Impact of tissue-agnostic approvals for patients with sarcoma

Trends Cancer. 2022 Feb;8(2):135-144. doi: 10.1016/j.trecan.2021.11.007. Epub 2021 Dec 6.

Abstract

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 tissue-agnostic targets, such as rearranged during transfection (RET), fibroblast growth factor receptor (FGFR), and neuregulin-1 (NRG1).

Keywords: MSI-H; NTRK; RET; TMB-H; biomarker; genomics; histology-agnostic; sarcoma; tissue-agnostic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Gene Fusion
  • Humans
  • Microsatellite Instability
  • Receptor Protein-Tyrosine Kinases / genetics
  • Sarcoma* / diagnosis
  • Sarcoma* / drug therapy
  • Sarcoma* / genetics

Substances

  • Biomarkers, Tumor
  • Receptor Protein-Tyrosine Kinases