Metastatic colorectal cancer patients who have variations in codon 12 or 13 did not benefit from the drug.
FDA has made changes to the U.S. prescribing information for Erbitux with regards to treating those with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC). The label states that the drug is not recommended for patients whose tumors have K-ras mutations in codon 12 or 13.
FDA’s revisions included a statement that retrospective subset analyses of metastatic or advanced colorectal cancer trials did not show a treatment benefit for Erbitux in patients whose tumors had these K-ras mutations. These modifications were also made to the clinical studies and clinical pharmacology sections of the product’s prescribing information.
About 40% of patients with mCRC have K-ras mutations, according to ImClone and Bristol-Myers Squibb, the companies that market Erbitux. Signal transduction through the EGFR results in activation of wild-type K-ras protein. In cells with activating K-ras somatic mutations, however, the mutant K-ras protein is continuously active and appears independent of EGFR regulation.
In mCRC Erbitux is approved by the FDA as: a single agent for EGFR-expressing mCRC after failure of both irinotecan- and oxaliplatin-based regimens; a single agent for EGFR-expressing mCRC in patients who are intolerant to irinotecan-based regimens; and in combination with irinotecan for the treatment of EGFR-expressing mCRC in patients who are refractory to irinotecan-based chemotherapy.