This week’s blog post will cover a new development in the world of companion diagnostics. That is, the field in which a diagnostic tool (usually a genetic test) is developed to guide the health care provider’s decision to administer (or not) a specific drug to a patient.

A companion diagnostic is typically developed and clinically tested in conjunction with its companion drug, all in the interest of perpetuating the concept of personalized medicine. Regulatory agencies, such as the United States Food and Drug Administration (FDA), ensure the rigorous testing of the companion diagnostic in order to guarantee that it will reliably predict the patient population who will experience the best outcome on the companion drug. Clinical trials are conducted to guarantee this reliability, thus forming the basis for approval of a drug-diagnostic companion pair.

It is well established that patients with colorectal cancer whose tumors carry a K-RAS mutation will be refractory to treatment with cetuximab. In contrast, if a patient’s tumor does not carry a K-RAS mutation, there is a greater likelihood that cetuximab will be effective.   

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The latest companion diagnostic—The therascreen® KRAS RGQ PCR Kit—was recently FDA-approved in conjunction with the FDA approval of cetuximab as a first-line treatment for colorectal cancer. This is the first K-RAS companion diagnostic approved by the FDA. By testing DNA extracted from resected colorectal tumors, this diagnostic kit is capable of detecting seven somatic mutations in the K-RAS gene and thus will provide assessment of mutation status. This mutation status will guide the health care provider’s decision as to whether to administer cetuximab or not. Using this kit, those patients with colorectal cancer whose tumors are found to be K-RAS mutation positive are not eligible to receive cetuximab, whereas tumors found to be K-RAS mutation negative are eligible to receive cetuximab.

“The K-RAS test has been given premarket approval by the FDA because there are no other tests available to determine whether a patient is K-RAS mutation positive or negative,” says Stephen Little, PhD, Vice President of Personalized Healthcare at QIAGEN, a codeveloper of the kit. “In this case, cetuximab was on the market before the discovery of the relationship between the K-RAS mutation and response to the drug. So we had to retrofit the kit to the drug by going back to perform the phase 3 clinical trial to prove that the diagnostic can predict response to cetuximab.”

According to Little, the impact of the K-RAS mutation kit will be seen in two ways. “First, since this kit became available, cetuximab has moved up from a second-line therapy to a first-line therapy, making it available for a larger population of patients,” says Little. Also, 40% of colorectal tumors contain K-RAS mutations, and thus will not respond to cetuximab. “Second, if 40% of the patients do not respond to the drug, then the health care system is wasting money on that drug. This kit, if used to routinely screen for K-RAS mutations, could save the system over $600M per year. And, in this time of health care cost constraints, I think that is going to be a very important driver.”

Readers, what will be the impact of this kit on the treatment of your colorectal cancer patients?