eUpdate – Medullary Thyroid Cancer Treatment Recommendations

Published: 19 February 2018. Authors: ESMO Guidelines Committee

Clinical Practice Guidelines

This update refers to Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Pacini F, Castagna MG, Brilli L, Pentheroudakis G. Ann Oncol 2012; 23 (Suppl 7):vii110-vii119.


Management of advanced/metastatic disease

Text update

In the randomised, double-blind, placebo-controlled, phase III study (ZETA), 331 patients with locally advanced or metastatic medullary thyroid cancer (MTC) were randomised in a 2:1 ratio to receive oral vandetanib or placebo until disease progression. A significant prolongation of PFS (primary end point) was observed for patients receiving vandetanib (hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.31–0.69; p<.001). Median PFS was 19.3 months in the placebo group while it had not yet been reached for the vandetanib group (predicted median PFS by Weibull model: 30.5 months). Overall survival data were immature. Common adverse events (any grade) occurred more frequently with vandetanib. 


In patients with unresectable locally advanced or metastatic, hereditary or sporadic MTC, vandetanib, as compared with placebo, is associated with a statistically and clinically significant improvement in PFS. In the absence of mature OS and quality of life data, the observed PFS benefit is associated with an ESMO-Magnitude of Clinical Benefit Scale (MCBS) score of 3.

ESMO-Magnitude of Clinical Benefit Scale (ESMO-MCBS) table for new therapies/indications in medullary thyroid cancer (MTC)*

Therapy Disease setting Trial Control Absolute survival gain HR (95% CI) Toxicity/Qol MCBS score**
Vandetanib (TKI targeting RET, VEGFR-2 and EGFR) Unresectable locally advanced or metastatic hereditary or sporadic medullary thyroid cancer

Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial [1]

Phase III


Median PFS: 19.3 months
PFS gain: 11.2 months PFS HR: 0.46 (0.31-0.69) Deteriorated toxicity profile

3 (Form 2b)

Mature data on OS not available

Data on QoL assessment not available

Patients receiving vandetanib experienced a statistically significant delay in time to worsening of pain compared with those receiving placebo

*EMA approvals since 1st January 2016
**ESMO-MCBS version 1.1 [2]
HR, hazard ratio; CI, confidence interval; QoL, quality of life; TKI, tyrosine kinase inhibitor; RET, rearranged during transfection proto-oncogene; VEGFR-2, vascular endothelial growth factor receptor 2; EGFR, epidermal growth factor receptor; PFS, progression-free survival; OS, overall survival; EMA, European Medicines Agency.


  1. Samuel A. Wells Jr, Bruce G. Robinson, Robert F. Gagel et al. Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial, J Clin Oncol 2012; 30; 134-141.
  2. Cherny NI, Dafni U, Bogaerts J et al. ESMO-Magnitude of Clinical Benefit Scale Version 1.1. Ann Oncol 2017; 28: 2340-2366.