Phase 2 study of vascular endothelial growth factor trap for the treatment of metastatic thyroid cancer Journal Article


Authors: Sherman, E. J.; Dunn, L. A.; Schöder, H.; Ho, A. L.; Baxi, S. S.; Ghossein, R. A.; Haque, S. S.; Sima, C.; Tuttle, R. M.; Pfister, D. G.
Article Title: Phase 2 study of vascular endothelial growth factor trap for the treatment of metastatic thyroid cancer
Abstract: Background: Several multitargeted tyrosine kinase inhibitors (TKIs) have demonstrated activity in patients with thyroid cancer that is refractory to radioactive iodine (RAI). The antitumor effect is attributed at least in part to the ability of these TKIs to inhibit angiogenesis in these vascular tumors. Vascular endothelial growth factor (VEGF) Trap (VT) is a recombinantly produced fusion protein consisting solely of human sequences for VEGF receptors 1 and 2 extracellular domains and human immunoglobulin 1. Evaluating VT in patients with thyroid cancer is reasonable considering the activity observed with TKIs targeting VEGF. Methods: The current study was a single-institution, phase 2, Simon 2-stage design (21 to >41 patients) study based on the objective response rate and/or 6-month progression-free survival as the primary endpoints. Eligible patients were required to have progressive, RAI-refractory and/or [18F]fludeoxyglucose-avid, recurrent and/or metastatic, nonmedullary, nonanaplastic thyroid cancer; disease that was measurable using Response Evaluation Criteria In Solid Tumors (RECIST) criteria; and adequate organ and bone marrow function. VT at a dose of 4 mg/kg intravenously was administered every 14 days. Results: A total of 40 patients were included in the analysis. Of these patients, 24 had papillary thyroid cancer, 2 had follicular thyroid cancer, and 11 had Hurthle cell thyroid cancer. The final 3 tumors were classified as poorly differentiated. There were no complete and/or partial responses noted; 34 patients achieved stable disease and 6 patients experienced disease progression as their best response. Of the 34 patients with stable disease, 16 remained on the study for >6 months and 6 patients remained on the study for >12 months. The median duration on treatment was 4.1 months (range, 0.6-30.8 months). Conclusions: Unlike TKIs, which have shown responses in this setting, to the authors’ knowledge there have been no responses observed with the use of single-agent VT to date. It does not appear to be a promising drug for the treatment of patients with thyroid cancer. © 2019 American Cancer Society
Keywords: thyroid cancer; phase 2; radioactive iodine (rai)-refractory; vascular endothelial growth factor receptor (vegf) trap
Journal Title: Cancer
Volume: 125
Issue: 17
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2019-09-01
Start Page: 2984
End Page: 2990
Language: English
DOI: 10.1002/cncr.32046
PUBMED: 31174237
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 30 August 2019 -- Source: Scopus
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MSK Authors
  1. Camelia S Sima
    206 Sima
  2. Ronald A Ghossein
    315 Ghossein
  3. Robert M Tuttle
    368 Tuttle
  4. Eric J Sherman
    159 Sherman
  5. Heiko Schoder
    305 Schoder
  6. Sofia S Haque
    88 Haque
  7. David G Pfister
    262 Pfister
  8. Shrujal S Baxi
    76 Baxi
  9. Alan Loh Ho
    91 Ho
  10. Lara   Dunn
    35 Dunn