Impact of KIT exon 10 M541L allelic variant on the response to imatinib in aggressive fibromatosis: analysis of the desminib series by competitive allele specific Taqman PCR technology.

Abstract

BACKGROUND:

Aggressive fibromatosis (AF) is a rare fibroblastic proliferative disease with a locally aggressive behavior and no distant metastasis, characterized by driver mutations in CTNNB1 or the APC gene. When progressive and/or symptomatic AF is not amenable to local management, a variety of medical treatments may be efficient, including imatinib mesylate. The phase II "Desminib trial" included 40 patients with AF to evaluate the toxicity and efficacy of imatinib resulting in a 65% tumor control rate at 1 year. We investigated a potential predictive value of KIT exon 10 M541L variant (KITL541) on this prospective series.

METHODS:

DNA was extracted in sufficient quantity from 33 patients included in the Desminib trial. The detection of KITL541 was performed by Competitive Allele-Specific Taqman® PCR technology. Chi-2 analyses were performed to search for a correlation between KIT status and tumor response. Progression free (PFS) and overall survival (OS) were compared by log-rank test after Kaplan-Meier analysis.

RESULTS:

In 6 out of 33 cases (18%), the technique failed to determine the mutational status; 5 patients (19%) harboured KITL541 and 22 patients (81%) were classified as KIT wild type. Compared with total cohort, KITL541 frequency did not distinguish between different clinical characteristics. In the KITL541 and the KITWT subgroups, the tumor control rate at 1 year was 100% and 68%, respectively (p = 0.316). The median PFS of patients harboring KITL541 or not is 29.9 and 24.5 months, respectively (p = 0.616), and the median OS is not reached, in any of the groups.

CONCLUSION:

Our results do not support a predictive effect of KITL541 on the efficacy of imatinib for patients with AF.

• Authors: Armelle Dufresne, Laurent Alberti, Mehdi Brahmi, Sarah Kabani, Héloïse Philippon, David Pérol, Jean Yves Blay
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 632 (Aug 29 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25174682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate
• Proto-Oncogene Proteins c-kit

Topics

• Adult
• Aged
• Benzamides (administration & dosage, therapeutic use)
• Clinical Trials, Phase II as Topic
• Female
• Fibromatosis, Aggressive (drug therapy, genetics, pathology)
• Genetic Variation
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Piperazines (administration & dosage, therapeutic use)
• Polymerase Chain Reaction (methods)
• Prospective Studies
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)
• Proto-Oncogene Proteins c-kit (genetics)
• Pyrimidines (administration & dosage, therapeutic use)
• Survival Analysis
• Treatment Outcome
• Young Adult