598PCETUXIMAB PLUS MFOLFOX-6 AS FIRST-LINE THERAPY FOR PATIENTS WITH KRAS WILD-TYPE UNRESECTABLE COLORECTAL LIVER-LIMITED METASTASES: AN OPEN, NON-RANDOMIZED, MULTICENTER PHASE II CLINICAL TRIAL (CLIME STUDY)

ABSTRACT Aim: This study aims to observe whether the addition of cetuximab(cet) further increases the curative resection rate and improves long-term survival for patients(pts) with KRAS wide-type unresectable colorectal liver limited metastases in China. Methods: Pts were planned to receive cetuximab (500 mg/m2 q2w) plus mFOLFOX-6 including Oxaliplatin 85 mg/m2 plus CF 400 mg/m2 and 5-FU as a 400 mg/m2 bolus followed by 2400 mg/m2 infusion over 46 hours on day 1, repeated every 2 weeks until metastatic leision became resectable or for a maximum of 9 cycles. The primary endpoint was R0 resection rate in intention to treat (ITT) cohort. The second endpoint included objective response rate (ORR), progression-free survival (PFS), over survival (OS) and safety. Per protocol (PP) cohort were defined as pts without major protocol violation and whose tumours were assessed for hepatectomy feasibility by a multidisciplinary team. Results: Between Dec. 2010 and Nov. 2013, 204 pts were screened from 17 centers in China. 130 (63.7%) pts had KRAS exon 2 wild-type tumors. In the ITT cohort (100 cases), the ORR was 61% (95% CI 50.7%, 70.6%), for PP cohort (71 cases), the ORR was 70.4% (95% CI 58.4%, 80.7%). 39 (39%) pts were technically resectable but 34 pts went through surgical treatment. R0 resections were achieved in 27 cases (27%, 95%CI 18.6%, 36.8%), R0/R1 resection and/or radiofrequency ablation were achieved in 33 cases. The ORRs of resectable (39 cases) and unresectable (61 cases) pts were 74.4%, 52.5%, respectively. The median PFS was 10.6m in ITT cohort (95% CI 6.9, 14.7). 90 pts experienced adverse events, mainly including rash (any Gr 68%, Gr 3/4 5%), neutropenia (43%) and malaise (20%). 7 SAEs were reported and 3 pts died. Two pts died during pre-operative chemotherapy from intestinal obstruction and respiratory/cardiac arrest. The other patient died from leukocyte inhibitory and septic shock, and that a causal relationship of study drug cannot be excluded. Conclusions: With interim analyses combination therapy comprising cetuximab and mFOLFOX-6 was well tolerated with acceptable ORR, R0 resection rates and PFS. Disclosure: All authors have declared no conflicts of interest.