Among patients with previously untreated, metastatic colorectal cancer, the addition of Erbitux® (cetuximab) to Avastin® (bevacizumab) and chemotherapy resulted in shorter progression-free survival and worse quality of life. These results were published in the New England Journal of Medicine.
Colorectal cancer remains the second leading cause of cancer deaths in the United States. Metastatic colorectal cancer refers to cancer that has spread from the colon to distant sites in the body. Standard treatment for metastatic colorectal cancer typically involves combination chemotherapy, and may also include treatment with a targeted therapy such as Avastin.
Avastin is a targeted anticancer drug that slows or prevents the growth of new blood vessels by inhibiting a protein known as VEGF; this deprives the cancer of oxygen and nutrients. Through its effects on blood vessels, Avastin may also improve the delivery of chemotherapy to cancer. Avastin has been shown to improve treatment outcomes in selected patients with advanced colorectal, breast, and non–small cell lung cancer, and is also being evaluated in other types of cancer.
Erbitux is a targeted anticancer drug that works by binding to a protein receptor called the epidermal growth factor receptor (EGFR). EGFR is involved in cellular growth and replication, and by targeting EGFR, the growth of cancer can be reduced or delayed. Erbitux has been shown to improve outcomes in selected patients with colorectal cancer or head and neck cancer. Studies suggest that the effectiveness of Erbitux is influenced by mutations in a gene known as KRAS. Patients whose tumors contain mutations in the KRAS gene may derive little benefit from Erbitux.
Because Avastin and Erbitux exert their effects through different pathways (both of which appear to be important in colorectal cancer), researchers hypothesized that the combination of the two drugs may be more effective than either alone. To evaluate the combination of Avastin and Erbitux, researchers in the Netherlands conducted clinical trial among 755 patients with previously untreated, metastatic colorectal cancer.
Patients were assigned to one of two treatment groups:
- Chemotherapy plus Avastin
- Chemotherapy plus Avastin plus Erbitux
Chemotherapy consisted of a combination of Xeloda® (capecitabine) and Eloxatin® (oxaliplatin).
Unexpectedly, the results indicated that the combination of Avastin and Erbitux resulted in worse progression-free survival and worse quality of life. Progression-free survival was 10.7 months among patients treated with chemotherapy plus Avastin, and 9.4 months among patients treated with chemotherapy plus Avastin plus Erbitux.
The researchers also analyzed the effects of KRAS mutations. They found that among patients without KRAS mutations, survival was similar in the two treatment groups. Among patients with KRAS mutations, however, treatment with the combination of Avastin and Erbitux significantly worsened both progression-free and overall survival.
The researchers concluded that the addition of Erbitux to Avastin and chemotherapy resulted in worse progression-free survival and worse quality of life among patients with metastatic colorectal cancer. Outcomes were particularly poor for patients who had a KRAS mutation.
Reference: Tol J, Koopman M, Cats M et al. Chemotherapy, bevacizumab, and cetuximab in metastatic colorectal cancer. New England Journal of Medicine. 2009;360:563-72.