FDA Approves Revisions to ERBITUX Labeling, Recommends K-ras Testing in Colorectal Cancer Patients

Strategic Insights -

The US Food and Drug Administration (FDA) has approved revisions to the prescribing information for ERBITUX (cetuximab), a medication used to treat certain types of colorectal cancer. The revisions include a modification to the indication statement, which now includes a warning that retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for ERBITUX in patients whose tumors have K-ras mutations in codon 12 or 13. The FDA recommends that all patients with metastatic colorectal cancer be tested for K-ras gene mutations prior to treatment with an anti-EGFR monoclonal antibody therapy.

Key Takeaways:

  • The FDA has approved revisions to the prescribing information for ERBITUX, including a modification to the indication statement that warns against the use of ERBITUX in patients with K-ras mutations in codon 12 or 13.
  • Retrospective subset analyses of metastatic or advanced colorectal cancer trials have not shown a treatment benefit for ERBITUX in patients with K-ras mutations in codon 12 or 13.
  • The FDA recommends that all patients with metastatic colorectal cancer be tested for K-ras gene mutations prior to treatment with an anti-EGFR monoclonal antibody therapy.
  • An estimated 40% of patients with metastatic colorectal cancer have K-ras mutations, while the majority (approximately 60%) have a wild-type K-ras gene.
  • Signal transduction through the EGFR results in activation of wild-type K-ras protein, while mutant K-ras protein is continuously active and appears independent of EGFR regulation.
  • ERBITUX has been approved by the FDA for the treatment of metastatic colorectal cancer as a single agent and in combination with irinotecan or oxaliplatin.

Statistics:

  • 40% of patients with metastatic colorectal cancer have K-ras mutations.
  • 60% of patients with metastatic colorectal cancer have a wild-type K-ras gene.
  • 90% of severe infusion reactions associated with ERBITUX occurred during the first infusion, despite premedication with antihistamines.
  • 55% (199/365) of patients receiving ERBITUX had hypomagnesemia, with 6-17% experiencing severe (NCI CTC grades 3 & 4) cases.
  • 88% of 1373 patients receiving ERBITUX in clinical trials developed acneform rash.

Sources:

  • FDA news release, "FDA Approves Revisions to ERBITUX Labeling, Recommends K-ras Testing in Colorectal Cancer Patients"
  • ImClone Systems press release, "ImClone Systems, Bristol-Myers Squibb and Lilly Recommend K-ras Testing in Colorectal Cancer Patients"
  • ERBITUX Prescribing Information, "BOXED WARNINGS, INFUSION REACTIONS, PULMONARY TOXICITY, DERMATOLOGIC TOXICITIES, ELECTROLYTE DEPLETION, PREGNANCY, ADVERSE EVENTS"
  • Bristol-Myers Squibb website, "About ERBITUX"
  • Lilly website, "About ImClone Systems"
  • Bristol-Myers Squibb website, "About Bristol-Myers Squibb"