Background of the study

Colorectal cancer can be divided into several categories, but definitely one of the most crucial in terms of treatment decisions comes from the distinction between tumors that have mutations of RAS genes and those that do not (defined as wild-type). Data from literature clearly show that patients with RAS mutations derive no benefit from the use of a particular class of drugs called “anti-EGFR antibodies”, including cetuximab. Cetuximab is commonly used as first-line treatment in combination with chemotherapy. Even patients who initially achieve benefit from the drug, then experience disease progression, due to mechanisms of acquired resistance. In addition, the first-line treatment with anti-EGFRs seems to select those cell subclones that had or have developed RAS mutations.Retrospective clinical evidence suggests that patients become resistant to anti-EGFR drugs can once again benefit from the treatment with an anti-EGFR after other intervening treatments. However, this evidence is extremely preliminary.

Aim of the study

The study aims at investigating the activity of the “re-challenge” with anti-EGFR as third-line treatment in patients with RAS and BRAF wt tumors who had achieved initial benefit and then progressed during first-line chemotherapy plus anti-EGFR. Another ambitious aim is to identify factors that are able to predict which patients might actually benefit from this therapeutic choice.