As reported in The Lancet Oncology by Bridgewater et al, the phase III New EPOC trial has shown that the addition of perioperative cetuximab to chemotherapy was associated with significantly poorer overall survival in patients with KRAS wild-type resectable colorectal cancer liver metastases.
An interim analysis from the trial had shown poorer progression-free survival with the addition of cetuximab. The current longer-term analysis was focused on overall survival outcomes.
“Although the addition of cetuximab to chemotherapy improves the overall survival in some studies [of] patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting.”— Bridgewater et al
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In the open-label multicenter trial, 257 patients were randomly assigned between February 2007 and October 2012 to receive chemotherapy (consisting of oxaliplatin, l-folinic acid or d,l-folinic acid, and fluorouracil; or oxaliplatin plus capecitabine) with (n = 129) or without (n = 128) cetuximab before and after liver resection. The current analysis was performed 5 years after the last patient was recruited, as defined in the protocol. Trial recruitment was halted prematurely on Trial Steering Committee recommendation in November 2012.
Median follow-up was 66.7 months.
Median progression-free survival was 22.2 months (95% confidence interval [CI] = 18.3–26.8 months) in the chemotherapy group vs 15.5 months (95% CI = 13.8–19.0 months) in the chemotherapy plus cetuximab group (hazard ratio [HR] = 1.17, 95% CI = 0.87–1.56, P = .304). In the previously reported interim analysis, median progression-free survival after median follow-up of 21 months was 20.5 months vs 14.1 months (HR = 1.48, P = .030).
Median overall survival was 81.0 months (95% CI = 59.6 months–not reached) in the chemotherapy group vs 55.4 months (95% CI = 43.5–71.5 months) in the chemotherapy plus cetuximab group (HR = 1.45, 95% CI = 1.02–2.05, P = .036).
No significant differences between groups were observed in terms of preoperative response or pathologic resection status.
Four deaths in the chemotherapy plus cetuximab group and one in the chemotherapy group were considered possibly related to treatment.
The investigators concluded, “Although the addition of cetuximab to chemotherapy improves the overall survival in some studies [of] patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting.”
John Bridgewater, PhD, of UCL Cancer Institute, University College London, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Cancer Research UK. For full disclosures of the study authors, visit thelancet.com.