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.

Gastrointestinal (Colorectal) Cancer
Session Type and Session Title: 
Oral Abstract Session, Gastrointestinal (Colorectal) Cancer
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 3504)
John Neil Primrose, Stephen Falk, Meg Finch-Jones, Juan W. Valle, David Sherlock, Joanne Hornbuckle, James Gardner-Thorpe, David Smith, Charles Imber, Tamas Hickish, Brian Davidson, David Cunningham, Graeme John Poston, Tim Maughan, Myrrdyn Rees, Louise Stanton, Louisa Little, Megan Bowers, Wendy Wood, John A. Bridgewater; Southampton General Hospital, Southampton, United Kingdom; Bristol Haematology and Oncology Centre, Bristol, United Kingdom; University Hospitals Bristol, Bristol, United Kingdom; University of Manchester, Manchester Academic Health Science Centre; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom; Pennine Acute Hospitals NHS Trust, Manchester, United Kingdom; Weston Park Hospital, Sheffield, United Kingdom; Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Clatterbridge Centre for Oncology NHS Foundation Trust, Wirral, United Kingdom; University College London Hospitals NHS Foundation Trust, London, United Kingdom; Royal Bournemouth Hospital, Bournemouth, United Kingdom; University College London, London, United Kingdom; The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom; University Hospital Aintree, Liverpool, United Kingdom; Gray Institute for Radiation Oncology and Biology, University of Oxford, Oxford, United Kingdom; North Hampshire Hospital, Basingstoke, United Kingdom; University of Southampton Clinical Trials Unit, Southampton, United Kingdom; University College London Cancer Institute, London, United Kingdom

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Abstract Disclosures


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.