End of an EPOC.

Top Line: The current NCCN preference for patients with liver-only metastases from colorectal cancer is to go straight to resection.

The Study: But the UK EPOC trial demonstrated an improvement in progression-free survival (PFS) when peri-operative chemo was used. The problem is a lack of clear impact on overall survival (OS). Classic. In New EPOC, all such patients received peri-op chemo randomized to +/- cetuximab. So, it’s old news that the interim analysis of New EPOC showed a surprising decrease in PFS with cetuximab. But if that weren’t enough to dissuade you, long term results show a detriment in OS. Looking back, roughly 250 patients were randomized and about two-thirds had synchronous metastatic disease with most having 1-3 liver mets. Patients in the chemo + cetuximab arm had a median OS of 55 months compared to 81 months for chemo alone. That’s a >2 year difference. Did cetuximab cause direct harm? Well, not in the way you might expect. There were differences in neither disease-related nor treatment-related deaths and no major differences in treatment complications. However, subgroup analysis showed that the survival detriment of cetuximab was mainly in patients with favorable prognostic factors. Diving deeper, cetuximab was associated with more multi-site disease progression and shorter post-progression survival.

TBL: The addition of cetuximab to peri-operative chemo for patients with liver-only mets from colorectal cancer significantly decreases overall survival, potentially due to EGFR-inhibition influencing the biology and subsequent behavior of metastatic disease. | Bridgewater, Lancet Oncol 2020