The New EPOC study demonstrated a shorter progression-free survival (PFS) with the addition of cetuximab to chemotherapy for operable colorectal liver metastasis. The combination of a liver resection with EGFR inhibition is unique to this study. This analysis explores both surgical quality and the impact of volume of liver resected on outcome.
Data is presented for 263/271 patients (early study withdrawals excluded). Details of surgery were completed by the operating or lead surgeon in 19 UK specialist centres. The report of no residual tumour in the pathological specimen was queried in each case. Volume of liver resected was estimated and patients divided into tertiles (tertile 1: ≤20.5%, tertile 2 20.6-44.1%, tertile 3: 44.2-84.8%) to investigate association with PFS.
Operations were performed on 233/263 patients (118 chemo alone CT, 115 chemo and cetuximab CTX) of which 205 (108 CT, 97 CTX) underwent resection. A further 18 had surgery that included ablation (6 CT, 12 CTX). 155 had major resections (87 CT, 68 CTX) and the median estimated volume of total liver volume resected was the same in both groups (CT 27.8% IQR 17.0-63.4, CTX 27.8% 17.4-63.4). In the CT group PFS was significantly associated with the volume of liver resected (tertile 1 median PFS not reached, tertile 2 28 months, tertile 3 18.7 months, p = 0.02). Those with a smaller resection volume (tertile 1, ≤20%) appeared to have a shorter PFS with cetuximab (median PFS for CT not reached, CTX 15.2 months, HR 2.15 95%CI 1.00-4.57 p = 0.06). By contrast those with a larger volume of liver resected (tertiles 2 & 3) had similar outcomes irrespective of the use of cetuximab (median PFS for CT 20.2 months, CTX 16.9 months, HR 1.06 95%CI 0.65-1.71 p = 0.83). When analysis was restricted to just those with a R0 resection the shorter PFS with cetuximab persisted (HR 1.68 95% CI 1.04-2.71 p = 0.035). Examination of the pathological specimen revealed no residual tumour in 22 patients (14 CT, 8 CTX) of whom 8 have disease progression (6 CT, 2 CTX).
These exploratory analyses suggest the technical aspects of surgery are similar between the treatment groups and that those patients having smaller volume resections may be disadvantaged by the addition of cetuximab.
Clinical trial identification
Legal entity responsible for the study
University Hospital Southampton NHS Foundation Trust
Cancer Research UK
D. O\'Reilly: Received expenses, travel, accommodation or otherwise, from AngioDynamics and Mylan. M. Peterson: Received expenses, travel, accommodation or otherwise, from TeleFlex. N. Heaton: Has provided and been paid, including honoraria, for consulting and/or advisory roles and participating in a speakers\' bureau by Astellas. Has a patent or other royalties/intellectual property under his own account. G. Griffiths: Has provided and been paid for consulting and/or advisory roles for the following companies in the past two years: Sirtex, Celgene, GSK. D. Cunningham: Has conducted research projects on behalf of his institution which have been funded, in whole or in part, by the following companies: Amgen, AstraZeneca, Bayer, Celgene, Merrimack, Medimmune, Merck Serono and Sanofi. T. Maughan: Has provided and been paid for consulting and/or advisory roles for the following company in the past two years: Vertex. J. Garden: Participated in a speakers\' bureau for a Johnson and Johnson (Ethicon) workshop (May 2016). All other authors have declared no conflicts of interest.