Anti-EGFR antibody therapy of colorectal cancer: role of the rare RAS/RAF mutations

In colorectal cancer the most frequently analysed markers are RAS/RAF mutations which have negative predictive role for anti-EGFR antibody therapy. Although the hotspot mutations of the K- and NRAS exon2-4 are well defined the predictive role of rare mutations of other codons is questionable and guidelines are less precise in this respect. We have retrospectively re-analysed the full spectrum of RAS/RAF mutations by NGS in a small cohort of cetuximab treated colorectal cancer patients whoes enrollment was based on KRAS exon2 mutation analysis. We have divided the cohort for RAS/RAF wild type, hotspot- and rare mutant groups and analysed the survival of the them. The Kaplan-Meier analysis indicated that the progression free- and overal survival of the rare mutant group does not differ significantly from the wild type group unlike of those of the hotspot mutants. Till now only one similar retrospective analysis performed before where the survival was not evaluated. However, biochemical analyses of the functional significance of rare RAS mutations suggest that without directly analysing individually their clinical role it cannot be predicted their effect for the efficacy of anti-EGFR antibody therapy.