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 Oncologists hope that by understanding the genetic underpinnings of
cancer rather than focusing on whether it originated in the breast
or the liver, they will be able to give patients better, more
personalized and more effective treatments.
But leading cancer experts say that as doctors have tested that
theory more closely, they are seeing both successes and failures,
suggesting that the ideal route to treating cancer may be far more
complicated than hoped.
At the moment, there is not enough understanding of the mutations
that drive cancer growth, said Dr. Richard Pazdur, chief of oncology
at the U.S. Food and Drug Administration
"What people want and the scientific reality are two different
situations," Pazdur said in an interview at the American Society of
Clinical Oncology (ASCO) meeting in Chicago.
He said there are currently "only a handful of therapies" that
target specific cancer-causing genes. Some oncologists have begun
using those drugs to treat cancers in people with the corresponding
genetic mutations, even when the drugs haven’t been approved for the
type of cancer a patient has.
When the drugs work, the results are dramatic. Tumors seem to melt
away, and advances in survival are counted in months and years, not
weeks. The transformation has led many doctors to question whether
the current practice of approving drugs based on the organ they
target needs to change.
But there have also been disappointments. Drugs made by Roche and
GlaxoSmithKline that target cancers with a mutation known as BRAF
can have a powerful, albeit transient, effect in beating back the
deadly skin cancer melanoma. These drugs do not work, however, in
patients with colon cancers driven by the same BRAF mutation,
according to a 2012 study that began to sow doubt among some
experts.
"The temptation in practice is to get the tumor sequenced, and if
something comes up for which there is an approved drug, your
clinician is tempted to try that, no matter what the tumor is. But
it might not be that simple," said Dr. Barbara Conley of the
National Cancer Institute.
As it turns out, colon cancers with BRAF mutations have another
driver mutation called EGFR. In those tumors, doctors may need to
use a combination of agents that hit both targets, , according to
new data presented at ASCO this weekend.
Dr. Bert Vogelstein, a cancer geneticist at Johns Hopkins University
in Baltimore, said there is scant evidence that matching a patient's
mutation to a targeted drug improves care.
"It's definitely an unproven assumption and we ought to test it,"
Vogelstein said.
JUMP IN GENETIC PROFILING
Oncologists interviewed by Reuters said genetic profiling of tumors
is becoming much more routine, particularly if a patient with
advanced disease hasn’t recovered with more traditional approaches.
Foundation Medicine Inc, which makes genetic profiling tests, has
seen clinical demand for its tests jump 67 percent in the first
quarter from the same period a year ago.
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Dr. Richard Schilsky, chief medical officer of ASCO and a University
of Chicago Medicine oncologist, estimates that in up to 70 percent
of such tests, doctors find a genetic mutation that can be matched
with a drug. Insurers, however, aren’t quick to cover a treatment
for an unapproved use unless there is evidence that it will work.
“They are experimenting. It's not like these therapies don't have
harms as well. They have side effects," said Jennifer Malin, medical
director for cancer drugs at health insurer Anthem Inc.
The issue will be studied more broadly in a large cancer clinical
trial launched by the NCI. It is designed to match the underlying
genetic defect driving a person's tumor with one or more of 20
approved or experimental drugs targeting that gene.
ASCO is also starting a clinical trial to gather data on how
patients fare when doctors order genetic profiles and use the data
to influence treatment. The TAPUR trial will allow these patients to
be treated with one of five FDA-approved drugs provided for free,
and their data will be collected to help answer this question.
Early results from a small Foundation Medicine-sponsored trial
presented on Sunday showed a limited benefit. Researchers at
University of Texas MD Anderson Cancer Center tested 339 patients
with very advanced cancers. For 122 patients, the team was able to
match the genetic defects in their tumors to a drug or combination
of drugs targeting those defects. They also followed 66 patients
whose cancers were not matched to a targeted drug.
The patients whose tumors were matched with a targeted drug lived 2
months longer than the unmatched patients. Dr. Jennifer Wheler of MD
Anderson, who led the study, thinks the outcome might improve if the
approach were tried in healthier patients.
But it will take large clinical studies to prove the hypothesis that
picking a patient’s therapy based on the mutation in his or her
tumor works. “It’s like everything else. The devil is in the
details,” Vogelstein said.
(Editing by Michele Gershberg and Sue Horton)
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