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

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. 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%. 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%). The primary end-point was not reached. This sequence allows high liver response with HAET, and everolimus controls the extrahepatic disease. NCT01678664 (clinicaltrials.gov). •Hepatic arterial embolisation therapy (HAET) is the main treatment of neuroendocrine liver metastases.•This phase II study tested the combination of both treatments.•Everolimus can be safely administered after HAET.•The primary end-point (hepatic progression-free survival at 24 months of 50%) was not reached.•HAET allows high liver objective response rate, and everolimus controls the extrahepatic disease.