On July 6, 2012 , the U. S. Food and Drug Administration granted approval to cetuximab (Erbitux, ImClone LLC, a wholly owned subsidiary of Eli Lilly and Co) for use in combination with FOLFIRI (irinotecan, 5-fluorouracil, leucovorin) for first-line treatment of patients with K-ras mutation-negative (wild-type), EGFR-expressing metastatic colorectal cancer (mCRC) as determined by FDA-approved tests for this use.
FDA also approved the Therascreen KRAS RGQ PCR Kit (QIAGEN Manchester, Ltd) concurrent with this cetuximab approval.
This approval was based on retrospective analyses in the patient subsets according to K-ras mutation status in tumor samples from patients enrolled in the CRYSTAL trial and in two supportive studies, CA225025 and EMR 62 202-047 (OPUS). The addition of cetuximab to chemotherapy or best supportive care (BSC) resulted in improved survival (OS), progression-free survival (PFS), and overall responses rates (ORR) in the subset with K-ras wild-type tumors; whereas, there was no benefit or potential harm in patients with K-ras mutant tumors. The approval of the companion diagnostic, the QIAGEN Therascreen KRAS RGQ PCR Kit, provides a reliable way to identify these subsets of patients with colon cancer. This QIAGEN test, a genetic assay, is a real-time polymerase chain reaction assay detecting 7 different mutations of the K-ras gene in a tumor specimen. Tumors that are K-ras mutation-negative in this assay are commonly referred to as K-ras wild-type.