Study will identify lung cancer patients
for upfront Iressa treatment
Using marker of sensitivity, researchers
seek to determine response to targeted therapy drug
BOSTON - November 15, 2004 - Earlier this year researchers
at two Boston hospitals announced their discovery of a genetic marker
that could predict which lung cancers would respond to treatment
with the targeted-therapy drug Iressa (gefitinib). Now members of
the same teams have launched a study using this marker to identify
at the outset patients most likely to respond to the drug. Led by
physicians from the Massachusetts
General Hospital (MGH) Cancer Center, the clinical trial is
the first to use Iressa as an initial treatment for advanced non-small-cell
lung cancer (NSCLC), the most common and deadly form of the disease.
MGH study looked back at a few selected patients in an effort
to correlate their response to Iressa with mutations in the drug's
protein target," says Lecia Sequist, MD, of the MGH Cancer
Center, who will lead the clinical trial under the direction of
Thomas Lynch, MD, director of the MGH Thoracic Oncology Center.
"Now we will prospectively try to determine the response rate
to Iressa in patients known to have these mutations, further testing
the principles discovered in the earlier investigations."
In April research teams from the MGH and from Dana-Farber Cancer
Institute simultaneously announced discovering that specific mutations
in the epidermal growth factor (EGFR) protein identified a subset
of NSCLC that was sensitive to treatment with Iressa. One of several
new drugs that target the molecular activity underlying cancer development,
Iressa disrupts EGFR function, halting a sequence of signals that
can lead to malignant tumor growth. Despite the fact that early
clinical trials found a significant response in only a few patients,
Iressa was approved by the FDA in 2003 because there were no other
treatment options for NSCLC patients for whom standard chemotherapy
The earlier MGH study, published in the New England Journal of
Medicine, also found that the identified EGFR mutations accelerated
the protein's activity, both stimulating the growth of tumor cells
and making the receptors 10 times more sensitive to Iressa's action.
In the months following the marker's discovery, a test to screen
for the sensitizing mutations was developed by the Laboratory of
Molecular Medicine at the Harvard-Partners
Center for Genetics and Genomics (HPCGG). The test is currently
available to cancer specialists through the HPCGG and will soon
be licensed to a commercial diagnostic laboratory for broader availability.
Conducted by a collaborative group organized through the MGH, the
new study will enroll patients recently diagnosed with advanced
NSCLC who have not yet received any treatment. Potential participants
will be tested for EGFR mutations, and those found to have the sensitizing
mutations will receive Iressa as a first-line treatment, instead
of after the failure of other therapies as is current practice.
Patients without the sensitizing mutations may be referred to other,
more appropriate clinical trials.
The researchers anticipate screening 150 NSCLC patients in order
to identify 30 mutation-positive participants. The trial, which
is anticipated to run for one to two years, is being sponsored by
AstraZeneca, the manufacturer of Iressa. Additional information
is available by calling the MGH Cancer Center at (877) 726-5130
and asking for information about the TARGET trial.
"We all know that cancer is different in different people and
that no one treatment will work for everyone," says Lynch,
who is principal investigator of the new study. "As one of
the first attempts to 'personalize' cancer therapy, this trial will
be a great step forward in matching treatments with the patients
most likely to benefit from them."
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School (HMS). The
MGH conducts the largest hospital-based research program in the
United States, with an annual research budget of more than $400
million and major research centers in AIDS, cardiovascular research,
cancer, cutaneous biology, medical imaging, neurodegenerative disorders,
transplantation biology and photomedicine. In 1994, MGH and Brigham
and Women's Hospital joined to form Partners HealthCare System,
an integrated health care delivery system comprising the two academic
medical centers, specialty and community hospitals, a network of
physician groups, and nonacute and home health services.
In 2001, HMS and Partners created the Center for Genetics and Genomics
with the mission to promote genetics and genomics in research and
clinical medicine at Partners and HMS-affiliated institutions.
Media Contacts: Sue
McGreevey, MGH Public Affairs
Harvard-Partners Center for Genetics and Genomics
Physician Referral Service: 1-800-388-4644
Information about Clinical Trials