Folfox and intra-arterial DEBIRI as front-line treatment in patients with non resectable colorectal cancer liver metastases (FFCD 1201 phase II trial)

Abstract

Background: 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. Methods: 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%). Results: 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 9mwas 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 27.5m(95% CI, 21.0 - 30.6), median OS was 33.1m(95% CI, 25.7 ; 46.1) and median PFS 10.8m(95% CI, 8.18 ; 12.32). Conclusions: Despite the primary endpoint was not met, front-line DEBIRI + FOLFOX without any targeted agent allow an excellent disease control rate in nonresectable LMCRC with deep responses, leading to secondary resection in 1/3 of pts.