Download Groups Push for Pediatric Cancer Drug Testing

Published OnlineFirst March 6, 2014; DOI: 10.1158/2159-8290.CD-NB2014-033
Given Imaging
NEWS IN BRIEF
PillCam COLON has been approved for use in
patients who have incomplete colonoscopies.
Once swallowed, the capsule sends video images
to physicians for review.
Measuring 12 × 33 millimeters
(0.47 × 1.3 inches) with a battery life of
10 hours, the capsule, when in motion,
wirelessly transmits 35 images per second to a recording device worn by the
patient. The images are uploaded to a
computer and rendered into a video for
the physician’s review. Although there
is no need for sedation or medical
supervision, more bowel preparation is
required than with colonoscopy.
“This is an exciting new device, and I
expect doctors will start using it as soon
as it is available in patients who have
incomplete colonoscopies,” says Marta
Davila, MD, a professor of medicine
and head of the colon cancer screening program in the Cancer Prevention
Center at The University of Texas MD
Anderson Cancer Center in Houston.
The manufacturer estimates about
750,000 U.S. patients have an incomplete
colonoscopy each year due to a long or
tortuous colon, history of abdominal
surgery, or advanced diverticular disease.
They often must undergo additional
procedures, such as CT colonography
or barium enema, resulting in further
discomfort, risks, and costs. PillCam
COLON is better tolerated by patients,
and Given Imaging anticipates it will
cost slightly more than $500, the approximate price of the company’s similar
device for viewing the small intestine.
Despite the colon capsule’s limited
indication, Davila expects some patients
may ask for it in place of other screening tests—and physicians may justifiably comply. “Although the capsule is
not currently FDA-approved for screening, it might still be an option for
patients who are unwilling or unable
to undergo colonoscopy,” says Davila.
“This might motivate them to finally
get tested.” If the capsule finds polyps,
however, a patient will still need a
colonoscopy to remove them.
PillCam COLON’s approval was
based on an analysis of hyperplastic
polyps and adenomas at least 6 millimeters in size from a 16-site study of
884 patients at average risk for colon
cancer. It showed that the positive percent agreement for PillCam COLON
and optical colonoscopy was 69% and
negative percent agreement was 81%.
Risks included capsule retention, aspiration, and skin irritation.
Later this year, Given Imaging plans
to seek expanded approvals for PillCam
COLON in patients with comorbidities
who have a higher risk for colonoscopy
complications and in patients being
evaluated for inflammatory bowel disease, says Homi Shamir, the company’s
president and CEO. The company also
plans to test the capsule as a screening
tool for colorectal cancer.
PillCam COLON will have a phased
launch in a limited number of locations.
The device is commercially available
in more than 80 countries, including
Japan, China, Canada, and the UK. ■
Groups Push for Pediatric
Cancer Drug Testing
A prominent UK university is leading a call for changes to the European
Union’s drug regulatory system that
would strengthen legislation regulating whether new cancer drugs potentially effective for adult cancers need
to be tested in children.
Under current European rules,
pharmaceutical companies can apply
for—and frequently receive—waivers
exempting them from fi ling pediatric
investigation plans (PIP) for drugs
approved for cancers that do not affect
children. The Institute of Cancer
Research (ICR) wants the European
Commission to deny such waivers
because many drugs target mutations
that may occur in both adult and pediatric tumors, such as ALK and EGFR.
“Cancer drugs are almost never
specifically developed for pediatric
tumors if the tumor types don’t occur
in adults,” says Louis Chesler, MD,
PhD, reader in pediatric solid tumor
biology and therapeutics at the ICR,
part of the University of London, and
a pediatric oncologist at London’s
Royal Marsden hospital. “If the rule
were changed to say that the molecule
or pathway targeted by the drug—and
not the specific tumor types—is what
matters for cancer drug development,
then a drug effective for lung cancer
in adults, for example, might become
available for a different pediatric
cancer with a change in the same
molecular target or pathway.”
