A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naive patients with metastatic melanoma
A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naive patients with metastatic melanoma
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DOI：
10.1093/annonc/mdv324
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发表时间：
2015-11-01
影响因子：
50.5
通讯作者：
Hauschild, A.
中科院分区：
文献类型：
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作者：
Hersh, E. M.;Del Vecchio, M.;Hauschild, A.
背景资料：在一项III期随机对照试验中评价了白蛋白结合型紫杉醇与达卡巴嗪在转移性黑色素瘤患者中的疗效和安全性。患者和方法：未经化疗的IV期黑素瘤患者每4周在第1、8和15天接受nab-紫杉醇150 mg/m2或每3周接受达卡巴嗪1000 mg/m2.主要终点是独立影像学检查的无进展生存期（PFS）;次要终点是总生存期（OS）。结果：共有529例患者被随机分配至紫杉醇组（n = 264）或达卡巴嗪组（n = 265）.基线特征平衡良好。大多数患者为男性（66%），东部肿瘤协作组状态为0（71%），M1 c期疾病（65%）。nabpaclitaxel组的中位PFS（主要终点）为4.8个月，达卡巴嗪组为2.5个月[风险比（HR），0.792; 95.1%置信区间（CI）0.631- 0.992; P = 0.044]。紫杉醇组的中位OS为12.6个月，达卡巴嗪组为10.5个月（HR，0.897; 95.1% CI 0.738- 1.089; P = 0.271）。nab-紫杉醇与达卡巴嗪独立评估的总体缓解率分别为15%与11%（P = 0.239），疾病控制率（DCR）分别为39%与27%（P = 0.004）。最常见的3级治疗相关不良事件是神经病变（nab-紫杉醇，25%对达卡巴嗪，0%; P < 0.001）和中性粒细胞减少症（nab-紫杉醇，20%对达卡巴嗪，10%; P = 0.004）.在任一治疗组中，分泌的酸性和富含半胱氨酸的蛋白质（NAB）状态与PFS之间没有相关性。结论：与达卡巴嗪相比，nab-Paclitazine显著改善了PFS和DCR，具有可管理的安全性。
Background: The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial. Patients and methods: Chemotherapy- naive patients with stage IV melanoma received nab- paclitaxel 150 mg/m2 on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m2 every 3 weeks. The primary end point was progression-free survival ( PFS) by independent radiologic review; the secondary end point was overall survival ( OS). Results: A total of 529 patients were randomized to nab- paclitaxel ( n = 264) or dacarbazine ( n = 265). Baseline characteristics were well balanced. The majority of patients were men ( 66%), had an Eastern Cooperative Oncology Group status of 0 ( 71%), and had M1c stage disease ( 65%). The median PFS ( primary end point) was 4.8 months with nabpaclitaxel and 2.5 months with dacarbazine [ hazard ratio ( HR), 0.792; 95.1% confidence interval ( CI) 0.631- 0.992; P = 0.044]. The median OS was 12.6 months with nab- paclitaxel and 10.5 months with dacarbazine ( HR, 0.897; 95.1% CI 0.738- 1.089; P = 0.271). Independently assessed overall response rate was 15% versus 11% ( P = 0.239), and disease control rate ( DCR) was 39% versus 27% ( P = 0.004) for nab- paclitaxel versus dacarbazine, respectively. The most common grade = 3 treatment- related adverse events were neuropathy ( nab- paclitaxel, 25% versus dacarbazine, 0%; P < 0.001), and neutropenia ( nab- paclitaxel, 20% versus dacarbazine, 10%; P = 0.004). There was no correlation between secreted protein acidic and rich in cysteine ( SPARC) status and PFS in either treatment arm. Conclusions: nab- Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.