Epirubicin/Ifosfamide + Nivolumab Hits 69% ORR in First-Line Undifferentiated Pleomorphic Sarcoma

Epirubicin (anthracycline; 60 mg/m² d1-2) and ifosfamide (3 g/m² d1-3) paired with the PD-1 inhibitor nivolumab (360 mg d3) were tested in 3-week cycles in the Spanish phase Ib ImmunoSarc2 cohort 7a (NCT03277924). Among 16 previously untreated metastatic UPS patients (median age 56; ECOG 0-1), investigator-assessed ORR reached 68.8% (1 CR, 10 PRs) with 93.8% disease control. With a median follow-up of 16.3 months, the median PFS was 9.9 months (95% CI 7.0-12.7) and the median overall survival was not reached. The OS rate after one year was 81%. Grade 3-4 toxicities were chiefly hematologic—neutropenia 62.5%, anemia 31%, thrombocytopenia 25%—with one treatment-related fatal hemorrhage; only one cycle-1 DLT occurred and no dose reductions were needed. By contrast, the anthracycline/ifosfamide standard (EORTC 62012) posts ~26% ORR, median PFS 7.4 months, and similar but slightly lower ≥G3 myelosuppression.