EGFR Pathway Test analyzes in sequential reflex fashion more mutations
potentially inhibiting anti-EGFR therapy response in metastatic colorectal
cancer patients
MADISON, N.J., June 1 /PRNewswire-FirstCall/ -- Quest Diagnostics
Incorporated (NYSE: DGX), the world's leading cancer diagnostics company,
today launched the EGFR Pathway test (KRAS with reflex to NRAS, BRAF), the
first laboratory-developed test from a national commercial reference
laboratory for comprehensively identifying, in a single reflex test offering,
genetic mutations in the KRAS, NRAS and BRAF genes. The test is designed to
aid the identification of the roughly half of all metastatic colorectal cancer
(mCRC) patients who, because of certain mutations of the epidermal growth
factor receptor (EGFR) pathway, are believed to be unresponsive to anti-EGFR
cancer therapies for mCRC. While some commercial laboratory tests for
predicting anti-EGFR response analyze certain mutations of the KRAS and BRAF
genes, such as codons 12 and 13 of KRAS, the Quest Diagnostics test detects
mutations in codons 12, 13 and 61 of both the KRAS and NRAS genes and
mutations in exons 11, 12, and 15 of the BRAF gene, in a sequential reflex
manner.
(Note to journalists: For more information on the interplay of genes and
pathways, please refer below to "About Cellular Pathways.")
"Our EGFR Pathway test will provide physicians with the most comprehensive
data available from a single test offering for identifying RAS and BRAF gene
mutations in patients with mCRC who may be considered for anti-EGFR therapy.
Given that research suggests these gene mutations may inhibit therapeutic
response in many patients, our goal is to give physicians a personalized
diagnostic tool that can help them determine more reliably whether or not to
provide therapy with EGFR antagonists to the individual patient," said Dr.
Maher Albitar, M.D., medical director and chief of Research and Development,
Hematology and Oncology, Quest Diagnostics.
Anti-EGFR therapies are designed to impede cellular proliferation caused
by activation of EGFR, but can trigger several side effects, including
fatigue, skin rash, and nausea and vomiting. Up to 40 percent of patients with
mCRC in the U.S. have mutations in the KRAS gene that render anti-EGFR therapy
ineffective. In January 2009, the American Society of Clinical Oncology (ASCO)
produced a provisional clinical opinion (PCO) recommending that all patients
with mCRC who are candidates for anti-EFGR therapy be tested for KRAS gene
mutations (specifically in codons 12 and 13), and that anti-EFGR antibody
therapy should not be administered if mutations are found.
However, fewer than 50 percent of patients with wild-type (normal) KRAS
genes respond to anti-EGFR therapy, suggesting that additional mechanisms may
affect response. Studies demonstrate that in patients with mCRC, about five
percent may have mutations in the NRAS gene and eight percent may have
mutations in the BRAF gene, and that mutations in these genes are associated
with poor anti-EGFR treatment response. In February 2009, The New England
Journal of Medicine published correspondence by Dr. Albitar and his colleagues
at Quest Diagnostics regarding results of a study of 572 colon cancer samples
that found that 11 percent of RAS mutations would have been missed if only
codons 12 and 13 of the KRAS gene had been analyzed (as recommended by ASCO's
PCO), and recommended RAS mutation testing include KRAS and NRAS encompassing
codon 61 in addition to codons 12 and 13.
The Quest Diagnostics EGFR Pathway Test sequentially detects mutations
along the EGFR Pathway, beginning with KRAS followed by NRAS and BRAF. If a
mutation is identified before the entire series is analyzed, the reflex
testing process stops, and the test result is provided to the physician.
Since any individual patient is only likely to experience one mutation in
either KRAS, NRAS and BRAF, combined testing for mutations from these three
genes in the EGFR pathway would theoretically accurately classify more
patients as non-responders than KRAS and/or BRAF testing alone.
"While KRAS mutation analysis of codons 12 and 13 is well established as
an aid in predicting anti-EGFR therapy response, a growing body of research
has revealed that other mutations in the EGFR signaling pathway, including
those at codon 61 of KRAS and NRAS, also impede treatment response in patients
with mCRC," said Jay G. Wohlgemuth, M.D., vice president, Science and
Innovation, Quest Diagnostics. "Our new test will enable physicians to gain a
deeper understanding of a patient's EGFR pathway status, based on the latest
scientific research, than is available using competing tests. We believe this
test is an important diagnostic advance that will help physicians potentially
identify more non-responder EGFR patients who might be missed using standard
KRAS assessments, potentially sparing a substantial number of patients lost
time, not to mention side effects and high costs of anti-EGFR therapies."
In addition to the EGFR Pathway Test, the company launched individual
laboratory tests for identifying mutations in the NRAS and BRAF genes for
physicians who prefer to order individual tests. The company launched its
first laboratory test for detecting mutations in the KRAS gene in August 2008.
Quest Diagnostics is the leader in cancer diagnostics, including tests for
colorectal cancer. In addition to its EGFR Pathway and related laboratory
tests, the company's Enterix business manufactures the InSure(R) fecal
immunochemical test (FIT), an FDA-cleared FOBT test for use in screening for
sources of lower gastrointestinal bleeding, based on laboratory testing of a
stool-based specimen. Quest Diagnostics is also developing a molecular blood
test based on Epigenomics AG's Septin 9 DNA methylation biomarker that can
help physicians detect colorectal cancer based on a patient's blood specimen.
About Cellular Pathways
Within each human cell, genes, lying adjacent to one another, form the
basis for a pathway on which proteins cascade and signal the genes to perform
tasks influencing cellular growth, death and proliferation. In some cancers,
including mCRC, receptors of the epidermal growth factor protein that reside
on each cell are abnormally activated, prompting a cascade effect across a
cellular pathway and the potential for cancerous cellular proliferation.
Anti-EGFR therapies interfere with the cell's epidermal growth factor receptor
to impede cellular proliferation and prompt tumor cell death.
RAS is a family of genes encoding proteins that are involved in
transmitting signals that influence cell growth and survival. Mutations in the
RAS family of cancer-promoting oncogenes, which include KRAS and NRAS, are
implicated in several cancers, including colorectal cancer. BRAF is an
oncogene of RAF, which is a family of proteins typically activated by RAS and
which influence cellular activity.
About Quest Diagnostics
Quest Diagnostics is the world's leading provider of diagnostic testing,
information and services that patients and doctors need to make better
healthcare decisions. The company offers the broadest access to diagnostic
testing services through its network of laboratories and patient service
centers, and provides interpretive consultation through its extensive medical
and scientific staff. Quest Diagnostics is a pioneer in developing innovative
diagnostic tests and advanced healthcare information technology solutions that
help improve patient care. Additional company information is available at
www.questdiagnostics.com.
SOURCE Quest Diagnostics Incorporated
CONTACT: Wendy Bost (Media), +1-973-520-2800, or Laure Park (Investors),
+1-973-520-2900
Web Site: http://www.questdiagnostics.com
(DGX)