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

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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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.

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Authors and Affiliations

  1. Division of Medical Oncology, University of Colorado Denver School of Medicine – Anschutz Medical Campus, Aurora, CO, USA

    Victor Manuel Villalobos MD, PhD, Antonio Jimeno MD, PhD, Lia Gore MD, Patrick Judson Blatchford PhD, Brianna Hoffner MSN, ANP, Anthony Elias MD & Wells Messersmith MD

  2. Division of Internal Medicine, University of Colorado Denver School of Medicine – Anschutz Medical Campus, Aurora, CO, USA

    Francis Hall MD

  3. Pfizer Global Research and Development, Groton, CT, USA

    Kenneth Kern MD, MPH, MS & Bo Huang PhD

  4. Pfizer Oncology, Milan, Italy

    Rossano Cesari PhD

  5. Department of Pathology, University of Colorado Denver School of Medicine – Anschutz Medical Campus, Aurora, CO, USA

    Jeffrey T. Schowinsky MD

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  1. Victor Manuel Villalobos MD, PhD
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  2. Francis Hall MD
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Corresponding author

Correspondence to Victor Manuel Villalobos MD, PhD.

Electronic supplementary material

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Supplementary Figure 1

Progression Free Survival of desmoid patients on PF-03084014 (TIFF 85 kb)

Supplementary Table 1

Baseline characteristics information (TIFF 161 kb)

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Villalobos, V.M., Hall, F., Jimeno, A. et al. Long-Term Follow-Up of Desmoid Fibromatosis Treated with PF-03084014, an Oral Gamma Secretase Inhibitor. Ann Surg Oncol 25, 768–775 (2018). https://doi.org/10.1245/s10434-017-6082-1

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  • DOI: https://doi.org/10.1245/s10434-017-6082-1

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