Hersh E M, Del Vecchio M, Brown M P, Kefford R, Loquai C, Testori A, Bhatia S, Gutzmer R, Conry R, Haydon A, Robert C, Ernst S, Homsi J, Grob J J, Kendra K, Agarwala S S, Li M, Clawson A, Brachmann C, Karnoub M, Elias I, Renschler M F, Hauschild A
Department of Medicine, Arizona Cancer Center, Tucson, USA
Department of Medical Oncology, Fondazione IRCCS National Tumor Institute, Milan, Italy.
Ann Oncol. 2015 Nov;26(11):2267-74. doi: 10.1093/annonc/mdv324. Epub 2015 Sep 26.
The efficacy and safety of nab-paclitaxel versus dacarbazine in patients with metastatic melanoma was evaluated in a phase III randomized, controlled trial.
Chemotherapy-naïve patients with stage IV melanoma received nab-paclitaxel 150 mg/m(2) on days 1, 8, and 15 every 4 weeks or dacarbazine 1000 mg/m(2) every 3 weeks. The primary end point was progression-free survival (PFS) by independent radiologic review; the secondary end point was overall survival (OS).
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 nab-paclitaxel 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.
nab-Paclitaxel significantly improved PFS and DCR compared with dacarbazine, with a manageable safety profile.
在一项III期随机对照试验中评估了纳米白蛋白结合型紫杉醇与达卡巴嗪治疗转移性黑色素瘤患者的疗效和安全性。
初治的IV期黑色素瘤患者每4周在第1、8和15天接受纳米白蛋白结合型紫杉醇150mg/m²，或每3周接受达卡巴嗪1000mg/m²。主要终点是通过独立影像学评估的无进展生存期（PFS）；次要终点是总生存期（OS）。
共有529例患者被随机分配至纳米白蛋白结合型紫杉醇组（n = 264）或达卡巴嗪组（n = 265）。基线特征均衡良好。大多数患者为男性（66%），东部肿瘤协作组状态为0（71%），且为M1c期疾病（65%）。纳米白蛋白结合型紫杉醇组的中位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]。纳米白蛋白结合型紫杉醇组的中位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）。独立评估的总缓解率分别为15%和11%（P = 0.239），纳米白蛋白结合型紫杉醇组和达卡巴嗪组的疾病控制率（DCR）分别为39%和27%（P = 0.004）。最常见的≥3级治疗相关不良事件是神经病变（纳米白蛋白结合型紫杉醇组为25%，达卡巴嗪组为0%；P < 0.001）和中性粒细胞减少（纳米白蛋白结合型紫杉醇组为20%，达卡巴嗪组为10%；P = 0.004）。在任何一个治疗组中，富含半胱氨酸的酸性分泌蛋白（SPARC）状态与PFS均无相关性。
与达卡巴嗪相比，纳米白蛋白结合型紫杉醇显著改善了PFS和DCR，且安全性可控。
