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

  • Victor Manuel Villalobos
  • Francis Hall
  • Antonio Jimeno
  • Lia Gore
  • Kenneth Kern
  • Rossano Cesari
  • Bo Huang
  • Jeffrey T. Schowinsky
  • Patrick Judson Blatchford
  • Brianna Hoffner
  • Anthony Elias
  • Wells Messersmith
Bone and Soft Tissue Sarcomas

Abstract

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.

Notes

Acknowledgment

This clinical study was sponsored by Pfizer Inc.

Disclosure

Victor Manuel Villalobos, Francis Hall, Antonio Jimeno, Lia Gore, Kenneth Kern, Rossano Cesari, Bo Huang, Jeffrey T. Schowinsky, Patrick Judson Blatchford, Brianna Hoffner, Anthony Elias, Wells Messersmith have nothing disclosures to declare.

Supplementary material

10434_2017_6082_MOESM1_ESM.tiff (85 kb)
Supplementary Figure 1Progression Free Survival of desmoid patients on PF-03084014 (TIFF 85 kb)
10434_2017_6082_MOESM2_ESM.tiff (161 kb)
Supplementary Table 1Baseline characteristics information (TIFF 161 kb)

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Copyright information

© Society of Surgical Oncology 2017

Authors and Affiliations

  • Victor Manuel Villalobos
    • 1
  • Francis Hall
    • 2
  • Antonio Jimeno
    • 1
  • Lia Gore
    • 1
  • Kenneth Kern
    • 3
  • Rossano Cesari
    • 4
  • Bo Huang
    • 3
  • Jeffrey T. Schowinsky
    • 5
  • Patrick Judson Blatchford
    • 1
  • Brianna Hoffner
    • 1
  • Anthony Elias
    • 1
  • Wells Messersmith
    • 1
  1. 1.Division of Medical OncologyUniversity of Colorado Denver School of Medicine – Anschutz Medical CampusAuroraUSA
  2. 2.Division of Internal MedicineUniversity of Colorado Denver School of Medicine – Anschutz Medical CampusAuroraUSA
  3. 3.Pfizer Global Research and DevelopmentGrotonUSA
  4. 4.Pfizer OncologyMilanItaly
  5. 5.Department of PathologyUniversity of Colorado Denver School of Medicine – Anschutz Medical CampusAuroraUSA

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