RAS mutation status influence on the treatment effect of panitumumab has been evaluated in a recent prospective-retrospective multicenter analysis (Peeters, M et al.). This retrospective-prospective analysis of a phase 3 randomized trial examined the influence of extended RAS mutation evaluation on second-line efficacy of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab or FOLFIRI alone in 1186 patients with metastatic colorectal cancer (mCRC). RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4, NRAS exons 2, 3, 4, BRAF exon 15) were detected in 18% of KRAS exon 2 wild-type tumors. Panitumumab improved progression-free and overall survival in wild-type KRAS exon 2 tumors, with further improvement in those with extended RAS wild-type status.
Patients with RAS mutations were unlikely to benefit from panitumumab+FOLFIRI and the benefit-risk of panitumumab+FOLFIRI was improved in the wild-type RAS population compared to the wild-type KRAS exon 2 population. Extended RAS testing should be recommended in all cases of mCRC.
