Background
Phase 3 RCT (GeDDiS) of 257 patients with locally advanced or metastatic soft-tissue sarcoma, Trojani grade 2-3, with disease progression and no prior chemotherapy for sarcoma or prior doxorubicin. Grading reflects tumor differentiation, mitotic count, and necrosis.
Interventions and follow up
Arm A: Doxorubicin 75 mg/m2 day 1 q3wk
Arm B: Gemcitabine 675 mg/m2 days 1 and 8 + docetaxel 75 mg/m2 day 8 q3wk
Primary endpoint: Proportion alive and progression-free at 24 weeks
Secondary endpoints: PFS, OS, ORR, toxicity
mFollow up: 22 mo
Arm B: Gemcitabine 675 mg/m2 days 1 and 8 + docetaxel 75 mg/m2 day 8 q3wk
Primary endpoint: Proportion alive and progression-free at 24 weeks
Secondary endpoints: PFS, OS, ORR, toxicity
mFollow up: 22 mo
Results
24-wk PFS: 46.3% vs 46.4% (doxorubicin vs gem/docetaxel)
mPFS: 23.3 wk vs 23.7 wk; HR 1.28, 95%CI 0.99-1.65
mOS: 76.3 wk vs 67.3 wk; HR 1.14, 95%CI 0.83-1.57, P=.41
mPFS: 23.3 wk vs 23.7 wk; HR 1.28, 95%CI 0.99-1.65
mOS: 76.3 wk vs 67.3 wk; HR 1.14, 95%CI 0.83-1.57, P=.41
Adverse events
Grade ≥3 hematologic: neutropenia 25% vs 20%, febrile neutropenia 21% vs 12%, anemia 8% vs 6%
Grade ≥3 non-hematologic: mucositis 14% vs 2%, fatigue 6% vs 14%, pain 8% vs 11%
Grade ≥3 non-hematologic: mucositis 14% vs 2%, fatigue 6% vs 14%, pain 8% vs 11%
Conclusions
Single-agent doxorubicin and gemcitabine/docetaxel produced similar progression-free and overall survival in first-line soft-tissue sarcoma; doxorubicin should remain the standard first-line treatment for most patients given comparable efficacy and a simpler, less toxic regimen.
Key Limitations
Heterogeneous histologic subtypes pooled; not powered to detect subtype-specific differences (e.g., gem/docetaxel activity in leiomyosarcoma). Open-label design and 24-week landmark primary endpoint.
Clinical Context
Reinforces ESMO guidance positioning single-agent anthracycline (doxorubicin) as the first-line standard for advanced soft-tissue sarcoma, with gemcitabine/docetaxel reserved as an alternative or later-line option.