(ChemotherapyAdvisor) – Patients with metastatic colorectal cancer (mCRC) tumors that harbor any of the most common mutant KRAS codon 12 or 13 alleles are unlikely to benefit from treatment with panitumumab; therefore, this agent should be limited to those with wild-type KRAS, a retrospective analysis of three randomized phase 3 trials reported in the Journal of Clinical Oncology online November 26, has found.

“This study is the largest retrospective analysis evaluating the seven most common mutations in KRAS codons 12 and 13 for prognostic and predictive impact in patients with mCRC receiving an anti-EGFR therapy,” noted Marc Peeters, MD, PhD, of the Department of Oncology, Antwerp University Hospital, Belgium, and colleagues.

In study number 20050203 (first-line treatment), patients were randomly assigned 1:1 to FOLFOX4 (infusional fluorouracil, leucovorin, and oxaliplatin); in study 20050181 (second-line treatment), to FOLFIRI (fluorouracil, leucovorin, and irinotecan); and in study 20020408 (monotherapy), best supportive care, with or without panitumumab 6.0 mg/kg once every 2 weeks.

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“Enrollment was completed in trials 20050203, 20050181, and 20020408 before KRAS was established as a predictive marker for outcomes in patients with mCRC,” the investigators wrote.

In this analysis, 1,053 patients were included from the three studies (n=441; n=486; and n=126, respectively).
“KRAS allele status was ascertained in more than 90% of the patients in each of the three phase III trials,” they noted, with frequency and distribution of mutant KRAS codon 12 and 13 alleles conserved across the trials, equally balanced between treatment and control arms, and consistent with public domain data and prior publications.

Among patients treated on the control arm, no mutant KRAS allele emerged as a consistent prognostic factor for progression-free survival (PFS) or overall survival (OS) or was consistently identified as a predictive factor for PFS or OS in patients receiving treatment with panitumumab.

“Significant interactions for individual mutant KRAS alleles were observed only in study 20050203 with G13D negatively and G12V positively associated with OS in the panitumumab-containing arm,” they concluded. Pooled analysis found only G12A to be associated with a negative predictive OS effect.

These findings are consistent with current clinical treatment guidelines.