KRAS Mutation Predicts Treatment Outcomes of Anti-EGFR Therapies

April 2011, Vol 2, No 2 - In the Literature

Mutation in the KRAS gene has been shown to prevent the benefit of antiepithelial growth factor receptor (EGFR) therapy in patients with colorectal cancer (CRC) in previous studies. Ongoing randomized clinical studies are now investigating whether KRAS testing can help predict survival outcomes in patients with advanced CRC who are receiving cetuximab (Erbitux) or panitumumab (Vectibix) therapy.

In a new meta-analysis (Dahabreh IJ, et al. Ann Intern Med. 2011;154:37-49), 45 publications were eligible for analysis, representing 24 nonoverlapping studies. Of these, 4 were reanalyses of randomized controlled trials of anti- EGFR therapy compared with best supportive care or with chemo therapy alone, from which no significant benefit was found in overall survival (OS) or progression-free survival (PFS) in patients with KRAS mutations.

The 22 studies with nonoverlapping populations showed a specificity of 0.49 (positive likelihood ratio, 7.35) and a sensitivity of 0.93 (negative likelihood ratio, 0.55).

This meta-analysis of patients with CRC with or without the KRAS mutation who were treated with anti-EGFR therapy shows that OS is almost 80% longer in those with wild-type KRAS. Furthermore, median PFS or time to progression was shorter in patients with KRAS-positive tumors than with the wild-type KRAS.

This high positivity ratio suggests that KRAS mutations are a strong predictor of reduced survival, disease progression, and treatment failure. This study corroborates the warning on the US Food and Drug Administration (FDA) labeling that restricts the use of anti-EGFR antibody therapy to patients with CRC who test negative for KRAS mutations