Impact of tissue-agnostic approvals for patients with sarcoma

Tissue-agnostic drug development is a major step forward in offering treatment options for rare tumors. Sarcomas are heterogeneous rare malignancies with more than 100 subtypes. Recent failure of Phase III trials, nonbiomarker-driven clinical trials, and rarity hamper developmental therapeutics in sarcomas. Since a 'one-size-fits-all' approach continues to be the standard of care, tissue-agnostic approvals assume significance in sarcomas. In this review, we focus on the clinical evidence of recent drug approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) phenotype, and tumor mutation burden-high (TMB-H) status in the context of sarcomas, and the future landscape of tissueagnostic targets, such as rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).

Automated summary

Tissue-agnostic drug development provides new treatment options for rare tumors, but challenges remain due to heterogeneous nature and failed clinical trials in sarcomas. Approvals for neurotrophic tyrosine receptor kinase (NTRK) fusion, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) phenotype, and tumor mutation burden-high (TMB-H) status are particularly important in sarcomas. Future research may focus on tissue-agnostic targets such as rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).