Canadian consensus on TRK-inhibitor therapy for NTRK fusion-positive sarcoma

Int J Cancer. 2021 Nov 1;149(9):1691-1704. doi: 10.1002/ijc.33723. Epub 2021 Aug 4.

Abstract

Malignant sarcomas are rare accounting for <1% of all adult solid malignancies and approximately 11% to 13% of all pediatric malignancies. TRK-inhibitors have demonstrated robust and long-lasting responses in patients with NTRK fusion-positive solid tumors, including sarcoma. Access to these agents in many jurisdictions such as Canada remains limited. We undertook a modified Delphi consensus to articulate and convey the clinical importance of these agents for the Canadian sarcoma community. A systematic search of published and presented literature was conducted to identify clinical trials reporting outcomes on the use of TRK-inhibitors in relapsed/refractory NTRK fusion-positive sarcoma. Three main consensus questions were identified: (a) is there currently an unmet clinical need for systemic therapy options in relapsed/refractory sarcoma? (b) do TRK-inhibitors confer a clinical benefit to patients with NTRK fusion-positive sarcoma? (c) do phase I/II basket trials provide sufficient evidence to justify funding of TRK-inhibitors in NTRK fusion-positive sarcoma? Response rates to the first and second surveys were 57% (n = 30) and 42% (n = 22), respectively. There was strong agreement among the Canadian sarcoma community that there was unmet clinical need for effective systemic therapy options in relapsed/refractory sarcoma, that TRK-inhibitors are a safe and effective treatment option for patients with NTRK fusion-positive sarcoma, and that available phase I/II basket trials provide sufficient evidence to support funding of these agents in relapsed/refractory NTRK fusion-positive sarcoma. TRK-inhibitors are a safe and effective systemic therapy option for patients with relapsed/refractory NTRK fusion-positive sarcoma.

Keywords: NTRK fusion-positive; TRK-inhibitor; consensus; sarcoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Canada
  • Consensus
  • Disease Progression
  • Humans
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, trkA / genetics
  • Receptor, trkA / metabolism*
  • Receptor, trkC / antagonists & inhibitors*
  • Receptor, trkC / genetics
  • Receptor, trkC / metabolism
  • Sarcoma / drug therapy*
  • Sarcoma / genetics
  • Sarcoma / metabolism
  • Surveys and Questionnaires / statistics & numerical data*
  • Survival Analysis
  • Young Adult

Substances

  • Oncogene Proteins, Fusion
  • Protein Kinase Inhibitors
  • Receptor, trkA
  • Receptor, trkC