Charles Fuchs, MD: Mutations in Colorectal Cancer

For which mutations should patients diagnosed with metastatic CRC be tested?

The practice now of doing mutational assessments in newly diagnosed colorectal cancer is critically important. We have to know about the presence of RAS mutations, because it informs whether or not you're going to use an EGFR antibody. We originally had learned that KRAS, the most common mutation in colorectal cancer, predicted resistance to EGFR antibody therapy. So initially we were just doing the EXON 2 mutations, CODON 12 and 13.

What we learned over the years was that there were other events, other mutations that can occur in KRAS such as CODON 61, 146, among others, and we now now that those mutations can not just occur on EXON 2, but EXONs 3 and 4. Moreover, we know that mutations in those other parts of the KRAS gene similarly predict resistant to EGFR antibodies. So at that point, there was an expansion of assessments to all KRAS mutations.

Subsequent to that, we learned that NRAS also can have the same mutations, and those mutations similarly confer resistance to EGFR antibodies. So the standard of care now needs to be to be to test for all RAS mutations, which actually identifies as many as 50% of patients. So 50% of patients would not be candidates for EGFR antibodies based on that molecular testing. It's critically important that you do all RAS testing on all patients before considering giving an EGFR antibody.

Unresectable Colon Cancer: Case 1

68-year-old man was diagnosed with advanced, unresectable colon cancer has just started treatment with FOLFIRI plus bevacizumab.