Axel Grothey, MD, of the Mayo Clinic, Rochester, Minnesota, found the findings presented by Marc Peeters, MD, PhD,¹ at the 2011 European Multidisciplinary Cancer Congress to be of great interest, from both clinical and research perspectives.

“We have two discrepant analyses now for G13D. When we heard the Tejpar data at ASCO,³ we thought, ‘Should these patients be treated? How can we withhold therapy from them?’ There has been a lot of interest in this question,” he told The ASCO Post.

“At Mayo, we now record not just the existence of a KRAS mutation, but the specific codon. This is what we need to do now,” he said.

“Clinically, the data by Dr. Peeters and colleagues now validates the standard of care, but going forward, I agree, we should be looking more at the differential effects of the different KRAS mutations on outcomes. We know from GIST tumors, for instance, that different exons have different therapeutics implications for drug resistance. All KRAS mutations may not be created equal.”

Adding to the discussion, Pierre Laurent-Puig, MD, of the Université Paris Descartes in France, commented on G13D as a prognostic factor. He suggested that “in the first line, there is probably no specific impact of the G13D mutation on prognosis whatever the chemotherapy regimen used, but this should be documented by a meta-analysis. In the second and third lines, there is no argument for a role of G13D mutation in prognosis. In addition to the results presented by Dr. Peeters, the CO-17 [cetuximab] study by de Roock et al² showed no prognostic impact after adjustment for other prognostic markers.”

The G13D allele, however, is found in 8% of advanced colorectal cancer patients, therefore, Dr. Laurent-Puig finds it reasonable to conduct a randomized trial “to explore the possibility to treat G13D-mutated patients for whom we have nothing to propose after the second line of treatment.”

Meanwhile, he agreed with Dr. Grothey: “There should be no change in clinical practice at this time.”

Disclosure: Dr. Grothey reported no potential conflicts of interest.