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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)46-56
Number of pages11
JournalEndocrine
Volume62
Issue number1
DOIs
Publication statusPublished - Oct 2018

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Disease-Free Survival
Neuroendocrine Tumors
Hyperglycemia
Everolimus
Medullary Thyroid cancer
pasireotide
Somatostatin Receptors
Therapeutics
Pulmonary Embolism
Diarrhea
Neoplasms
Thyroid Gland
Safety
Survival

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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. / Faggiano, Antongiulio; Modica, Roberta; Severino, Rosa; Camera, Luigi; Fonti, Rosa; Del Prete, Michela; Chiofalo, Maria Grazia; Aria, Massimo; Ferolla, Piero; Vitale, Giovanni; Pezzullo, Luciano; Colao, Annamaria.

In: Endocrine, Vol. 62, No. 1, 10.2018, p. 46-56.

Research output: Contribution to journalArticle

Faggiano, Antongiulio ; Modica, Roberta ; Severino, Rosa ; Camera, Luigi ; Fonti, Rosa ; Del Prete, Michela ; Chiofalo, Maria Grazia ; Aria, Massimo ; Ferolla, Piero ; Vitale, Giovanni ; Pezzullo, Luciano ; Colao, Annamaria. / 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. In: Endocrine. 2018 ; Vol. 62, No. 1. pp. 46-56.
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abstract = "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.",
author = "Antongiulio Faggiano and Roberta Modica and Rosa Severino and Luigi Camera and Rosa Fonti and {Del Prete}, Michela and Chiofalo, {Maria Grazia} and Massimo Aria and Piero Ferolla and Giovanni Vitale and Luciano Pezzullo and Annamaria Colao",
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T1 - The antiproliferative effect of pasireotide LAR alone and in combination with everolimus in patients with medullary thyroid cancer

T2 - a single-center, open-label, phase II, proof-of-concept study

AU - Faggiano, Antongiulio

AU - Modica, Roberta

AU - Severino, Rosa

AU - Camera, Luigi

AU - Fonti, Rosa

AU - Del Prete, Michela

AU - Chiofalo, Maria Grazia

AU - Aria, Massimo

AU - Ferolla, Piero

AU - Vitale, Giovanni

AU - Pezzullo, Luciano

AU - Colao, Annamaria

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

U2 - 10.1007/s12020-018-1583-7

DO - 10.1007/s12020-018-1583-7

M3 - Article

C2 - 29572709

VL - 62

SP - 46

EP - 56

JO - Endocrine

JF - Endocrine

SN - 1355-008X

IS - 1

ER -