Everolimus after hepatic arterial embolisation therapy of metastases from gastrointestinal neuroendocrine tumours: The FFCD 1104-EVACEL-GTE phase II study.

Abstract

BACKGROUND:

Hepatic arterial embolisation therapy (HAET) is a treatment of liver metastases of gastrointestinal neuroendocrine tumours (GI-NETs). HAET increases circulating vascular endothelial growth factor levels. Everolimus is a treatment in NETs that may have antiangiogenic activity.

METHODS:

This phase II study was conducted in patients with predominant and progressive liver metastases from GI-NETs. Everolimus was initiated 7-30 days after HAET. The hypothesis was that everolimus after HAET would increase hepatic progression-free survival (hPFS) rate at 24 months from 35% to 50%.

RESULTS:

Among the 74 patients included, 88% had small-bowel primary tumour, 43% had grade I and 57% grade II tumour, and 51% had extrahepatic metastases. Patients underwent one (n = 19), two (n = 54), or three (n = 1) HAET procedures. hPFS at 24 months was 33% (95% confidence interval [CI], 22.5-43.7); 40 (54%) patients had objective response. Median (95% CI) hPFS, PFS, and overall survival were 19 (14-23), 17 (13-22), and 51 (33-60) months. The most common grade III-IV toxicities (>5%) in patients receiving both HAET and everolimus (n = 67) were elevated liver enzymes (55%), fatigue (18%), diarrhoea (16%), anaemia (12%), hypertriglyceridaemia (7%) and mucositis (6%).

CONCLUSIONS:

The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease.

TRIAL REGISTRATION:

NCT01678664 (clinicaltrials.gov).

• Authors: Thomas Walter, Come Lepage, Romain Coriat, Emilie Barbier, Guillaume Cadiot, Francois-Xavier Caroli-Bosc, Thomas Aparicio, Karine Bouhier-Leporrier, Olivia Hentic-Dhome, Frédérique Gay, Anne-Claire Dupont-Gossart, Muriel Duluc, Céline Lepere, Thierry Lecomte, Denis Smith, Caroline Petorin, Frédéric Di-Fiore, Francois Ghiringhelli, Jean-Louis Legoux, Rosine Guimbaud, Eric Baudin, Catherine Lombard-Bohas, Thierry de Baère, FFCD 1104 investigators/investigators
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 123 Pg. 92-100 (12 2019) ISSN: 1879-0852 [Electronic] England
• PMID: 31678771 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Antibiotics, Antineoplastic
• Antineoplastic Agents
• Streptozocin
• Doxorubicin
• Everolimus

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibiotics, Antineoplastic (administration & dosage)
• Antineoplastic Agents (therapeutic use)
• Bone Neoplasms (drug therapy, secondary)
• Chemoembolization, Therapeutic
• Doxorubicin (administration & dosage)
• Embolization, Therapeutic
• Everolimus (therapeutic use)
• Female
• Gastrointestinal Neoplasms (pathology)
• Hepatic Artery
• Humans
• Liver Neoplasms (secondary, therapy)
• Lung Neoplasms (drug therapy, secondary)
• Lymph Nodes (pathology)
• Male
• Middle Aged
• Neuroendocrine Tumors (secondary, therapy)
• Peritoneal Neoplasms (drug therapy, secondary)
• Progression-Free Survival
• Streptozocin (administration & dosage)