FDA Approves Test to Identify Colorectal Cancer Patients Who May Respond to Cetuximab ►NCI Cancer Bulletin for July 24, 2012 - National Cancer Institute

NCI Cancer Bulletin for July 24, 2012 - National Cancer Institute

FDA Approves Test to Identify Colorectal Cancer Patients Who May Respond to Cetuximab

The Food and Drug Administration (FDA) has approved a genetic test to help physicians determine which patients with metastatic colorectal cancer are likely to benefit from the drug cetuximab (Erbitux).
The therascreen KRAS RGQ PCR Kit can detect seven mutations in the KRAS gene in DNA extracted from a patient’s tumor.

Activation of the epidermal growth factor receptor (EGFR), which is often overexpressed on the surface of colorectal cancer cells, promotes cell proliferation. The monoclonal antibody cetuximab binds to EGFR and blocks the receptor’s growth-promoting signaling pathway. Cancer cells that have a mutant KRAS gene, however, can continue to grow even in the presence of cetuximab.

FDA approval of the test was based on a retrospective analysis of biopsy samples from patients participating in the phase III CO.17 clinical trial that supported the original approval of cetuximab. Patients whose tumors lack KRAS mutations (also known as KRAS wild-type tumors) had an overall survival of 8.6 months with the addition of cetuximab compared with 5.0 months with best supportive care alone. For patients whose tumors had KRAS mutations, adding cetuximab did not significantly affect survival.

The FDA has also approved cetuximab in combination with the FOLFIRI regimen as a first-line treatment for patients with KRAS wild-type, EGFR-positive metastatic colorectal cancer. The approval for this new indication was supported by a retrospective analysis of the phase III CRYSTAL trial, which showed a 4-month increase in median survival for patients without KRAS mutations who received cetuximab plus FOLFIRI versus FOLFIRI alone.

Further reading: “Colorectal Cancer Trials Support Gene Testing for Two Drugs”