Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.
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.).
Butrynski
James E
JE
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
D'Adamo
David R
DR
Hornick
Jason L
JL
Dal Cin
Paola
P
Antonescu
Cristina R
CR
Jhanwar
Suresh C
SC
Ladanyi
Marc
M
Capelletti
Marzia
M
Rodig
Scott J
SJ
Ramaiya
Nikhil
N
Kwak
Eunice L
EL
Clark
Jeffrey W
JW
Wilner
Keith D
KD
Christensen
James G
JG
Jänne
Pasi A
PA
Maki
Robert G
RG
Demetri
George D
GD
Shapiro
Geoffrey I
GI
D000008:Abdominal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000077547:Crizotinib; D006104:Granuloma, Plasma Cell / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D009379:Neoplasms, Muscle Tissue / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D055815:Young Adult
D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D017978:Receptors, Growth Factor; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C491743:MET protein, human; D011505:Protein-Tyrosine Kinases; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases