This article is more than 5 years old. Information may no longer be current.
Four biomarkers predicted 70% of EGFR-targeted therapy nonresponders
Click Here to Manage Email Alerts
AACR 100th Annual Meeting
A comprehensive examination of the EGFR signaling pathways, including the role of KRAS, BRAF, PIK3CA and PTEN, should be conducted before selecting patients for treatment with EGFR-targeted therapies such as cetuximab and panitumumab, according to the results of a study presented at the AACR 100th Annual Meeting.
Although it is widely accepted that KRAS mutations play a role in
resistance to EGFR therapies, these mutations only account for about 40% to 50%
of nonresponders, according to Frederica DiNicolantonio, PharmD, PhD,
research fellow, laboratory of molecular genetics at The Institute for
Cancer Research and Treatment,
University of Turin Medical School. 
Listen
to hear Dr. DiNicolantonio comment on the clinical application of these
results.
Di Nicolantonio and colleagues conducted univariate and multivariate analysis of KRAS and BRAF mutations, which cannot occur at the same time, in addition to deregulation of the PIK3CA/PTEN pathway. They retrospectively reviewed gene mutations in tumor samples of 132 patients with metastatic colorectal cancer. Patients were treated with EGFR-targeted monoclonal antibody regimens.
Forty-one of 42 patients with KRAS wild-type tumors, but carrying alterations in any of the remaining biomarkers did not respond to treatment with an EGFR-targeted monoclonal antibody. Seventy-four out of 77 patients with alterations in any of the four biomarkers did not respond to treatment with an EGFR targeted monoclonal antibody; compared to 23/55 'quadruple negative' cases who responded. Mutations in KRAS, BRAF or PIK3CA were associated with a lack of response to EGFR-targeted monoclonal antibody regimens (P<.001) and had a negative impact on survival.
Patients with two alterations (n=24) did far worse compared with other patients; four patients had stable disease, but the remaining 20 progressed.
“If you look at patients that did respond, the vast majority of them did not have alterations in any of these four markers, with the exception of a few outliers,” Di Nicolantonio said. “On the other side, if you look at nonresponders you can see that the majority of them had one molecular marker altered and a significant, about a quarter, had two altered genes.
“If you take the four biomarkers together, we can identify about 70% of patients not responding to EGFR-targeted therapies and we believe this will be a major improvement compared to current practice,” she said. – by Leah Lawrence
For more information: