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Moderator John L. Marshall, MD, introduces a panel discussion focused on the treatments available in the second- and later-line setting for patients with metastatic colorectal cancer (CRC) with a conversation on the expanded definition for KRAS mutations. The conversation includes expert perspectives from Johanna Bendell, MD, Marwan Fakih, MD, Heinz-Josef Lenz, MD, and Alan P. Venook, MD.
Until recently, KRAS mutation testing included only exon 2 at codons 12 and 13, notes Fakih. However, a better understanding of the pathway and improvements in detection tools now demonstrates that mutations in KRAS exon 3 and 4, including NRAS exon 2 and 3, are predictive of response to EGFR inhibitors in CRC, notes Lenz. In general, this expanded criteria results in 20% more patients being ineligible for treatment with EGFR inhibitors, such as cetuximab and panitumumab.
The collection of mutational analyses from several trials has provided ample evidence to begin expanded RAS testing, Bendell believes. Moreover, as a result of this new evidence, if a patient has recently started treatment with an EGFR inhibitor based on traditional KRAS criteria it may be beneficial to retest using the expanded criteria, the panelists believe.