KRAS mutations and the effectiveness of oxaliplatin-based chemotherapy

This study evaluated survival benefit with the use of oxaliplatin (Eloxatin) in relation to KRAS gene status among patients with metastatic colorectal cancer.

Metastatic colorectal cancer (cancer that has spread from the large intestine to distant organs and tissues) is often treated by a combination of chemotherapy and targeted biological agents. The success of metastatic cancer treatment often depends on the molecular behavior of cancer cells. Mutations of the KRAS gene (an important factor in cell growth and survival) are common among colorectal cancer patients and are known to influence the effectivity of agents targeting KRAS controlled cellular activities. Despite vast research regarding the effect of KRAS gene status on the success of certain targeted biological treatments, the effect of KRAS status on the success of oxaliplatin-based chemotherapy regimens has not yet been thoroughly investigated.

This study compared the overall survival of 394 metastatic colorectal cancer patients according to KRAS gene status and previous oxaliplatin treatment. 225 patients were KRAS mutation-negative (referred to as wild-type KRAS status) and 169 patients were found to be KRAS mutation-positive.

Among KRAS mutation-positive patients, overall survival was significantly extended among patients treated with oxaliplatin-based chemotherapy. Among the 131 KRAS-positive metastatic colorectal cancer patients treated with oxaliplatin-based regimens the average overall survival was 28.8 months, compared to 17.8 months among the 38 KRAS-positive patients never treated with oxaliplatin-based chemotherapy. This benefit in survival among KRAS-positive patients remained significant even after accounting for other biological treatments (such as bevacizumab or cetuximab) or chemotherapy agents.

On the other hand, among wild-type KRAS patients, a trend towards improved survival was noted among patients treated with oxaliplatin-based chemotherapy. However, this overall survival benefit was shown as non-significant on further statistical analysis.

This study concluded that oxaliplatin-based chemotherapy shows increased benefit among KRAS mutation-positive metastatic colorectal cancer patients compared to KRAS wild-type cancer patients.

This retrospective analysis only included a small number of patients not treated by oxaliplatin-based chemotherapy. Randomized trials are needed to confirm these results.