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 This sort of study is “the new wave,” said Dr. Otis Brawley, chief
medical officer of the American Cancer Society, who wasn’t involved
in the research. “This is the new molecular medicine," he told
Reuters Health.
Most cancer drug studies focus on a particular type of malignancy.
But projects in recent years to analyze the DNA of various cancer
types have found that certain gene mutations appear in many kinds of
tumor, and appear to play a role in driving the disease.
In the new study, researchers focused on a mutation known as BRAF
V600, which is a defect in a genetic instruction that tells a cell
when to die. It is most common in metastatic melanoma, but other
tumors harbor it as well.
The goal was to see if the drug vemurafenib, already approved for
metastatic melanoma cases with the BRAF mutation, would work in
other tumors with the same mutation.
Among 20 patients with non-small-cell lung cancer, the most common
form of lung cancer, 42 percent of patients showed signs of
responding to the drug and average progression-free survival time
was 7.3 months, researchers reported in The New England Journal of
Medicine.
The response rate was 43 percent among 18 people with either Erdheim-Chester
disease or Langerhans'-cell histiocytosis, both rare cancer-like
conditions.
Other cancers with the BRAF V600 mutation showed a far more tepid
response to the drug, sold in tablet form under the brand name
Zelboraf by F. Hoffmann-La Roche and Genentech. The companies paid
for the trial.
Similar studies are in the pipeline and could change the way cancer
is treated, Brawley said.
"It's not whether you have pancreatic cancer, or colon cancer or
lung cancer that's going to be important to the treating clinician,"
he said. "What's going to be important to the treating clinician is
what's wrong with your tumor at a molecular level."
The new research is "a proof-of-concept kind of study," he said. "We
are going to see more and more things like this - someone with colon
cancer who didn't do well with the normal treatment may get their
tumor analyzed and (one) of these small molecule drugs the FDA has
approved for some other cancer might be tried" because it shares a
similar genetic defect.
Despite the new trial’s encouraging results in lung cancer and two
other tumors, much smaller effects, or no effects, were seen in
patients with colorectal cancer, brain tumors, multiple myeloma,
anaplastic thyroid cancer or bile duct cancer.
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Dr. David
Hyman, acting director of developmental therapeutics at Memorial
Sloan Kettering Cancer Center in New York. "It's harder to draw firm
conclusions about the effectiveness of vemurafenib in these
patients."
In the cancer types with less response, Hyman noted, the BRAF V600
mutation is typically present in fewer than 5 percent of tumors that
have resisted conventional therapy and spread, so only those
patients would be candidates for the drug.
The treatment costs about $11,000 to $12,000 per month.
In a commentary in the Journal, Dr. David Hunter of the Harvard T.H.
Chan School of Public Health and Dr. Ralph D'Agostino Sr. of Boston
University caution that newer sequencing studies have found that
individual tumors can be very heterogeneous. Different parts of the
same primary tumor may have very different groups of mutations,
which would further complicate treatment with targeted drugs.
Such drugs may block one chemical pathway used by cancer cells to
grow and spread, but "if you block one route, (a tumor) can always
detour around it," which is why the benefits of vemurafenib didn't
always last, Brawley said.
"It's only a matter of time before these tumors find a way around
that blockage, some faster than others," he said. "But they're
demonstrating they can block it, and that this drug, already
approved in melanoma, has some usage in several of these diseases."
SOURCE: http://bit.ly/1NwQBqU New England Journal of Medicine,
online August 19, 2015.
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