Outcomes of Children and Adolescents with Advanced Hereditary Medullary Thyroid Carcinoma Treated with Vandetanib

Clin Cancer Res. 2018 Feb 15;24(4):753-765. doi: 10.1158/1078-0432.CCR-17-2101. Epub 2017 Nov 29.


Purpose: Vandetanib is well-tolerated in patients with advanced medullary thyroid carcinoma (MTC). Long-term outcomes and mechanisms of MTC progression have not been reported previously.Experimental Design: We monitored toxicities and disease status in patients taking vandetanib for hereditary, advanced MTC. Tumor samples were analyzed for molecular mechanisms of disease progression.Results: Seventeen patients [8 male, age 13 (9-17)* years] enrolled; 16 had a RET p.Met918Thr germline mutation. The duration of vandetanib therapy was 6.1 (0.1-9.7+)* years with treatment ongoing in 9 patients. Best response was partial response in 10, stable disease in 6, and progressive disease in one patient. Duration of response was 7.4 (0.6-8.7+)* and 4.9 (0.6-7.8+)* years in patients with PR and SD, respectively. Six patients died 2.0 (0.4-5.7)* years after progression. Median progression-free survival (PFS) was 6.7 years [95% confidence interval (CI): 2.3 years-undefined] and 5-year overall survival (OS) was 88.2% (95% CI: 60.6%-96.9%). Of 16 patients with a RET p.Met918Thr mutation, progression-free survival was 6.7 years (95% CI: 3.1-undefined) and 5-year overall survival was 93.8% (95% CI: 63.2%-99.1%). No patients terminated treatment because of toxicity. DNA sequencing of tissue samples (n = 11) identified an increase in copy number alterations across the genome as a potential mechanism of drug resistance [*median (range)].Conclusions: This study demonstrates that vandetanib is safe and results in sustained responses in children and adolescents with hereditary MTC. Our preliminary molecular data suggest that an increase in copy number abnormalities may be associated with tumor progression in hereditary MTC patients treated with vandetanib. Clin Cancer Res; 24(4); 753-65. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Carcinoma, Medullary / congenital*
  • Carcinoma, Medullary / drug therapy
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Child
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Multiple Endocrine Neoplasia Type 2a / drug therapy*
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Outcome Assessment, Health Care
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use*
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology


  • Piperidines
  • Protein Kinase Inhibitors
  • Quinazolines
  • N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine

Supplementary concepts

  • Familial medullary thyroid carcinoma