Safety and Efficacy of Epirubicin, Ifosfamide, and Nivolumab as First-Line Treatment for Patients with Undifferentiated Pleomorphic Sarcoma

PURPOSE: This single-arm, phase Ib trial aimed to evaluate the safety and preliminary efficacy of epirubicin, ifosfamide, and nivolumab as first-line treatment for advanced undifferentiated pleomorphic sarcoma (UPS). PATIENTS AND METHODS: Adult patients with a centrally confirmed diagnosis of advanced UPS were eligible. Patients received epirubicin 60 mg/m2 (days 1-2), ifosfamide 3 g/m2 (days 1-3) every 21 days for up to six cycles, and nivolumab 360 mg flat dose intravenously (day 3/each cycle), followed by maintenance nivolumab for one year. The primary endpoint was the determination of the recommended phase II dose (RP2D). RESULTS: Sixteen patients were enrolled with no dose-limiting toxicities observed; the RP2D was established at full-dose epirubicin, ifosfamide, and nivolumab 360 mg. Grade 3 to 4 treatment-related adverse events included neutropenia (62.5%) and anemia (43.8%). The overall response rate was 68.8%, with 94% of patients experiencing tumor shrinkage. The median progression-free survival was 9.9 months (95% confidence interval, 7-12.7), and the median overall survival was not reached. CONCLUSIONS: The combination of epirubicin, ifosfamide, and nivolumab is a safe, feasible, and highly active treatment for advanced UPS.