Pan-cancer efficacy of pralsetinib in patients with RET fusion-positive solid tumors from the phase 1/2 ARROW trial

Nat Med. 2022 Aug;28(8):1640-1645. doi: 10.1038/s41591-022-01931-y. Epub 2022 Aug 12.


Oncogenic RET fusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW ( NCT03037385 , ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RET fusion-positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RET fusion partners in 23 efficacy-evaluable patients were CCDC6 (26%), KIF5B (26%) and NCOA4 (13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35-77) among these patients. Responses were observed regardless of tumor type or RET fusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib's potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion-positive solid tumors.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Fusion
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Neoplasms* / pathology
  • Proto-Oncogene Proteins c-ret / genetics
  • Pyrazoles* / adverse effects
  • Pyridines* / adverse effects
  • Pyrimidines* / adverse effects


  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • pralsetinib
  • Proto-Oncogene Proteins c-ret
  • RET protein, human

Associated data