Metastatic colorectal cancer: the benefit of combining cetuximab with chemotherapy

The present study investigated if patients with spread colorectal cancer that have mutations in the KRAS gene benefit from Cetuximab treatment.

Cancer that originates in the colon or rectum (parts of the intestine) is called colorectal cancer (CRC). If the cancer has spread from its original location, beyond the intestinal muscle wall and into lymph nodes and other organs, it is called metastatic (spread), or stage IV cancer. If CRC reaches this stage it is not typically curable. These patients are usually treated with chemotherapy, a combination of body-wide, anti-cancer drugs.  With stage IV CRC the main aim of chemotherapy is to maintain the patients' quality of life and increase their life expectancy.

Cancer cells can have proteins called epidermal growth factor receptors (EGFR) on their surface. As the name suggests, these receptors pick up signals that allow cancer cells to grow. Drugs such as Cetuximab (Erbitux) and Panitumumab (Vectibix) are EGFR inhibiting drugs which block the receptors on the tumors, stopping them from getting growth signals. These drugs can be used in combination with chemotherapy.

A gene called KRAS is involved in the normal working of growth factors and receptors. This gene is often damaged or mutated in CRC (in about 40% of all cases). A mutated KRAS has been previously associated with a poor response to EGFR inhibiting drugs.

This paper analyzed data from 1378 patients with metastatic CRC. 533 of these patients had mutations in the KRAS gene. The results of the study showed that patients with a mutation in the KRAS gene called G13D benefited from the combination of both chemotherapy and Cetuximab. In G13D patients, significant increases in progression-free survival (time before cancer resumed its progression) were noticed without a benefit in overall survival. In patients with a different KRAS mutation, called G12V, the treatment combination did not offer a significant benefit. 

In summary, the addition of Cetuximab to chemotherapy seems to provide some benefit to metastatic CRC patients with KRAS G13D–mutant tumors, albeit without extending survival.