580P - Hepatic Arterial Infusion (HAI) of Oxaliplatin Plus Intravenous (IV) Fluorouracil (FU), Leucovorin (LV) and Cetuximab for First-Line Treatment of Unresectable Colorectal Liver Metastases (CRLM): Final Results of a Multicenter Phase 2 Study (CHOICE)

Abstract

ABSTRACT Background To determine the efficacy and tolerance of HAI oxaliplatin plus iv FU/LV and cetuximab in patients (pts) with unresectable CRLM. Methods Main eligibility criteria for this phase 2 study were: histologically proven colorectal adenocarcinoma; tumor wild-type (wt) KRAS status (protocol amendment in 09/2008); unresectable CRLM; no extrahepatic disease (except primary with absent/mild symptoms, and ≤ 3 nonspecific lung nodules ≤ 5 mm in diameter); no prior chemotherapy for metastatic disease; WHO performance status 0-1. After surgical or percutaneous insertion of an implantable HAI catheter, pts were treated with HAI oxaliplatin (100 mg/m2 in 2 hrs) plus iv modified LV5FU2 regimen (LV, 400 mg/m2 in 2 hrs; FU, 400 mg/m2 bolus then 2400 mg/m2 in 46 hrs) every two weeks plus iv cetuximab (400 mg/m2 then 250 mg/m2/week, or 500 mg/m2 every two weeks) until disease progression, limiting toxicity, or CRLM resection. Primary endpoint was objective response rate (ORR) (RECIST 1.0). Secondary endpoints included toxicity (NCI CTC-AE v3.0), disease control rate (DCR), resection rate, progression-free survival (PFS), and overall survival (OS). Results A total of 36 pts were included in 8 centers from 11/2006 to 12/2009. Most of the 35 eligible pts (male, 63%; median age, 54 yrs [range, 33-75]) had extensive disease (≥ 4 CRLM, 88%; bilobar CRLM, 91%). Pts received a median of 10 cycles (range, 1-41). Main severe toxicity was abdominal pain (40%), neutropenia (37%), peripheral neuropathy (34%) and rash (29%). Among 32 evaluable pts, ORR was 87% and DCR was 97%. Among the evaluable pts with wt KRAS (n = 27) or wt KRAS/BRAF (n = 24) tumor status, ORR were 89% and 96% and DCR 96% and 100%, respectively. Overall, 23 of the 35 pts (66%) underwent curative-intent resection and/or radiofrequency ablation (wt KRAS pts, 21 [70%]; wt KRAS/BRAF pts, 20 [74%]). After a median follow-up of 48 months, median PFS was 29 months (median OS, not reached). Conclusions First-line HAI oxaliplatin plus iv LV5FU2 and cetuximab seems feasible and highly effective in pts with unresectable CRLM. Disclosure D. Malka: Membership on an advisory board: Roche Research funding: Amgen, Merck Serono, Sanofi-Aventis. M. Ducreux: Membership on an advisory board: Roche, Pfizer, Sanofi-Aventis, Merck Serono, Amgen Research funding: Roche, Merck Serono, Pfizer. All other authors have declared no conflicts of interest.