Cetuximab Decreases OS in Patients With Resectable Colorectal Liver Metastasis

A long-term analysis of the New EPOC clinical trial led investigators to assert that cetuximab therapy should not be used in patients with resectable colorectal liver metastasis (Lancet Oncol. 2020 Jan 31. Epub ahead of print).

John A. Bridgewater, PhD, University College London Cancer Institute, and co-investigators conducted the long-term follow-up analysis to evaluate the effect of combining cetuximab with chemotherapy onoverall survival (OS) in this patient population.

A total of 272 patients were enrolled in New EPOC and randomized to receive treatment between February 26, 2007, and October 12, 2012. Ultimately, 257 patients were included in the primary analysis and given chemotherapy (n = 128) or chemotherapy plus cetuximab (n = 129).

The progression-free survival (PFS) rate was the primary end point of the study, and secondary end points included OS, pre-operative response, pathologic resection status, and safety.

The median follow-up time was 66.7 months, and the median PFS was 22.2 months in the chemotherapy arm versus 15.5 months in the chemotherapy plus cetuximab arm. The median OS was 81.0 months versus 55.4 months, respectively.

The secondary end points of pre-operative response and pathologic resection were similar between the 2 treatment arms.

According to Dr Bridgewater et al,5 patient deaths may have been treatment-related, including 1 in the chemotherapy arm and 4 in the chemotherapy plus cetuximab arm. 

Decreased neutrophil counts and diarrhea were the most common grade 3-4 adverse events reported in both arms. Patients in the cetuximab plus chemotherapy arm had increased rates of skin rash (16%), thromboembolic events (8%), and oral mucositis (10%) compared with those in the chemotherapy-only arm.

“Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in 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,” Dr Bridgewater and colleagues said.

“Cetuximab should not be used in this setting,” they concluded.—Kaitlyn Manasterski