, Volume 62, Issue 1, pp 46–56 | Cite as

The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer: a single-center, open-label, phase II, proof-of-concept study

  • Antongiulio Faggiano
  • Roberta Modica
  • Rosa Severino
  • Luigi Camera
  • Rosa Fonti
  • Michela Del Prete
  • Maria Grazia Chiofalo
  • Massimo Aria
  • Piero Ferolla
  • Giovanni Vitale
  • Luciano Pezzullo
  • Annamaria Colao
Endocrine Trials



Medullary thyroid cancer (MTC) is a neuroendocrine tumour of the thyroid C cells. Pasireotide, a multi-receptor targeted somatostatin analogue, and everolimus, an inhibitor of mTOR, showed antitumour properties in neuroendocrine tumours. Aim of this study was to evaluate pasireotide alone and in combination with everolimus in patients with MTC.


Patients with progressive metastatic or persistent postoperative MTC received pasireotide LAR 60 mg/m for at least 6 months. Patients exhibiting progressive disease received everolimus 10 mg/d as combination therapy. Primary endpoint was progression free survival (PFS). Secondary endpoints included, overall survival, objective response rates, change in circulating markers, safety. Study registration no. NCT01625520.


Nineteen consecutive patients were enrolled. Median follow-up was 31 months. Median PFS with pasireotide was 36 months (95% CI: 19.5–52.5). Nine patients (47%) had tumour progression: seven of them started everolimus in combination with pasireotide, achieving a median PFS of 9.0 months (95% CI: 0–21.83). Five of them (71%) had further tumour progression, one objective response (14.3%), one stopped treatment because of pulmonary embolism. Pasireotide alone and with everolimus was safe and required withdrawal only in one case. Diarrhoea and hyperglycaemia were the most frequent adverse events with pasireotide (grade 3 in 5.3% each). Hyperglycaemia was the most frequent grade 3 toxicity with the combination therapy (28.6%).


Pasireotide therapy shows antiproliferative effects in persistent postoperative MTC suggesting further investigation on larger series of patients. In progressive MTC lesions, the combination pasireotide plus everolimus may be of benefit. Both schemes were safe and well tolerated.


Medullary thyroid cancer Pasireotide Everolimus Neuroendocrine Tumours 


Author contributions

A.F.: conceived the study design and wrote the article. R.M., G.P., M.D.P., M.G.C., P.F.: collected clinical and biochemical data. L.C., R.S., R.F.: analyzed the radiological tumour response and wrote the part related to imaging. G.V., L.P.: proof-read the manuscript. A.C.: supervised the project

Compliance with ethical standards

Conflict of interest

A. Faggiano and A. Colao Department received grant for research from Novartis. The remaining authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Antongiulio Faggiano
    • 1
  • Roberta Modica
    • 1
  • Rosa Severino
    • 2
  • Luigi Camera
    • 2
  • Rosa Fonti
    • 3
  • Michela Del Prete
    • 4
    • 5
  • Maria Grazia Chiofalo
    • 6
  • Massimo Aria
    • 7
  • Piero Ferolla
    • 8
  • Giovanni Vitale
    • 9
    • 10
  • Luciano Pezzullo
    • 6
  • Annamaria Colao
    • 1
  1. 1.Department of Clinical Medicine and SurgeryFederico II UniversityNaplesItaly
  2. 2.Department of Advanced Biomedical Sciences, Radiology, Section of Diagnostic ImagingUniversity “Federico II”NaplesItaly
  3. 3.Institute of Biostructures and Bioimages - National Research CouncilNaplesItaly
  4. 4.Department of Radiology and Nuclear Medicine, and Cancer Research CenterUniversité LavalQuebec CityCanada
  5. 5.Department of Medical Imaging, and Oncology Branch of Research Center, CHU de QuébecUniversité LavalQuebec City (QC)Canada
  6. 6.Thyroid and Parathyroid Surgery UnitIstituto Nazionale per lo studio e la cura dei tumori “Fondazione G. Pascale” - IRCCSNaplesItaly
  7. 7.Department of Economics and StatisticsUniversity Federico IINaplesItaly
  8. 8.Department of Medical Oncology, Multidisciplinary NET GroupUmbria Regional Cancer Network and University of PerugiaPerugiaItaly
  9. 9.Department of Clinical Sciences and Community Health (DISCCO)University of MilanMilanItaly
  10. 10.Laboratory of Endocrine and Metabolic ResearchIstituto Auxologico Italiano IRCCSMilanItaly

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