Influence of KRAS p.G13D Mutation in Patients With Metastatic Colorectal Cancer Treated With Cetuximab

Mechanisms of resistance to anti-EGFR therapy in colorectal cancer

“…Moreover, a further analysis that investigated the updated pooled data sets from the CRYSTAL and OPUS studies designed by Tejpar et al also shows a similar result [39]. In contrast, a more recent retrospective analysis of 110 patients treated with cetuximab, indicates that patients with KRAS G13D mutations were unlikely to respond to cetuximab [40]. There was no significant difference between patients carrying KRAS G13D mutations and patients with other KRAS mutations in terms of OS and PFS (OS: 8.2 VS 14.6mon, HR = 0.50, P = 0.084; PFS: 4.96 VS 3.1mon, HR = 0.88, P = 0.72).…”

Mutant KRAS Codon 12 and 13 Alleles in Patients With Metastatic Colorectal Cancer: Assessment As Prognostic and Predictive Biomarkers of Response to Panitumumab

“…However, this improved survival in patients with KRAS G13D was not significant in the cetuximab monotherapy arm, and therefore the confounding effect of the chemotherapy backbone cannot be excluded. 12 In addition, a recent retrospective analysis of 110 patients treated with cetuximab 31 reported that patients whose tumor harbored a KRAS G13D allele did not benefit from cetuximab treatment (n ϭ 12) and had a trend toward lower OS compared with patients whose tumors harbored either wt KRAS or one of the other KRAS mutations. Although pani-tumumab and cetuximab recognize similar epitopes, 32 they are of different antibody isotypes and may have different abilities to bind to EGFR mutations.…”

“…The cetuximab studies 12,13,31 and the analysis reported here were limited by their retrospective nature, they used subset analysis, and were subject to chance observations. None of the studies made adjustments for multiple testing.…”

Colorectal cancer in Chinese patients: current and emerging treatment options

“… 36 On the contrary, the mutation G13D in exon 2 has been associated with better response to EGFR antibodies than other KRAS mutations, but the data are mixed. 37 , 38 In addition to the exon 2 KRAS mutation, other mutations such as KRAS mutation exons 3–4 and NRAS mutation exons 2–4 have also emerged to be clinically relevant biomarkers of a lack of response to EGFR antibodies. For example, treating RAS -mutant tumor patients with panitumumab may even have a detrimental effect on survival as shown in the Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic CRC to Determine Efficacy (PRIME) study, where patients were randomized to first-line chemotherapy with or without panitumumab.…”