Durvalumab (PD-L1) + doxorubicin boosts PFS to 8.2 mo in anthracycline-naïve soft-tissue sarcoma

Durvalumab, a PD-L1 inhibitor, 1500 mg plus topoisomerase II inhibitor doxorubicin 75 mg/m² Q3W was tested in the phase Ib/II NCT03798106 trial in 41 metastatic/recurrent STS patients with no prior anthracycline or PD-(L)1 therapy. ORR reached 31.7% (13/41); median PFS was 8.2 mo and median OS 24.1 mo. Genomic correlative work showed RTK/RAS alterations (HR 6.4) predicted shorter PFS, while high intratumoral PD-1 density (HR 0.21) correlated with longer benefit (16.9 mo vs 7.4 mo). Grade 3/4 toxicities were manageable, and no DLTs emerged. Historically, single-agent doxorubicin delivers ~14% ORR, 4.6 mo PFS, and ~12 mo OS in first-line advanced STS, underscoring a roughly two-fold gain in disease control with the chemo-IO pairing.