A randomized phase 2 study of temozolomide and bevacizumab or nab-paclitaxel, carboplatin, and bevacizumab in patients with unresectable stage IV melanoma: A North Central Cancer Treatment Group study, N0775

Background: Increasing evidence shows chemotherapy in combination with vascular endothelial growth factor (VEGF) inhibition is a clinically active therapy for patients with metastatic melanoma (MM). Methods: A phase 2 trial was conducted in chemotherapy-naive patients with unresectable stage IV MM who were randomized to temozolomide (200 mg/m² on days 1 through 5) and bevacizumab (10 mg/kg intravenously on days 1 and 15) every 28 days (Regimen TB) or nab-paclitaxel (100 mg/m², or 80 mg/m² post-addendum 5 secondary to toxicity, on days 1, 8, and 15), bevacizumab (10 mg/kg on days 1 and 15), and carboplatin (area under the curve [AUC] 6 on day 1, or AUC 5 post-addendum 5) every 28 days (Regimen ABC). Accrual goal was 41 patients per regimen. The primary aim of this study was to estimate progression-free survival rate at 6 months (PFS6) in each regimen. A regimen would be considered promising if its PFS6 rate was > 60%. Results: Ninety-three eligible patients (42 TB and 51 ABC) were enrolled. The majority of patients had M1c disease (20 TB and 26 ABC). The median PFS and overall survival times with ABC were 6.7 months and 13.9 months, respectively. Median PFS time and median overall survival with TB were 3.8 months and 12.3 months, respectively. The most common severe toxicities (≥ grade 3) in both regimens were cytopenias, fatigue, and thrombosis. Among the first 41 patients enrolled onto each regimen, PFS6 rate was 32.8% (95% confidence interval: 21.1%-51.2%) for TB and 56.1% (90% confidence interval: 44.7%-70.4%) for ABC. Conclusions: The addition of bevacizumab to nab-paclitaxel and carboplatin shows promising activity despite tolerability issues. Cancer 2013.