Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments

Cancer. 2014 Sep 1;120(17):2694-703. doi: 10.1002/cncr.28766. Epub 2014 May 20.


Background: In a previous phase 2 trial, axitinib was active and well tolerated in patients with advanced thyroid cancer. In this second phase 2 trial, the efficacy and safety of axitinib were evaluated further in this population, and pharmacokinetic/pharmacodynamic relationships and patient-reported outcomes were assessed.

Methods: Patients (N = 52) with metastatic or unresectable, locally advanced medullary or differentiated thyroid cancer that was refractory or not amenable to iodine-131 received a starting dose of axitinib 5 mg twice daily. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, pharmacokinetic parameters, and patient-reported outcomes assessed with the MD Anderson Symptom Inventory questionnaire.

Results: The overall ORR was 35% (18 partial responses), and 18 patients had stable disease for ≥16 weeks. The median PFS was 16.1 months, and the median OS was 27.2 months. All-causality, grade ≥3 adverse events (>5%) were fatigue, dyspnea, diarrhea, decreased weight, pain in extremity, hypertension, decreased appetite, palmar-plantar erythrodysesthesia, hypocalcemia, and myalgia. Patients who had greater axitinib exposure had a longer median PFS. Quality of life was maintained during treatment with axitinib, and no significant deterioration in symptoms or interference in daily life caused by symptoms, assessed on MD Anderson Symptom Inventory subscales, were observed.

Conclusions: Axitinib has activity and a manageable safety profile while maintaining quality of life, and it represents an additional treatment option for patients with advanced thyroid cancer.

Trial registration: NCT00389441.

Keywords: MD Anderson Symptom Inventory; axitinib; metastatic disease; pharmacodynamic; pharmacokinetic; quality of life; radioactive iodine-refractory; thyroid cancer; tyrosine kinase inhibitor.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Axitinib
  • Carcinoma, Papillary / drug therapy*
  • Carcinoma, Papillary / mortality
  • Carcinoma, Papillary / secondary
  • Diarrhea / chemically induced
  • Disease-Free Survival
  • Female
  • Humans
  • Imidazoles / adverse effects
  • Imidazoles / pharmacokinetics
  • Imidazoles / therapeutic use*
  • Indazoles / adverse effects
  • Indazoles / pharmacokinetics
  • Indazoles / therapeutic use*
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Quality of Life
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Treatment Outcome


  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Axitinib

Associated data