Chemoembolization with Drug-eluting beads loaded with Irinotecan (DEBIRI) increased overall survival in a small randomized phase III study, as compared with intra-venous chemotherapy, in heavily pretreated patients (pts) with liver-dominant metastases from colorectal cancer (LMCRC). First line DEBIRI in combination with systemic chemotherapy may show interesting results in terms of survival, local control and secondary resection rate.
FFCD 1201 is a single-arm, open-labelled phase II study. Pts with LMCRC received mFOLFOX6 with hepatic intra-arterial DEBIRI. In case of bilobar disease, 4 courses of DEBIRI were performed with 100mg of irinotecan, every 2 weeks, alternating right and left lobe, or 2 sessions with 200mg with both lobes treated during the same session. Eligibility criteria included no prior CT for metastatic disease, non-resectable liver-dominant disease, liver involvement < 60%, adequate organ function, age ≥ 18 years, PS ≤ 2. The primary endpoint was progression-free survival (PFS) rate at 9 months (m) (Fleming design, H0: 55%, H1: 75%).
57 pts were enrolled with a median age of 63 years (44 to 78); PS 0-1 95%; median number of LM 9.5 (1 to 20). 49% of pts received the full planned intra-arterial cycles and 87.5% at least 50% of the planned treatment. Main grade 3-4 toxicities were neutropenia (24.6%), diarrhea (12.3%), abdominal pain (10.5%), and pancreatitis/cholecystitis (8.8%/5.3%). One toxic death occurred. PFS rate at 9 m was 53.6% (95% CI, 41.8% - 65.1%). Disease control rate (RECIST) was 92.8% (complete response 3.6%, partial response 69.6%, stable disease 19.6%). Tumor shrinkage > 20% occurred in 85.7% of pts, with a median depth of response of -47% (-100% to + 38%). After FOLFOX + DEBIRI, 19 pts (33%) had a R0 surgery +/- ablative therapy. With a median follow-up of 27.5 m (95% CI, 21.0 - 30.6), median OS was 33.1 m (95% CI, 25.7 ; 46.1) and median PFS 10.8 m (95% CI, 8.18 ; 12.32).
Despite the primary endpoint was not met, front-line DEBIRI + FOLFOX without any targeted agent allow an excellent disease control rate in non-resectable LMCRC with deep responses, leading to secondary resection in 1/3 of pts.
Clinical trial identification
Legal entity responsible for the study
Fédération Francophone de Cancérologie Digestive.
S. Pernot: Honoraria: Amgen; Consulting or advisory, travel, accommodations, expenses: Amgen, Merck. P. Artru: Honoraria: Roche, Amgen, Bayer, Servier, Lilly, Merck; Consulting or advisory role: Roche, Merck; Speaker's bureau: Roche, Merck, Servier; Travel, accommodations, expenses: Roche, Merck, Bayer. D. Tougeron: Consulting, advisory role: Amgen, Sanofi, Merck Serono, Bristol-Myers Squibb, MSD; Travel, accommodations, expenses: Sanofi, Amgen; Honoraria: Amgen, Roche, Novartis, Sanofi, Bristol-Myers Squibb, Merck Serono, MSD. C. De La Fouchardière: Consulting, Advisory role: Lilly, Roche, Bayer, Shire, Amgen; Travel, accommodations, expenses: Roche, Celgene, Amgen; Research funding: Roche. J-L. Raoul: Consulting or advisory role: Bayer Schering Pharma, Taiho Pharmaceutical, BTG; Research funding: Celgene Honoraria: Bayer, Taiho Pharmaceutical, Merck Serono. L. Dahan: Honoraria: Sanofi, Amgen. R. Guimbaud: Travel, accommodations, expenses: Merck Serono, Roche. P. Michel: Travel, accommodations, expenses: Lilly, Merck, Bayer, Hospira. O. Pellerin: Consulting or advisory role: Terumo; Travel, accommodations, expenses: Gore; Research Funding: B. Braun. J. Taieb: Consulting or advisory role: Roche, Merck KGaA, Amgen, Celgene, Lilly, Baxalta, Servier, Sirtex Medical; Speaker's bureau: Servier, Amgen, Baxalta, Roche/Genentech, Sanofi, Merck, Lilly. All other authors have declared no conflicts of interest.