First European phase II trial of intravenous (iv) cetuximab (Cet) and hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin in patients with unresectable liver metastases from wt KRAS colorectal cancer (CRC) after systemic therapy failure (OPTILIV, NCT00852228)

3547 Background: HAI of chronomodulated (Chrono) irinotecan (I), 5-Fluorouracil (F) and oxaliplatin (O), or flat O combined with iv F-leucovorin allowed secondary metastases resections and prolonged survival in patients (pts) with CRC liver metastases despite prior chemotherapy failure (Bouchahda, Cancer 2009; Goere, Ann Surg 2010). Purpose: To prospectively evaluate safety and efficacy of combining iv Cet with HAI of IFO in pts with CRC liver metastases. Methods: This Phase II trial involved previously treated pts with unresectable CRC liver metastases. Pts received iv Cet (500 mg/m²) and Chrono or conventional HAI of I (180 mg/m²), F (2800 mg/m²), and O (85 mg/m²) q2 weeks. Liver metastases were resected if adequately downstaged. Results: Planned accrual of 60 pts was reached on 01/24/2012. 3 pts were not treated, 9 are ongoing. 48 consecutive treated pts (18F, 30 M; aged 32-76 years) are fully assessed and monitored. They had PS 0-1 (98%), bilobar liver lesions (69%), a median of 8 metastases (1-50; largest diameter, 57 mm – 15-172). Prior chemotherapy involved one (43%), or two or three (57%) lines. A median of 5 protocol courses (1-13) was given. Main grade 3-4 toxicities per pt were neutropenia (40%), abdominal pain (15%), fatigue (15%), nausea (15%), diarrhea (13%) and sensory neuropathy (4%). Objective response rate was 44% [30-58], with 6% radiological complete responses. Disease control rate was 85%. Secondary liver surgery was performed in 15 pts (31.3%).One pt with 25 metastases (1-6 cm) in all liver segments had pathologic complete response in 24 lesions removed through three-stage hepatectomy. She currently has an off treatment disease-free survival of 17+ months.With a follow up of 4 to 47 months, median progression-free survival is 14.2 months [9.7-18.8], 1- and 2-year survival rates are 92.8% and 59.2% respectively. Conclusions: OPTILIV offers a safe and unusually effective treatment option for patients with CRC liver metastases after failure of systemic chemotherapy within a coordinated medico-surgical strategy.