A randomized clinical trial of chemotherapy compared to chemotherapy in combination with cetuximab in k-RAS wild-type patients with operable metastases from colorectal cancer: The new EPOC study.

Abstract

3504 Background: Resection of liver metastases from colorectal cancer with or without neoadjuvant chemotherapy is the standard of care. The EPOC study (Nordlinger et al, Lancet 2008) randomised patients between surgery and surgery with chemotherapy and demonstrated an improvement in 3 year progression free survival (PFS) of 7·3% (from 28·1% to 35·4%). As a rational extension to the EPOC study data, the New EPOC study evaluates the benefit of cetuximab, an EGF receptor antibody, in addition to standard chemotherapy in patients with operable liver metastases. Methods: 272 patients were randomised between February 2007 and November 2012 into the New EPOC study. Eligible patients were required to be k-RAS wild type, have operable liver metastases and to be sufficiently fit for chemotherapy and surgery. Patients with the primary tumour in situ, and those who required short course rectal radiation were eligible. Patients were randomised to receive a fluoropyrimidine and oxaliplatin plus or minus cetuximab for 12 weeks before, then 12 weeks following surgery. Patients who had been treated with adjuvant oxaliplatin could receive irinotecan and 5 – fluorouracil. Results: Following a recommendation from the Independent Data Monitoring Committee on 19/11/2012, the New EPOC study was stopped when the study met a protocol pre-defined futility analysis. With 45.3% (96/212) of the expected events observed, progression free survival was significantly worse in the cetuximab arm (14.8 vs 24.2 months, HR (95%CI) 1.50037 (1.000707 to 2.249517) p< 0.048). The result of a pre-planned analysis excluding the 23 patients treated with irinotecan based chemotherapy was similar (15.2 vs 24.2 months, HR 1.565546 (1.014967-2.414793) P<0.043). Conclusions: Although the data are immature, the accumulation of more events is unlikely to change this result. In patients with resectable liver metastases and K-RAS wt tumours the addition of cetuximab to chemotherapy is not beneficial. Clinical trial information: ISRCTN22944367.