Up until now, some colorectal cancer (CRC) patients and their doctors had no way of determining whether the drug Erbitux (cetuximab) would be a helpful treatment based on the absence of a KRAS gene mutation. On July 6, 2012, the United States Food and Drug Administration (FDA) approved the first genetic test to help doctors decide which colon cancer patients might respond well to cetuximab.
The therascreen KRAS RGQ PCR Kit can tell whether a patient's tumor which has metastasized (spread to other parts of the body) carries a KRAS gene mutation. According to previous studies, if patients have the mutation, then Erbitux is not beneficial.
Colorectal cancer, which can also be called bowel cancer or colon cancer, occurs when there is uncontrolled cell growth in the rectum, colon or appendix. It is the third leading cause of cancer death in the U.S. The American Cancer Society recorded over 141,000 new CRC cases in 2011, and nearly 50,000 deaths in the same year.
Cetuximab targets the EGFR (epidermal growth factor receptor) on the surface of colorectal cancer cells. After some chemicals in the body bind to it, EGFR sets off a complex chain of biochemical reactions inside the cancer cell, which makes it reproduce. Cetuximab works by blocking EGFR, thus stopping the cell from reproducing, resulting in no more colorectal cancer cell growth. This only happens if there is no mutation in the KRAS gene, otherwise the CRC cells continue reproducing, regardless of whether or not the patient has been administered cetuximab.
Alberto Guitierrez, Ph.D., director of the Office of In Vitro Diagnostic Device Evaluation and Safety in the FDA's Center for Devices and Radiological Health, said:
"This test helps clinicians determine whether this specific treatment is an effective option."
For the approval of this genetic test, tumor samples that had been used when Erbitux was being submitted for approval were used. They found that Erbitux only works in patients whose tumors had none of the seven KRAS mutations detected by the test.
The evaluation found that:
- Patients without the KRAS mutation and who received Erbitux had a median survival of 8.6 months
- Those without the KRAS mutation and who did not receive Erbitux had a median survival of 5 months
- Patients with a KRAS mutation and who received Erbitux had a median survival of 4.8 months
- Patients with a KRAS mutation and who did not receive Erbitux had a median survival of 4.6 months
The FDA also approved a new indication for Erbitux to be used alongside FOLFIRI; a chemotherapy medication containing irinotecan, 5-fluorouracil, and leucovorin, as a first line treatment for those with metastatic colorectal cancer with EGFR-expressing, and KRAS wild type (no mutation) tumors.
Survival time was 23.5 months for those receiving Erbitux plus FOLFIRI versus 19.5 months for those on just FOLFIRI among patients with none of the seven KRAS mutations. Median survival times among patients with a KRAS mutation was not significantly different between those on Erbitux and others on just FOLFIRI.
Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said:
"The approval of this new Erbitux indication with the concurrent approval of a genetic test provides clear guidance on selecting patients who will optimally benefit. Clinical trial data leading to the approval of this new indication supports the recommendation to treat those patients whose colorectal tumors do not have KRAS mutations and to avoid treating those with KRAS mutations."
The therascreen KRAS RGQ PCR Kit was developed by QIAGEN Manchester Ltd, England, and Erbitux is co-marketed by Eli Lilly and Company and Bristol-Myers Squibb in the USA.
Peer M. Schatz, Chief Executive Officer of QIAGEN N.V., said:
"We are very pleased to receive FDA approval to launch our therascreen KRAS test in the United States and to play a role in transforming the care of colorectal cancer patients. This approval marks an important step for QIAGEN..."
Written by Sarah Glynn