Safety and Efficacy of Epirubicin, Ifosfamide, and Nivolumab as First-line treatment for patients with Undifferentiated Pleomorphic Sarcoma.

Abstract

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 UPS. Adult patients with a centrally confirmed diagnosis of advanced undifferentiated pleomorphic sarcoma 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 IV (day 3/ each cycle), followed by maintenance nivolumab for one year. The primary endpoint was the determination of the recommended phase II dose (RP2D). Sixteen patients were enrolled with no dose-limiting toxicities observed; the RP2D was established at full-dose epirubicin, ifosfamide, and nivolumab 360 mg. Grade 3-4 treatment-related adverse events included neutropenia (62.5%) and anemia (43.8%). The ORR was 68.8%, with 94% of patients experiencing tumor shrinkage. Median PFS was 9.9 months (95% CI, 7.0-12.7), and median OS was not reached. The combination of epirubicin, ifosfamide, and nivolumab is a safe, feasible, and highly active treatment for advanced UPS.