Pegase 03: A prospective randomized phase III trial of FEC with or without high-dose thiotepa, cyclophosphamide and autologous stem cell transplantation in first-line treatment of metastatic breast cancer

Pegase 03 is a multicenter prospective randomized phase III trial evaluating the impact of first-line high-dose chemotherapy (HDC) with stem cell support on overall survival (OS), disease-free survival (DFS) and response rate in 308 patients with histologically proven metastatic breast cancer responding to induction therapy. Eligible patients received four induction cycles with FEC 100 (5-fluorouracil 500 mg/m², epirubicin 100 mg/m², cyclophosphamide 500 mg/m²). Patients with objective response (N = 179) were randomized to one cycle of HDC (cyclophosphamide 6000 mg/m² and thiotepa 800 mg/m² (CHUT)) and stem cell support (N = 88), or no further treatment (N = 91). All patients were observed until disease progression or death. One toxic death occurred after CHUT. Other toxicities were manageable. The response rate at 3 months was higher in the intensification arm: 82.7% (25.3% complete response (CR)) versus 59.2% (14.1% CR) (P = 0.0002). Median follow-up was 48 months. Median DFS was 11 and 6.6 months in the intensification and the observation arms, respectively (P = 0.0001). There was no survival difference: 33.6 versus 27.3% OS at 3 years (P = 0.8) and 22.9 versus 22.3 months median time to relapse in the intensification and observation arms, respectively. In this randomized trial, HDC with CHUT improved DFS but not OS, corroborating findings from earlier trials.