Although colorectal cancer patients with mutations in the KRAS gene tend not to respond to drugs such as Erbitux® (cetuximab), responsiveness may vary by the specific type of KRAS mutation. These results were published in the Journal of the American Medical Association.
For patients with colorectal cancer, a test of the KRAS gene should be strongly considered before beginning treatment with epidermal growth factor receptor (EGFR) inhibitors such as Vectibix® (panitumumab) and Erbitux® (cetuximab). Vectibix and Erbitux are targeted therapies that inhibit growth of the cancer by binding to a portion of the EGFR, a protein located on the surface of many cancer cells. An estimated 40-50% of colorectal cancers contain a mutation in the KRAS gene. Colorectal cancers that contain a KRAS mutation are unlikely to respond to EGFR inhibitors.
Erbitux is currently approved for the treatment of selected patients with advanced head and neck cancer or advanced colorectal cancer. Researchers recently conducted a study to determine whether patients with certain KRAS gene mutations may still derive benefit from treatment with Erbitux.
In this study researchers evaluated pooled data from 579 metastatic colorectal cancer patients with chemotherapy-refractory disease. In the subset of patients treated with Erbitux (either alone or in combination with chemotherapy), outcomes among patients with a KRAS mutation known as the codon 13 mutation were compared with outcomes among patients with other KRAS mutations.
- Overall survival was 7.6 months among patients with the KRAS codon 13 mutation and 5.7 months among patients with other KRAS mutations.
- Progression-free survival was 4.0 months among patients with the KRAS 13 codon mutation and 1.9 months among patients with other KRAS mutations.
The researchers concluded that Erbitux treatment was associated with a survival benefit in chemotherapy-refractory colorectal cancer patients with the KRAS 13 codon mutation compared with patients with other KRAS mutations. Prospective trials evaluating the role of Erbitux in patients with this specific KRAS mutation may be warranted.
 De Roock W, Jonker DJ, Di Nicolantonio F, et al. Association of KRAS p.G13D mutation with outcome in patients with chemotherapy-refractory metastatic colorectal cancer treated with cetuximab. JAMA. 2010;304:1812-1820.
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