Motesanib diphosphate in progressive differentiated thyroid cancer

N Engl J Med. 2008 Jul 3;359(1):31-42. doi: 10.1056/NEJMoa075853.

Abstract

Background: The expression of vascular endothelial growth factor (VEGF) is characteristic of differentiated thyroid cancer and is associated with aggressive tumor behavior and a poor clinical outcome. Motesanib diphosphate (AMG 706) is a novel oral inhibitor of VEGF receptors, platelet-derived growth-factor receptor, and KIT.

Methods: In an open-label, single-group, phase 2 study, we treated 93 patients who had progressive, locally advanced or metastatic, radioiodine-resistant differentiated thyroid cancer with 125 mg of motesanib diphosphate, administered orally once daily. The primary end point was an objective response as assessed by an independent radiographic review. Additional end points included the duration of the response, progression-free survival, safety, and changes in serum thyroglobulin concentration.

Results: Of the 93 patients, 57 (61%) had papillary thyroid carcinoma. The objective response rate was 14%. Stable disease was achieved in 67% of the patients, and stable disease was maintained for 24 weeks or longer in 35%; 8% had progressive disease as the best response. The Kaplan-Meier estimate of the median duration of the response was 32 weeks (the lower limit of the 95% confidence interval [CI] was 24; the upper limit could not be estimated because of an insufficient number of events); the estimate of median progression-free survival was 40 weeks (95% CI, 32 to 50). Among the 75 patients in whom thyroglobulin analysis was performed, 81% had decreased serum thyroglobulin concentrations during treatment, as compared with baseline levels. The most common treatment-related adverse events were diarrhea (in 59% of the patients), hypertension (56%), fatigue (46%), and weight loss (40%).

Conclusions: Motesanib diphosphate can induce partial responses in patients with advanced or metastatic differentiated thyroid cancer that is progressive. (ClinicalTrials.gov number, NCT00121628.)

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / drug therapy
  • Adenocarcinoma, Follicular / secondary
  • Adenoma, Oxyphilic / drug therapy
  • Adenoma, Oxyphilic / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Papillary / drug therapy*
  • Carcinoma, Papillary / secondary
  • Female
  • Genotype
  • Humans
  • Indoles / adverse effects
  • Indoles / therapeutic use*
  • Male
  • Middle Aged
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Oligonucleotides
  • Proto-Oncogene Proteins c-kit
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Survival Analysis
  • Thyroglobulin / blood
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Indoles
  • Oligonucleotides
  • Niacinamide
  • Thyroglobulin
  • Proto-Oncogene Proteins c-kit
  • Receptors, Vascular Endothelial Growth Factor
  • imetelstat

Associated data

  • ClinicalTrials.gov/NCT00121628