According to data collected by the
ICR and the European Consortium
for Innovative Therapies for Children
with Cancer, based in France, 26 of the
28 cancer drugs approved for adults in
Europe since 2007 have a mechanism
of action relevant to pediatric tumors.
However, 14 of them were exempted
from pediatric testing because the specific tumor types they were approved
to treat do not occur in children.
“There is some reticence on the part
of companies in Europe to develop
detailed PIPs when little is known about
the potential toxicities, or the recommended dose, in children,” says Gregory
Reaman, MD, associate director for
oncology sciences in the U.S. Food and
Drug Administration’s (FDA) Office of
Hematology and Oncology Products.
The FDA similarly grants waivers for
pediatric testing of adult cancer drugs,
when appropriate, but also offers
companies an additional 6 months
of market exclusivity for voluntarily
pursuing trials of drugs developed for
adult cancers in children when a scientific and clinical rationale exists, says
Reaman. However, instead of requiring
a detailed and complete plan up front,
the FDA can issue a written request
to companies to start a phase I trial
based on current research.
“By doing these phase I studies early
and getting some preliminary data,” he
says, “we may be able to inform the deliberations and the PIP process in Europe.”
The U.S. system has led to important pediatric approvals over the
past several years, says Reaman. For
example, imatinib (Gleevec; Novartis)
was approved to treat chronic myelogenous leukemia as well as Philadelphia
chromosome–positive acute lymphoblastic leukemia in both adults and
children, while denosumab (Xgeva;
Amgen) was approved to treat giant
cell tumor of the bone in adults and
skeletally mature adolescents.
The ICR is urging the European
Medicines Agency (EMA) to pursue
a similar cooperative strategy with
drug companies in Europe. “The
development of cancer drugs for small
patient populations is commercially
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Published OnlineFirst March 6, 2014; DOI: 10.1158/2159-8290.CD-NB2014-033
NEWS IN BRIEF
challenging in general, not only for
children’s cancers,” says Chesler. “To
encourage commercial development,
the EMA should consider creative and
more robust ways of working with
pharma, academia, and government to
make the PIP scheme more efficient.”
The FDA and the EMA already share
information and communicate regularly
about promising drugs, says Reaman.
“It’s possible for the FDA and the
EMA to require studies that may
be different but complementary to
increase the amount of useful information available,” he says. ■
Idelalisib, Ibrutinib Show
Benefits in CLL
Two recently published trials promise to transform treatment of chronic
lymphocytic leukemia (CLL), researchers say, potentially ending the need for
chemotherapy in this disease.
In a study published in January in
The New England Journal of Medicine,
researchers found that idelalisib
(Gilead), when added to the standard treatment rituximab (Rituxan;
Genentech), is more effective than
rituximab alone for patients with CLL
who were not considered good candidates for chemotherapy (N Engl J Med
2014;370:997–1007).
Idelalisib targets the activity of
the δ isoform of PI3 kinase (PI3K).
CLL cells are dependent on this PI3K
isoform, but it is not expressed in
most other cells, so targeting it is an
effective way to attack CLL without
causing debilitating side effects, says
lead researcher Richard Furman, MD,
director of the CLL Research Center
at Weill Cornell Medical College and
a hematologist/oncologist at New
York-Presbyterian/Weill Cornell Medical Center, both in New York, NY.
In the trial, the drug extended progression-free survival, and improved
response rates and overall survival.
Researchers stopped the trial early so
that patients in the control arm could
start idelalisib and share the benefits.
The results were particularly striking,
Furman says, because the patients had
comorbidities such as kidney dysfunction or bone marrow failure, and were
no longer eligible for chemotherapy.
“I never assumed we’d find an overall survival advantage,” he says. “I was
shocked when we saw that.”
