2015-06-02 00:00:00来源：医脉通阅读：20次
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在2015年ASCO年会6月1日下午的肉瘤口头报告专场上，比利时鲁汶大学医院的Patrick Schöffski带来的一项研究表明，艾日布林可延长晚期脂肪细胞肉瘤和平滑肌肉瘤患者的总生存（摘要号LBA10502）。医脉通对此进行了报道。
ASCO专家Gary K.Schwartz对该研究评论说，“对于这种极其难治的疾病，即使是能前进一小步都是值得的。这项研究的结果提醒我们，我们的工作远未完成。必须要权衡艾日布林（eribulin）带来的生存获益与患者承受的毒性负担。”
在该研究团队此前报道过的一项临床2期研究中（Schöffski et al.Lancet Oncol.2011；NCT00413192）中，晚期软组织肉瘤患者有32%为平滑肌肉瘤（LMS），47%为脂肪细胞肉瘤（ADI）。这些患者接受微管动力阻滞剂艾日布林可以在12周的时间终点获得无进展生存（PFS）。在此基础上，这项临床3期试验（NCT01327885）比较了使用艾日布林或达卡巴嗪治疗晚期LMS和ADI患者的总生存。
研究纳入了患有晚期高度/中度LMS或者去分化、粘液型、圆形细胞或多形性ADI并且不可通过手术和/或放射治疗治愈的≥18岁的患者。患者ECOG评分≤2，既往接受≥2种包括蒽环霉素在内的标准系统性治疗药物。把患者按1:1随机分为艾日布林组（在第一天及第八天静注1.4mg/m2)和达卡巴嗪组(在第一天静注850-1200mg/m2)，每21天为一个周期，直到发生疾病进展。
首要终点为总生存（OS）,次要终点为无进展生存期（PFS）、12周PFS率和安全性。
随机分组共有452人，67%为女性（79%＜65岁），艾日布林组有228人、达卡巴嗪组有224人。艾日布林组和达卡巴嗪组中位总生存期分别为13.5和11.5个月（HR=0.768，95% CI 0.618～0.954；P=0.017）。两组的PFS为2.6个月（HR=0.877，95% CI 0.710～1.085；P=0.229）。
艾日布林组和达卡巴嗪组12周PFS率分别为33%和29%。艾日布林组和达卡巴嗪组分别有26%和14%的患者需要减少剂量，有8%和5%的患者由于治疗诱发的不良事件（TEAEs）而中止治疗。与达卡巴嗪组相比，TEAEs更易在发生在艾日布林组，包括嗜中性白血球减少症（44% vs 24%）、发热（28% vs 14%）、外周感觉神经异常（20% vs 4%）和秃头症（35% vs. 3%）；3级（63% vs 53%）、4级（26% vs 20%）和致命性（28% vs 6%）TEAEs发生也如上所示。血小板减少症更易发生于达卡巴嗪组（28% vs 6%）。
这项临床3期艾日布林试验在经治的晚期LMS或ADI患者中达到了OS这一首要目标。艾日布林的毒副反应与之前的研究相一致，没有发现意料外或新的毒性。
会议专题》》》2015年ASCO年会专题报道
摘要原文（摘要号LBA10502）
Background: In a phase II study of pts with advanced soft tissue sarcoma, 32% and 47% of pts with LMS and ADI respectively, treated with the microtubule dynamics inhibitor eribulin achieved progression-free survival (PFS) at the 12 wk timepoint (Schöffski et al. Lancet Oncol. 2011; NCT00413192). Based on these findings, this phase III study (NCT01327885) compared overall survival (OS) in pts with advanced LMS and ADI treated with eribulin or dacarbazine.
Methods: Pts aged ≥ 18 yrs with advanced high/intermediate grade LMS or dedifferentiated, myxoid, round cell or pleomorphic variants of ADI incurable by surgery and/or radiotherapy were enrolled. Pts had ECOG status ≤ 2 and had received ≥ 2 standard systemic treatment regimens including an anthracycline. Pts were randomized 1:1 to eribulin (1.4 mg/m2, IV on D1 and D8) or dacarbazine (850–1200 mg/m2, IV on D1) every 21 days until disease progression. Primary endpoint was OS. Secondary endpoints included PFS, PFS rate at Wk 12 and safety.
Results: Overall, 452 pts (67% female; 79% < 65 yrs) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR = 0.768, 95% CI 0.618–0.954; P= 0.017). PFS was 2.6 months in both arms (HR = 0.877, 95% CI 0.710–1.085;P= 0.229). PFS rate at Wk 12 was 33% and 29% for eribulin and dacarbazine, respectively. In eribulin and dacarbazine arms, respectively, 26% and 14% of pts required dose reductions and 8% and 5% discontinued due to treatment-emergent adverse events (TEAEs). TEAEs were more frequent in eribulin than dacarbazine arm, including neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%) and alopecia (35% vs. 3%); as were TEAEs of grade 3 (63% vs 53%), grade 4 (26% vs 20%), and fatal TEAEs (4% vs 1%). Thrombocytopenia was more frequent in dacarbazine than eribulin arm (28% vs 6%).
Conclusions: This phase III trial of eribulin trial met its primary objective of OS benefit in pretreated pts with advanced LMS or ADI. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. ClinicalTrials.gov identifier: NCT01327885.