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.