George D. Demetri, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Patrick Schöffski, University Hospitals Leuven, Leuven, Belgium; Giovanni Grignani, Fondazione del Piemonte per l'Oncologia Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Italy; Jean-Yves Blay, Université Claude Bernard and Centre Léon Bérard, Lyon, France; Robert G. Maki, Monter Cancer Center, Lake Success; and Cold Spring Harbor Laboratory, New Hyde Park, NY; Brian A. Van Tine, Barnes and Jewish Hospital, Washington University in St. Louis, St. Louis, MO; Thierry Alcindor, McGill University Health Centre, Montreal, Quebec, Canada; Robin L. Jones, The Royal Marsden Hospital, Institute of Cancer Research, London, United Kingdom; David R. D'Adamo and Matthew Guo, Eisai, Woodcliff Lake, NJ; and Sant Chawla, Sarcoma Oncology Center, Santa Monica, CA.
J Clin Oncol. 2017 Oct 20;35(30):3433-3439. doi: 10.1200/JCO.2016.71.6605. Epub 2017 Aug 30.
Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.
一项比较艾瑞布林与达卡巴嗪治疗晚期脂肪肉瘤（LPS）或平滑肌肉瘤患者的 III 期研究显示，艾瑞布林组的总生存期（OS）有显著改善，且毒性可管理。我们现在报告该 III 期试验中 LPS 患者艾瑞布林与达卡巴嗪有效性和安全性的组织学特异性亚组分析，这是该试验的一个独立随机分层亚组。
纳入年龄≥18 岁的晚期或转移性去分化型、黏液样/圆形细胞型或多形性 LPS 患者，这些患者通过手术或放疗无法治愈，ECOG 体能状态评分≤2 分，且接受过两种或更多种系统治疗方案，其中包括一种含蒽环类药物的方案。患者按 1:1 随机分组，接受甲磺酸艾瑞布林（1.4 mg/m 静脉输注，第 1 天和第 8 天）或达卡巴嗪（850、1000 或 1200 mg/m 静脉输注，第 1 天）治疗，每 21 天为一个周期。分析 OS、无进展生存期（PFS）和安全性。
在 LPS 亚组中，与达卡巴嗪相比，艾瑞布林的 OS 显著改善：分别为 15.6 个月和 8.4 个月（风险比，0.51；95%CI，0.35 至 0.75；P<.001）。在所有评估的 LPS 组织学亚型和所有地理区域均观察到艾瑞布林的 OS 延长。与达卡巴嗪相比，艾瑞布林的 PFS 也得到改善（分别为 2.9 个月和 1.7 个月；风险比，0.52；95%CI，0.35 至 0.78；P=0.0015）。两个治疗组的不良反应相似。
在既往治疗的 LPS 患者中，艾瑞布林与达卡巴嗪相比，OS 和 PFS 显著改善。艾瑞布林是一种治疗 LPS（一种有效的系统治疗方法有限的肉瘤亚型）患者的重要治疗选择。进一步的研究有理由探索艾瑞布林在更早期治疗线以及与其他药物联合应用中的作用。
