CETUXIMAB ADDITION INCREASES METASTATECTOMY RATE IN OLIGOMETASTATIC COLORECTAL CANCER 

Randomized Controlled Trial of Cetuximab Plus Chemotherapy for Patients With KRAS Wild-Type Unresectable Colorectal Liver-Limited Metastases

Ye LC, Liu TS, Ren L, et al

J Clin Oncol. 2013;31:1931-1938

Study Summary

Various approaches to oligometastatic colon cancer involving the liver include a combination of systemic and local treatments. This study evaluated the benefit of addition of cetuximab to standard treatment in this setting. After resection of their primary tumors, 138 patients with KRAS wild-type synchronous nonresectable liver-limited metastases from colorectal cancer were randomly assigned to receive either chemotherapy (fluorouracil, leucovorin and irinotecan [FOLFIRI] or fluorouracil, leucovorin, and oxaliplatin [FOLFOX]) plus cetuximab (arm A) or FOLFIRI or FOLFOX alone (arm B). The primary endpoint was the percentage of patients who converted to resection for liver metastases. Secondary endpoints included tumor response and survival.

The R0 resection rates for liver metastases were 25.7% (18 of 70 patients) in arm A and 7.4% (5 of 68 patients) in arm B (P < .01). Patients who received cetuximab also had improved response rates (57.1% vs 29.4%; P < .01), increased 3-year overall survival (41% vs 18%; P = .013), and overall survival (median 30.9 vs 21.0 months; P = .013). Median survival in patients who received chemotherapy plus cetuximab and had a resection was 46.4 months.

Viewpoint

This study addresses the important question of whether patients with liver-limited metastatic colorectal cancer who are initially considered unresectable can in fact be successfully downstaged and resected. Many previous studies have demonstrated that the addition of cetuximab to standard chemotherapy certainly increases response rates. It follows, therefore, that an increase in response rate would increase the chance of resectability. The study provides a benchmark for expectations: Approximately one fourth of oligometastatic disease patients randomly assigned to chemotherapy plus cetuximab underwent R0 resections, and these patients subsequently had an impressive median survival of nearly 4 years. An important caveat of this study is the definition of resectability; in fact, most patients had 1-4 lesions and therefore appeared generally favorable to future resection. Whether these results apply to patients with more unfavorable disease requires additional data.