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(36 visite) Faggiano A, Modica R, Severino R, Camera L, Fonti R, Del Prete M, Chiofalo MG, Aria M, Ferolla P, Vitale G, Pezzullo L, Colao A
Impact factor: 3.179, Impact factor a 5 anni: 2.675
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Parole chiave: Everolimus, Medullary Thyroid Cancer, Neuroendocrine Tumours, Pasireotide,
*** IBB - CNR *** Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. firstname.lastname@example.org. Department of Advanced Biomedical Sciences, Radiology, Section of Diagnostic Imaging, University "Federico II", Naples, Italy. Institute of Biostructures and Bioimages - National Research Council, Naples, Italy. Department of Radiology and Nuclear Medicine, and Cancer Research Center, Universite Laval, Quebec City, Canada. Department of Medical Imaging, and Oncology Branch of Research Center, CHU de Quebec, Universite Laval, 11 cote du Palais, Quebec City (QC), G1R 2J6, Canada. Thyroid and Parathyroid Surgery Unit, Istituto Nazionale per lo studio e la cura dei tumori "Fondazione G. Pascale" - IRCCS, Naples, Italy. Department of Economics and Statistics, University Federico II, Naples, Italy. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
PURPOSE: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.<br>