Pyrosequencing-based molecular test detects and profiles genetic mutations to predict responses to EGFR inhibitor therapies in colorectal cancer patients.

 

QIAGEN N.V. announced the launch of a new test to determine mutations of the K-ras gene. The K-ras gene is mutated in between 35 percent and 45 percent of metastatic colorectal cancer (CRC) patients. Studies have shown that K-ras testing can better define which CRC patients will benefit from treatment with epidermal growth factor receptor (EGFR) inhibiting monoclonal antibodies, such as Amgen's Vectibix® (panitumumab) and Imclone/Bristol-Myers Squibb's Erbitux® (cetuximab).

QIAGEN's new "PyroMark Q24 K-ras Assay-Kit" is CE-marked for use in second-line treatment of metastatic CRC together with Erbitux or Vectibix and will be available near the beginning of 2009. QIAGEN intends to launch this assay for in vitro diagnostic use in the United States as well.

QIAGEN's new "PyroMark Q24 K-ras Assay-Kit" is able to detect all major and minor known mutations in the K-ras codons 12, 13 and 61, and, in addition, allows the discovery of new mutations as well. This assay is the first molecular assay QIAGEN is launching based on Pyrosequencing, a fundamental technology for short-length, high resolution sequence analysis and quantification. QIAGEN acquired the technology and the associated business in October 2008 from Biotage.

"The design and performance of this assay demonstrates the great potential which Pyrosequencing has for molecular testing in research and molecular diagnostics and underscores the value of this technology as an integral part of our assay and detection portfolio", says Peer Schatz, CEO of QIAGEN. "Unlike other technologies routinely used in molecular diagnostics (such as PCR), Pyrosequencing reads the actual target sequence. While PCR can only detect known sequences, Pyrosequencing can detect all known and unknown genetic variations in all DNA target regions in which mutations occur – and this all at very attractive prices, with built in quality control, in multiplex formats and even from the most challenging starting materials such as fixed tissue."

The market for K-ras testing has seen strong momentum over the last months. A number of recently published studies, including a large multinational prospective study conducted by the Belgian University in Leuven, suggested that the K-ras mutation status is a prognostic biomarker predicting the outcome of EGFR therapies.

In this study, approximately 40% of all CRC-patients had mutated K-ras genes. The trial data indicated that such patients will not benefit from, and in some cases even experience negative reactions to EGFR antibodies, while patients without specific mutations are likely to benefit from this drug treatment.

In response to these studies, European regulators adopted the indication for Vectibix (panitumumab) to include only patients whose tumours carry the unmutated K-ras gene. Earlier this month, the U.S. National Comprehensive Cancer Network (NCCN) issued new guidelines for treatment of CRC which recommended that only patients with tumours characterized by the unmutated K-ras gene shall be treated with EGFR drugs. This organization of 21 cancer centres furthermore recommended that oncologists should generally determine the K-ras gene status of all patients diagnosed with CRC prior to any treatment.