Transarterial liver therapy (TALT) is indicated in the treatment of isolated or predominant progressive liver metastases of gastrointestinal neuroendocrine tumors (GI-NETs). TALT increases circulating VEGF levels. Everolimus is an approved systemic treatment in NETs that has anti-angiogenic activities. Our hypothesis is that everolimus may increase hepatic progression-free survival (hPFS) 24 months after TALT.
EVACEL is a single arm phase II multicenter prospective study conducted in patients with predominant and progressive liver metastases within previous 12 months from well-differentiated grade 1-2 GI-NETs. Everolimus (10 mg/day) was started 7 days after TALT, once liver toxicity was grade ≤1. The primary endpoint was the hPFS rate at 24 months (≥35% is sufficient to demonstrate efficacy, 50% is expected) based on the central review assessment.
The characteristics of the 77 enrolled patients were female 42%, median age 66 (range: 43-86) years, primary tumor in the small bowel 91%, grade G1 43%, G2 57%, extra-hepatic metastases 51%), median liver tumor burden 30% (range, 1-80), and previous somatostatin analog treatment 74%. Patients underwent 1 (n = 19), 2 (n = 54) or 3 (n = 1) TALT: bland (n = 21) or chemo-embolization (n = 109). Sixty-seven (87%) pts were eligible for everolimus. Forty (54%) and 30 (41%) pts had objective response (RECIST 1.1) and stable disease, respectively (1 pt was not evaluable). Median (IC 95%) PFS and overall survival were 16.9 (12.6-22.3) and 44.6 (29.1-not reached) months, respectively. The most common grade 3-4 toxicities (>5%) in patients receiving both TALT and everolimus (n = 67) were the post-TALT syndrome (55%), fatigue (18%), diarrhea (16%), anemia (12%), cutaneous (9%), hypertriglyceridemia (7.5%) and mucositis (6%). The primary endpoint will be presented at the meeting.
Everolimus can be safely administered following TALT. Results of this sequence of therapies are encouraging.
Clinical trial identification
Legal entity responsible for the study
Novartis Pharma AG provided an unrestricted research grant.
T. Walter: Congress, advisory board, research: Novartis, Ipsen, Keocyt, AAA. C. Lepage: Research: Ipsen Pharma, Novartis Oncology; Speaker: Advanced Accelerator Applications; Travel, accomodations: Amgen, Ipsen Pharma, Novartis Oncology, Bayer. R. Coriat: Consulting or advisory role: Keocyt, Pfizer, Novartis, Roche, Merck, Amgen, Bayer; Research funding: Amgen, Novartis, Ipsen; Travel, accomodations, expenses: Ipsen, Amgen, Bayer. G. Cadiot: Honoraria: Ipsen, Novartis, Pfizer, AAA, Keocyt; Consulting or advisory role: Ipsen, Novartis, Pfizer, AAA, Keocyt; Research funding: Ipsen, Novartis. F.X. Caroli Bosc: Honoraria: Ipsen, Novartis, Lilly, Amgen. T. Aparicio: Honoraria: Shire, Roche, Servier, BMS, Amgen, Léo Pharma; Consulting or advisory role: BMS, Halio DX; Research funding: Novartis; Travel, accomodations, expenses: Roche, Hospira, Ipsen. K. Bouhier Leporrier: Honoraria, boards and congress: Ipsen and Novartis. C. Lepere: Consulting or advisory role: Novartis, Ipsen; Travel, accomodations, expenses: Ipsen, Novartis, Amgen. T. Lecomte: Consulting or advisory role, research funding, travel: Novartis; Consulting or advisory role, Travel: Ipsen. D. Smith: Speaker’s bureau: Novartis; Consulting or advisory role: Novartis, Pfizer. C. Petorin: Travel, accomodations, expenses: Novartis. M.P. Ducreux: Grants/research supports: Roche, Chugai, Pfizer; Honoraria or consultation fees: Roche, Celgene, Merck Serono, Amgen, Novartis, Sanofi, Pfizer, Lilly, Servier; Spouse: Head of BU, Sandoz. C. Lombard Bohas: Consulting or advisory role: Ipsen, Novartis, Pfizer, Advanced Accelerator Applications. T. de Baere: Consulting or advisory role, speaker’s bureau: Guerbet. All other authors have declared no conflicts of interest.