KRAS Mutations Predict Metastatic CRC Cetuximab Response Rates

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(ChemotherapyAdvisor) – Cetuximab-based treatments might be more beneficial to patients whose metastatic colorectal cancer (mCRC) tumors contain KRAS p.G13D mutations than those whose tumors contain KRAS codon 12 mutations, according to a systematic review and meta-analysis of objective response rate data pooled from 10 studies.   

The meta-analysis, published in Cancer, included objective response rate data representing a total of 1,487 mCRC patients.

“The results from this systematic review suggest that patients with mCRC who have tumors with the KRAS p.G13D mutation may benefit more from cetuximab treatment than patients who have tumors with KRAS codon 12 mutations,” reported senior author Jin-Ling Tang, MD, PhD, of the School of Public Health and Primary Care at the Chinese University of Hong Kong, and colleagues.   

Among patients who were administered cetuximab-based treatments, those whose tumors contained the KRAS p.G13D mutation had a significantly higher ORR (objective response rate) than patients whose tumors contained KRAS codon 12 mutations (RR 1.64 [95% CI: 1.131-2.384];P=0.009), and significantly lower ORR than those with wild-type KRAS tumors (RR 0.54 [95% CI: 0.381-0.765];P=0.001). In contrast, patients with KRAS p.G13D mutation tumors who were not administered cetuximab had worse ORR than patients with KRAS codon mutation 12 tumors, the authors reported.

Meta-analysis of data on the effects of KRAS p.G13D mutation status on PFS (progression free survival) and OS (overall survival) was not possible because only one study included in the analysis presented hazard ratio statistics, the authors noted. 

“Large, randomized clinical trials will be needed to further confirm these findings and to clarify their clinical implications,” the authors cautioned. They disclosed no funding sources or conflicts of interest.


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