Systemic Therapy for Chondrosarcoma

Opinion statement Clinical trial enrollment should be actively encouraged in all patients diagnosed with advanced, surgically unresectable chondrosarcoma (CS) due to the lack of consensus treatment recommendations. In the absence of an appropriate clinical trial, treatments are determined based on histologic subtype of CS with consideration given to targetable mutations (i.e., IDH1). Conventional CS is inherently resistant to cytotoxic chemotherapy and patients may benefit from antiangiogenic therapy including off-label use of pazopanib. Individuals harboring an IDH1 mutation may derive clinical benefit from ivosidenib, an IDH1 inhibitor. Upon progression and with functional status permitting, alternative options include mTOR inhibitors (sirolimus, temsirolimus) or other tyrosine kinase inhibitors (dasatinib), though no clear sequencing data exists. For dedifferentiated CS, conventional chemotherapies with osteosarcoma-like regimens are upfront options although prospective data is limited with minimal overall benefit. Alternative treatment options include immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS, but questionable efficacy was observed in small sample sizes with either approach. In mesenchymal CS, treatment with Ewing sarcoma-like chemotherapy regimens may be considered, although data supporting its use is even more limited given its rarity.

Automated summary

Clinical trial enrollment should be actively encouraged in all patients diagnosed with advanced, surgically unresectable chondrosarcoma (CS) due to the lack of consensus treatment recommendations. Treatment options for CS vary depending on histologic subtype and targetable mutations. Conventional CS is resistant to cytotoxic chemotherapy, but antiangiogenic therapy and IDH1 inhibitors may be beneficial. Alternative options include mTOR inhibitors or other tyrosine kinase inhibitors, although sequencing data is lacking. Treatment for dedifferentiated CS involves chemotherapies, but immunotherapy with pembrolizumab or ivosidenib in IDH1-mutant, dedifferentiated CS has questionable efficacy. Mesenchymal CS may be treated with Ewing sarcoma-like chemotherapy regimens, but data supporting its use is limited.