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) (CHOICE): A multicenter phase II study.

Abstract

3558 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 II study (2-step Simon design) were: histologically proven colorectal adenocarcinoma; tumor wild-type 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 2,400 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 resection. Primary endpoint was objective response rate (ORR) (RECIST). Secondary endpoints included toxicity (NCI CTC-AE v3.0), disease control rate (DCR), resectability rate, progression-free survival (PFS), and overall survival (OS). Results: A total of 36 pts were included in 6 centers from 11/2006 to 12/2009. Planned interim analysis on the 23 first pts (male, 61%; median age, 53 yrs [range, 33-75]) showed that most had extensive disease (≥ 4 CRLM, 86%; bilobar CRLM, 91%). Pts received a median of 10 cycles (range, 2-23). Main severe toxicity was peripheral neuropathy (61%), abdominal pain (52%), neutropenia (43%), and rash (30%). Among 21 evaluable pts, ORR was 90% (95%CI, 70-99; intent-to-treat ORR among the 23 pts, 83% [95%CI, 61- 95]) and DCR was 100% (95%CI, 84-100). Among the 23 pts, 11 (48%) underwent R0 resection and/or radiofrequency ablation. After a median follow-up of 11 months, median PFS was 20 months (median OS, not reached; 12- and 18-month OS, 100%). Conclusions: First-line HAI oxaliplatin plus iv LV5FU2 and cetuximab seems feasible and highly effective in pts with unresectable CRLM. Analysis on the whole pt population will be presented at the meeting. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline Amgen, Merck Serono, Novartis, Pfizer, Roche, sanofi-aventis Amgen, Merck Serono, Novartis, Pfizer, Roche, sanofi-aventis Merck Serono, Pfizer, Roche, sanofi-aventis Amgen, Roche