Adding Erbitux® (cetuximab) to standard chemotherapy might allow some patients with colorectal cancer and inoperable liver metastases to undergo successful surgical resection of the liver metastasis, according to the results of a study published in the Journal of Clinical Oncology.
Colorectal cancer remains the second leading cause of cancer-related death in the United States. Metastatic colorectal cancer refers to cancer that has spread from the colon to distant sites in the body.
Erbitux is a targeted therapy that inhibits growth of the cancer by binding to a portion of the epidermal growth factor receptor (EGFR), a protein located on the surface of many cancer cells. Erbitux is currently approved for the treatment of selected patients with advanced head and neck cancer or advanced colorectal cancer—namely those with KRAS mutation-negative (also known as KRAS wild-type disease), EGFR-positive, metastatic colorectal cancer.
Researchers conducted a study to evaluate the effects of Erbitux plus chemotherapy as first-line treatment for unresectable colorectal liver metastases (CLMs). The study included 138 patients with confirmed wild-type KRAS colorectal cancer and inoperable metastases confined to the liver. Patients were randomly assigned to receive Erbitux plus chemotherapy or chemotherapy alone. (Chemotherapy consisted of mFOLFOX6 or FOLFIRI.) Treatment continued until the response indicated that the patient was a suitable candidate for surgery, until disease progression, or until unacceptable toxicity.
After a median follow-up of 25 months, the median progression-free survival was 7.3 months, the median survival time was 24.4 months, and the 3-year overall survival rate was 30 percent for all patients. The resection rates for liver metastases were 25.7 percent (18 of 70 patients) in the Erbitux plus chemotherapy group and 7.4 percent (5 of 68 patients) in the chemotherapy alone group. What’s more, the rate of resection with curative intent was significantly higher in the Erbitux group than in the control group.
Patients in the Erbitux group had improved objective response rates (57.1% vs. 29.4%), increased 3- year overall survival rates (41% vs. 18%), and prolonged median survival time (30.9 months vs. 21.0 months) compared with patients who received chemotherapy alone. Patients in the Erbitux group who underwent liver resection had a significantly improved median survival time (46.4 months vs. 25.7 months) compared with those who did not undergo surgery.
The researchers concluded that for patients with initially unresectable KRAS wild-type colorectal liver metastases, Erbitux combined with chemotherapy improved the resectability of liver metastases and improved response rates and survival compared with chemotherapy alone.
The study was conducted only in an Asian population, so the results will need to be validated in a larger study that includes a variety of ethnicities.
Ye LC, Liu TS, Ren L, et al. Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. Journal of Clinical Oncology. Published early online April 8, 2013. doi: 10.1200/JCO.2012.44.8308