The role of the KRAS G13D mutation in patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus cetuximab.

Abstract

630 Background: The CRYSTAL and OPUS studies showed that adding cetuximab (cet) to first-line chemotherapy (CT) significantly improved clinical benefit in patients (pts) with KRAS wild-type (wt) mCRC. Pts with KRAS codon 12 or 13 mutations are excluded from cet treatment. Studies suggest that not all KRAS mutations are equivalent in their biologic effects. Occasional responses and prolonged disease stabilization have been recorded following cet treatment of tumors with mainly KRAS codon 13 mutations. We investigated the influence of the most common KRAS codon 13 mutation (G13D) on clinical outcome compared with pts with other KRAS mutations or wt tumors in the CRYSTAL and OPUS trials. Methods: KRAS mutations were detected in tumor DNA from archival material using a PCR clamping and melting curve technique. Treatment arms were compared by KRAS mutation status for progression-free (PFS) and overall survival (OS). Results: In the CRYSTAL study of 1,063 evaluable pts 63% were KRAS wt, 6% were G13D mutant (mt) and 32% had other mutations. In the OPUS study of 315 evaluable pts, 57% were KRAS wt, 7% were G13D mt, and 36% had other mutations. Compared with KRAS wt pts those with G13D mutations did not benefit from the addition of cet to CT (Table). Data of comparisons of the G13D mutation with other KRAS mutations in these studies will be presented. Conclusions: Patients with KRAS G13D mt tumors did not appear to benefit from the addition of cet to first-line CT for mCRC. This analysis confirms the current practice of KRAS mutation testing as the standard diagnostic tool for determining first-line treatment of mCRC pts. [Table: see text] [Table: see text]