Furman was also involved in a trial
published in December in The Lancet
Oncology that showed the effectiveness of
the tyrosine kinase inhibitor ibrutinib in
untreated patients over age 65 (Lancet
Oncol 2014;15:48–58). Ibrutinib (Imbruvica), jointly marketed by Pharmacyclics
of Sunnyvale, CA, and Janssen Biotech
of Raritan, NJ, targets Bruton’s tyrosine
kinase, which is specific to B cells.
Ibrutinib was approved by the U.S.
Food and Drug Administration (FDA)
on February 12 for use in patients
with CLL who have received at least
one previous therapy; it was approved
in November 2013 to treat mantle cell
lymphoma. The FDA is expected to
issue a decision on idelalisib for use in
CLL this spring.
Furman, who’s been involved in
trials of 10 different kinase inhibitors,
says the approval of these two “home
run” drugs suggests that the majority of CLL patients may never need
chemotherapy again.
“I would not give anyone chemotherapy, period,” he says.
Other researchers say that chemotherapy may still play a role in treatment, particularly in combination
with a targeted therapy, in patients
diagnosed in middle age or younger.
Doctors don’t yet know whether
ibrutinib will keep CLL in check for
decades, says Jennifer R. Brown, MD,
PhD, director of the CLL Center at
Dana-Farber Cancer Institute and
an associate professor of medicine at
Harvard Medical School, both in
Boston, MA. That’s why they may want
to combine it with chemotherapy.
“In younger, fit patients who can handle chemotherapy pretty well, it might
be possible to combine novel agents
with chemo immunotherapy and maybe
that would move us toward cure,” says
Brown, who is leading some combination trials for young patients now.
For his part, Furman says the publication of these two trials marks the
culmination of his life’s work.
“These drugs bring an end to
clinical research in a lot of regards,” he
says. “It’s a very good reason to be out
of work.” ■
NOTED
• The U.S. Preventive Services Task Force
recommended against using vitamin E
and b-carotene supplements to reduce
the risk of cancer and cardiovascular disease because evidence suggests they
offer no net benefit (Ann Intern Med 2014
Feb 25 [Epub ahead of print]). In addition,
the group found adequate evidence that
β-carotene supplements increase the risk
for lung cancer among people at increased
risk of the disease, such as smokers.
• For the first time, the U.S. Food and
Drug Administration (FDA) halted the
distribution and sale of certain tobacco
products currently on the market, the
authority for which was granted to the
agency under the 2009 Family Smoking
Prevention and Tobacco Control Act.
Manufactured by Jash International, the
four products—Sutra Bidis Red, Sutra
Bidis Menthol, Sutra Bidis Red Cone, and
Sutra Bidis Menthol Cone—were found
to be not substantially equivalent to
tobacco products commercially marketed as of February 15, 2007, and the
company did not meet FDA requirements to continue selling them.
• GlaxoSmithKline discontinued the
manufacture and sale of Bexxar (tositumomab), a radio-immunotherapy with the
radioactive isotope iodine-131 approved
in 2003 for patients with CD20-positive
relapsed or refractory non-Hodgkin lymphoma, due to relatively low profitability.
• Astellas Pharma Inc. and Aveo Oncology
terminated their agreement to develop
Aveo’s tivozanib for the treatment of
breast and colon cancers. In December,
the companies announced that the drug
was not likely to meet its primary endpoint in a phase II colon cancer trial.
• Pharmaceutical giant Roche secured an
injunction in an Indian court that prevents two companies from comparing
their biosimilars to its breast cancer
drug Herceptin (trastuzumab). The court
ruled that Mylan and Biocon, which developed Hertraz and CANMab, respectively,
cannot refer to Herceptin or its manufacturing process, safety, effectiveness, or
sales when marketing their products.
Mylan and Biocon received approval from
Indian drug regulators last fall to market
generic versions of Herceptin.
For more news on cancer research, visit Cancer Discovery online at http://CDnews.aacrjournals.org.
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Groups Push for Pediatric Cancer Drug Testing
Cancer Discovery 2014;4:381-382. Published OnlineFirst March 6, 2014.
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