控。
