Advanced Soft-Tissue Sarcoma: Systemic Therapy

Advanced Soft-Tissue Sarcoma: overview

This algorithm organizes systemic therapy for advanced soft-tissue sarcoma by histologic subtype and line of therapy. In the first line, most subtypes receive an anthracycline-based regimen, doxorubicin with or without ifosfamide, linked to EORTC 62012; that trial showed that adding ifosfamide improved response rate and progression-free survival but not overall survival, so doxorubicin alone remains an appropriate standard for many patients. For leiomyosarcoma and undifferentiated pleomorphic sarcoma, gemcitabine plus docetaxel is shown as a first-line doublet (GeDDiS).

Second-line choices are subtype-specific. Liposarcoma is treated with trabectedin or eribulin, leiomyosarcoma in later lines with trabectedin (studied against dacarbazine), and non-adipocytic sarcomas with pazopanib, based on PALETTE, which improved progression-free survival versus placebo in pretreated disease without a significant overall survival benefit. For multiply refractory disease, the chart lists regorafenib (REGOSARC) as an antiangiogenic option and subtype-directed clinical trials.

Trials behind this algorithm

• EORTC 62012 Judson I et al, Lancet Oncol, 2014; PMID: 24618336
• Eribulin vs dacarbazine liposarcoma Schoffski P et al, 2016, Lancet. PMID: 26874885
• Trabectedin vs Dacarbazine in liposarcoma Demetri, GD et al, 2016, JCO, PMID: 26371143
• PALETTE Van der Graaf WT et al, Lancet, 2012; PMID: 22595799

Background reading: Sarcomas board review notes.