568P - Safety and Efficacy of Intravenous Cetuximab (CET) and Hepatic Artery Infusion of Irinotecan, 5-Fluorouracil and Oxaliplatin in Patients with Unresectable Liver Metastases from Wt Kras Colorectal Cancer (CRC): Results from Optiliv European Phase II Trial

Abstract

ABSTRACT Background Hepatic artery infusion (HAI) of chronomodulated (Chrono) irinotecan (I), 5-Fluorouracil (F) and oxaliplatin (O), or flat O combined with intravenous (iv) F-Leucovorin allowed secondary metastases resections and prolonged survival in patients (pts) with CRC liver metastases despite prior failure of iv chemotherapy (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 pretreated pts with unresectable CRC liver metastases receiving iv Cet (500 mg/m2) and Chrono or Conventional (Conv) HAI of I (180 mg/m2), F (2800 mg/m2), and O (85 mg/m2) q2 weeks. Liver metastases were resected whenever adequately downstaged. Results Accrual of 64 pts (42 M, 22F; age, 33-76 years; 4 ongoing) was complete at 9 centers (4 countries) on 13/03/2012. In 62 monitored pts: PS 0/1/2 (61/36/3%), bilobar liver lesions (84%), a median of 9 metastases (1-50; largest diameter, 54 mm; range, 15-172) involving a median of 6 segments (1-8). Pts received one (44%), two (30%) or three (26%) prior iv chemotherapy lines. A median of 5 courses (1-13) was given to 59 pts (Chrono, 18; Conv, 41; 3 never treated), with artery occlusion as main cause of withdrawal (53%). Main grade 3-4 toxicities per pt were neutropenia (39%), abdominal pain (25%), fatigue (17%), diarrhea (15%), and nausea (10%). Grade 3 sensory neuropathy occurred in 3% of the pts. Intent-to-treat objective tumor response rate was 45% [95% CL,31-59], including 2 radiological complete responses. Disease control rate was 83%. Per-protocol secondary liver surgery rate was 33.3% [20.4-46.2]. One pt had pathologic complete response in 24/25 metastases in all liver segments (1-6 cm) and has been disease-free for 25+ months and alive at 38+ months. Median progression-free survival (41 events) was 9.1 months [6.5-11.6]. Preliminary median survival (19 events) is 28.6 months [16.3-40.9]. Conclusions The combination of intravenous cetuximab with triplet HAI chemotherapy offers a safe and highly effective treatment option for patients with chemotherapy- refractory CRC liver metastases. Support: ARTBC International, Villejuif; Merck-Serono & Pfizer (France). Disclosure All authors have declared no conflicts of interest.