Identification of biological factors predictive of response to imatinib mesylate in aggressive fibromatosis

• Published in: British journal of cancer Vol. 103; no. 4; pp. 482 - 485
• Main Authors: Dufresne, A, Bertucci, F, Penel, N, Le Cesne, A, Bui, B, Tubiana-Hulin, M, Ray-Coquard, I, Cupissol, D, Chevreau, C, Perol, D, Goncalves, A, Jimenez, M, Bringuier, P P, Blay, J Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 10-08-2010; Nature Publishing Group
• Subjects: 692/53/2423; 692/699/67; 692/699/67/1059; Adult; Aged; Benzamides; Biomarkers, Tumor - analysis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Drug Resistance; Epidemiology; Female; Fibromatosis, Aggressive - drug therapy; Fibromatosis, Aggressive - therapy; Humans; Imatinib Mesylate; Immunohistochemistry; Male; Middle Aged; Molecular Medicine; Oncology; Piperazines; Prognosis; Proto-Oncogene Proteins c-kit - analysis; Pyrimidines; Translational Therapeutics; Treatment Outcome; Young Adult; imatinib mesylate; aggressive fibromatosis; predictive factors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6605783

Background:
Imatinib induces responses and disease stabilisations in non-resectable patients with aggressive fibromatosis (AF). The precise target of imatinib in AF and predictive factors for response to treatment are unknown.
Methods:
We investigated factors potentially predictive of response to imatinib in a series of 40 patients with progressive AF included in a phase II trial of imatinib: we tested the presence of
KIT
exon 10 variant (M541L), the expression of imatinib-sensitive kinases and cell cycle proteins by immunohistochemistry (IHC), and other clinical and biological factors.
Results:
Of 10 patients for whom DNA could be extracted, 3 had a
KIT
exon 10 variant (30%), with no correlation with response or progression-free survival (PFS). The expression of other imatinib targets (PDGFRA/B, macrophage colony-stimulating factor receptor (M-CSFR)) and of downstream components of the cell cycle, cell proliferation and proliferation pathway (cyclin D1, ERK, MEK 1–2) did not correlate with PFS. Pre-treatment lymphopenia (<1500/
μ
l) and tumour size >120 mm correlated with shorter PFS in univariate and multivariate analyses.
Conclusion:
Our findings show that a baseline biological characteristic of the patient is the major parameter influencing response to imatinib in aggressive fibromatosis. Tumour characteristics, including the presence of a KIT exon 10 M541L variant, may influence tumour control but this needs to be confirmed and better explained.