A randomized, controlled phase III trial of nab-Paclitaxel versus dacarbazine in chemotherapy-naïve patients with metastatic melanoma

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.