KRAS Data Prompt Cetuximab, Panitumumab Product Label Changes

The US Food and Drug Administration's Office of Oncology Drug Products has announced class labeling changes to product labels for the anti-EGFR (epidermal growth factor receptor) monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix), based on evidence that patients whose metastatic colorectal cancer (mCRC) has KRAS mutations do not benefit from treatment with these agents.

On July 17, 2009, changes were made to the product labels for both drugs, in the sections “Indications and Usage,” “Clinical Pharmacology,” and “Clinical Studies.”

The addition to the Erbitux and Vectibix labels in the “Indications and Usage” section states: “Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for [Erbitux, Vectibix] in patients whose tumors had KRAS mutations in codon 12 or 13. Use of [Erbitux, Vectibix] is not recommended for the treatment of colorectal cancer with these mutations.”

Information added to the Erbitux and Vectibix labels in the “Clinical Pharmacology” section states: “Signal transduction through the EGFR results in activation of wild-type KRAS protein. However, in cells with activating KRAS somatic mutations, the mutant KRAS protein is continuously active and
appears independent of EGFR regulation.”

The “Clinical Studies” section of the Erbitux and Vectibix product labels presents data from retrospective subset analyses of seven randomized clinical trials (five with cetuximab, two with panitumumab) indicating that these anti-EGFR monoclonal antibodies are not effective for treatment of mCRC containing KRAS mutations. KRAS status was assessed in 23% to 92% of the study populations.