Overview of Soft Tissue Sarcoma Treatment
Soft tissue sarcomas are a heterogeneous group of over 50 histologic subtypes requiring subtype-specific treatment approaches. Doxorubicin remains the standard first-line systemic therapy. Trabectedin and pazopanib provide second-line options. Eribulin has demonstrated benefit in liposarcoma. Tazemetostat (Tazverik) is approved specifically for epithelioid sarcoma as the first EZH2 inhibitor.
Treatment by Setting
First-Line Advanced STS
- Doxorubicin ± ifosfamide
- Gemcitabine + docetaxel (leiomyosarcoma)
Second-Line and Beyond
- Trabectedin (Yondelis) — especially L-sarcomas
- Pazopanib (Votrient) — non-adipocytic STS
- Eribulin (Halaven) — liposarcoma
Subtype-Specific
- Tazemetostat (Tazverik) — epithelioid sarcoma
Epidemiology & Impact
Soft tissue sarcomas comprise over 70 subtypes from mesenchymal tissues with approximately 13,590 cases and 5,200 deaths annually. They account for less than 1% of adult cancers. Common subtypes include UPS, liposarcoma, leiomyosarcoma, and synovial sarcoma. Approximately 60% arise in extremities. Five-year survival is approximately 65%.
Molecular Biology & Biomarkers
Highly subtype-specific. Translocation-driven: synovial sarcoma (SS18-SSX), myxoid liposarcoma (FUS-DDIT3), DFSP (COL1A1-PDGFB). Amplification-driven: well-differentiated liposarcoma (MDM2). Complex karyotype: leiomyosarcoma, UPS. Molecular diversity makes trial design challenging.
Evolving Treatment Landscape
Surgery with wide margins is cornerstone. Doxorubicin-based chemotherapy is first-line for advanced disease. Subtype-specific advances include tazemetostat for INI1-negative epithelioid sarcoma, avapritinib for PDGFRA-mutant GIST, imatinib for DFSP. Immunotherapy shows activity mainly in UPS and alveolar soft part sarcoma.
Approved Therapies
Frequently Asked Questions
FAQWhy is sarcoma complex?
Over 70 subtypes with different molecular drivers and treatment sensitivities requiring subtype-specific diagnosis and management.
What is molecular testing's role?
Critical for accurate diagnosis (specific translocations confirm subtypes) and identifying actionable targets (INI1 loss, NTRK fusions).
When is immunotherapy useful?
Meaningful activity mainly in UPS and alveolar soft part sarcoma; most STS subtypes show limited response.
Active Clinical Trials
PHASE 3 Late-Stage Pivotal Trials
ANNOUNCE
Drug: Nirogacestat (gamma-secretase inhibitor)
Population: Progressive desmoid tumor/aggressive fibromatosis
Status: Published - FDA Approved Nov 2023 | NCT03785964 ↗
Search for additional trials on ClinicalTrials.gov ↗
PHASE 2 Efficacy and Safety Studies
TRK Inhibitors
Drugs: Larotrectinib, Entrectinib
Target: NTRK fusion-positive sarcomas
Search for additional trials on ClinicalTrials.gov ↗
PHASE 1 First-in-Human Dose-Finding Studies
Phase 1 trials establish safety profiles and determine recommended doses for novel anticancer agents in early-stage development.
Search for active Phase 1 trials on ClinicalTrials.gov ↗
Find Clinical Trials Near You
Interested in participating in a clinical trial? Visit ClinicalTrials.gov to search for trials by location, cancer type, and eligibility criteria. Discuss options with your oncologist to determine if clinical trial participation is appropriate for you.
Search ClinicalTrials.gov →🇪🇺 EU Clinical Pipeline (EudraCT Trials)
Active clinical trials registered in EU Clinical Trials Register
Phase 3 Trials
Late-stage European confirmatory trials
Phase 2 Trials
Mid-stage European efficacy trials
Phase 1 Trials
Early-stage European safety trials