Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor

N Engl J Med. 2010 Oct 28;363(18):1727-33. doi: 10.1056/NEJMoa1007056.

Abstract

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation. These results support the dependence of ALK-rearranged tumors on ALK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.).

Publication types

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

MeSH terms

  • Abdominal Neoplasms / drug therapy*
  • Abdominal Neoplasms / genetics
  • Adult
  • Anaplastic Lymphoma Kinase
  • Crizotinib
  • Granuloma, Plasma Cell / drug therapy*
  • Granuloma, Plasma Cell / genetics
  • Humans
  • Male
  • Mutation
  • Neoplasms, Muscle Tissue / drug therapy*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyridines / adverse effects
  • Pyridines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Growth Factor / antagonists & inhibitors
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Receptors, Growth Factor
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • MET protein, human
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases

Associated data

  • ClinicalTrials.gov/NCT00585195