The Desmoid Tumor Research Foundation

September 2017

Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor

Author Information

Villalobos VM(1), Hall F(2), Jimeno A(3), Gore L(3), Kern K(4), Cesari R(5), Huang B(4), Schowinsky JT(6), Blatchford PJ(3), Hoffner B(3), Elias A(3), Messersmith W(3)

(1)Division of Medical Oncology, University of Colorado Denver School of Medicine - Anschutz Medical Campus, Aurora, CO, USA.(2)Division of Internal Medicine, University of Colorado Denver School of Medicine - Anschutz Medical Campus, Aurora, CO, USA.(3)Division of Medical Oncology, University of Colorado Denver School of Medicine - Anschutz Medical Campus, Aurora, CO, USA.(4)Pfizer Global Research and Development, Groton, CT, USA.(5)Pfizer Oncology, Milan, Italy.(6)Department of Pathology, University of Colorado Denver School of Medicine - Anschutz Medical Campus, Aurora, CO, USA.

Publication

Ann Surg Oncol

Summary

We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0-96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5-21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation.

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