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

Ann Surg Oncol. 2018 Mar;25(3):768-775. doi: 10.1245/s10434-017-6082-1. Epub 2017 Sep 8.


Background: Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in β-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014.

Methods: 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. After cycle 9, patients were evaluated as clinically indicated.

Results: 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.

Conclusions: PF-03084014 was effective in treating desmoid tumors, with an objective response rate of 71.4% (95% CI 29.0-96.3%) in this small cohort of patients. 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors*
  • Fibromatosis, Aggressive / drug therapy*
  • Fibromatosis, Aggressive / enzymology
  • Fibromatosis, Aggressive / pathology
  • Follow-Up Studies
  • Humans
  • Prognosis
  • Retrospective Studies
  • Tetrahydronaphthalenes / administration & dosage*
  • Time Factors
  • Valine / administration & dosage
  • Valine / analogs & derivatives*


  • Tetrahydronaphthalenes
  • Amyloid Precursor Protein Secretases
  • Valine
  • nirogacestat