Combining cetuximab (Erbitux) with standard therapy improved the resectability of previously inoperable liver metastases of colorectal cancer (colorectal liver metastases, or CLMs) and improved response rates and survival compared with chemotherapy alone in patients with normal KRAS CLMs.
A research team led by surgeon Jianmin Xu, MD, PhD, of the Zhongshan Hospital, Fudan University, in Shanghai, China, randomized 138 persons with unresectable CLMs to FOLFIRI (fluorouracil, leucovorin, and irinotecan) or mFOLFOX6 (modified fluorouracil, leucovorin, and oxaliplatin) chemotherapy either with cetuximab (70 patients) or without (68 patients).
Cetuximab targets the epidermal growth factor receptor (EGFR), which is activated in colorectal tumors. All study participants had wild-type (normal) KRAS CLMs; cetuximab is known to be ineffective against tumors with alterations in the KRAS gene, as noted in a statement from the American Society of Clinical Oncology (ASCO). The statement accompanied the release of the study in ASCO’s Journal of Clinical Oncology.
Although surgical removal of CLMs offers the only chance for long-term survival, only 10% to 20% of persons with liver metastases are candidates for such an operation, according to information from ASCO. Current practice guidelines recommend administering “downsizing” chemotherapy or chemotherapy plus targeted therapy as a means of converting initially inoperable CLMs to operable tumors. In this study, liver metastasis resectability was determined based on ability to obtain a complete resection, preserve two contiguous hepatic segments, preserve adequate vascular inflow and outflow as well as biliary drainage, and preserve adequate future liver remnants.
After a median of 25 months of follow-up, the 3-year overall survival rate and median survival time for the entire group of patients were 30% and 24.4 months, respectively. A total of 18 patients receiving cetuximab (25.7%) became eligible for surgery to remove liver metastases, compared with 5 patients in the non-cetuximab group (7.4%). Among those who did undergo liver metastasis resection, median survival time was significantly better for the cetuximab users than for nonusers (46.4 months vs 25.7 months).
Compared with the standard-chemotherapy group, patients who received cetuximab had improved objective response rates (57.1% vs 29.4%), increased 3-year overall survival (41% vs 18%), and prolonged median survival time (30.9 months vs. 21 months).