Randomized phase 2 trial of hepatic arterial infusion of oxaliplatin after surgery of four or more colorectal liver metastases

A multicenter randomized phase 2 trial in France evaluated hepatic arterial infusion (HAI) versus intravenous (IV) adminstration of oxaliplatin, added to adjuvant IV fluorouracil-leucovorin (LV5FU2) after curative-intent surgery of ≥ 4 colorectal liver metastases (CRLM). The trial included 99 patients with ECOG performance status 0 or 1, who underwent resection or ablation after preoperative IV chemotherapy. Patients were randomized 1:1 to receive adjuvant oxaliplatin via HAI (HAI group, n=50) or IV infusion (IV group; n=49), both combined with IV LV5FU2 for at least 3 months. The primary endpoint was hepatic recurrence-free survival (h-RFS). After a median follow-up of 59 months (IQR 45-71), the median h-RFS was 25 months in the HAI group versus 12 months in the IV group (HR 0.63; p=0.047); the median RFS was 14 months versus 9 months (HR 0.63; p=0.03); and the median overall survival was 74 months versus 57 months (HR 0.61; p=0.11). The five-year OS rate was 62% in the HAI group and 47% in the IV group. Grade 3 or 4 adverse events occurred in 58% of the HAI patients and 32% of the IV patients; no treatment-related deaths were reported. The authors conclude that adjuvant HAI oxaliplatin plus LV5FU2 improved h-RFS after curative-intent surgery of CRLM, with an acceptable safety profile.