Efficacy and safety of Vandetanib for patients with advanced and progressive medullary thyroid cancer (MTC) as systemic treatment beyond first-line...

Date 21 October 2018
Event ESMO 2018 Congress
Session Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology
Topics Thyroid Cancer
Anticancer Agents
Presenter Jorge Hernando Cubero
Citation Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293
Authors J. Hernando Cubero1, E. Grande2, P. Jimenez Fonseca3, C. Villabona4, J.M. Trigo Perez5, J. Martinez Trufero6, I. Pajares Bernad7, C. Lopez8, T. Alonso9, J. Biarnes10, T. Ramón Y Cajal11, M. Duran12, J.J. Grau13, S. Arevalo Lobera14, R. Mesia Nin15, M. Llanos16, E. Dalmau Portulas17, C. Alvarez18, C. Zafon19, J. Capdevila Castillon1
  • 1Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 2Head Of Medical Oncology Department, MD Anderson Cancer Center Center Espana, 28033 - Madrid/ES
  • 3Medical Oncology, Hospital Universitario Central de Asturias, 33006 - Oviedo/ES
  • 4Medical Oncology, Hospital Universitario de Bellvitge, 08907 - Barcelona/ES
  • 5Medical Oncology, Hospital Universitario Virgen de la Victoria, 29010 - Málaga/ES
  • 6Medical Oncology Department, Hospital Miguel Servet, 50009 - Zaragoza/ES
  • 7Medical Oncology, Hospital Miguel Servet, 50009 - Zaragoza/ES
  • 8Medical Oncology, Marques de Valdecilla University Hospital, Santander/ES
  • 9Medical Oncology, Hospital Ramón y Cajal, 28034 - Madrid/ES
  • 10Medical Oncology, Hospital Universitario Doctor Josep Trueta, Gerona/ES
  • 11Breast Cancer, Hospital de la Santa Creu i Sant Pau, 08041 - Barcelona/ES
  • 12Medical Oncology, Hospital Universitario Rey Juan Carlos, Madrid/ES
  • 13Medical Oncology, Hospital Clinic y Provincial de Barcelona, 8036 - Barcelona/ES
  • 14Medical Oncology, Hospital Donostia, 20014 - San Sebastian/ES
  • 15Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 08916 - Badalona/ES
  • 16Medical Oncology, Hospital Universitario de Canarias, Santa Cruz de Tenerife/ES
  • 17Medical Oncology, Hospital de Sabadell Corporacis Parc Tauli, 8208 - Sabadell/ES
  • 18Medical Oncology, Hospital Universitario La Paz, Madrid/ES
  • 19Endocrinology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES



Vandetanib has demonstrated efficacy in advanced MTC in a large phase III trial (ZETA trial, JCO 2012). However, the study had several limitations that impact in the daily clinical practice, such as the efficacy in patients (pts) with documented disease progression or beyond first-line therapy who have a worse prognosis.


Pts with advanced unresectable MTC with previous radiologically documented disease progression were included in the Spanish National Database of the Rare Cancer Working Group (GETHI). Pts started treatment with vandetanib 300mg qd as initial dose, with dose reductions allowed as per toxicity. Baseline characteristics, progression free survival (PFS), response rate (RR), correlation with biomarkers and toxicity data were reviewed retrospectively in first, second and third line setting. The program was validated by regulatory authorities and all patients signed and informed consent form.


59 pts (med age:48y; male 61%) were included. 14% had RET mutations. Vandetanib was given as first line in 61%, second-line in 22% and third-line therapy in 17% of pts. RR and median PFS in first, second and third-lines were 47%, 53% and 40% (p 0.85%) and 16.8, 13.6 and 11.5 months (p 0.94) respectively. No correlation was found between calcitonin or CEA reduction and RR. However, CEA level decrease (30% versus baseline) appeared to predict PFS longer than 11 months (p 0.028). Treatment was well tolerated and dose reduction was needed in 23% to handle toxicity. Main side effects were grade 1-2 including fatigue (22%), skin rash (19%), hypertension (14%) and diarrhea (14%). Most frequent grade 3 toxicity was oral mucositis (3%).


Probability of tumor shrinkage with vandetanib is maintained throughout treatment lines despite of a trend of reduced benefit in PFS beyond first-line in a cohort of pts with a worse prognosis. CEA reduction may predict longer PFS. Safety is maintained regardless prognosis and prior therapies.

Clinical trial identification

Legal entity responsible for the study

Spanish Rare Cancer Working Group (GETHI).


Has not received any funding.

Editorial Acknowledgement


All authors have declared no conflicts of interest.