Dec 13 Women with an especially deadly type of
breast cancer who received a treatment regimen containing an
experimental AbbVie Inc drug prior to surgery are
likely to have a significantly better response than those who
get a standard chemotherapy regimen, according to data from a
Patients with so-called triple negative breast cancer, who
tend to be younger and have a very poor prognosis, appeared to
have double the response rate to the regimen containing AbbVie's
veliparib in a new type of study that exploits advances in
molecular understanding of the disease, researchers found.
The trial dubbed I-SPY 2 is another step toward developing
more personalized treatments. Its design allows researchers to
continuously monitor how patients respond as the trial
progresses and move patients into arms of the study testing
drugs from which they are more likely to gain benefit.
This type of trial should help companies select the right
group of patients to enroll into larger, more traditional late
stage clinical trials, potentially cutting the cost of bringing
new medicines to market.
Drugmakers are under increasing pressure to cut the cost of
new medicines that put a huge burden on healthcare systems. One
way to do that would be through more efficient, alternative
testing methods that lead to fewer trial failures.
"It's a very nimble trial design that allows you to enroll a
fairly small number of patients and come to a fairly high
certainty of success (in later larger trials) in a specific
subset of patients," explained Dr. Hope Rugo, who presented the
data at the San Antonio Breast Cancer Symposium on Friday.
If a drug combination starts to look like it is working
better on patients with one type of breast cancer, the trial
design allows for more patients with that type of cancer to move
into that arm of the study, said Rugo, director of breast
oncology and clinical trials education at the UCSF Helen Diller
Family Comprehensive Cancer Center in San Francisco.
The U.S. Food and Drug Administration, which signed off on
the trial design, has said that if a study drug helps cure
significantly more cancers, it could be given a provisional type
of accelerated approval.
FASTER DEVELOPMENT, REDUCED COST
"If we can get a better idea of who benefits early, it's
going to be an enormous change in the way we test new agents,
and not just for breast cancer but for other malignancies as
well," Rugo said.
"You could avoid doing a 3,500 patient trial in a group of
patients who you thought might benefit but don't," she said.
"We'll be able to get the drugs to the patients who need them
much more quickly and at reduced cost."
The I-SPY program is testing a variety of experimental
medicines from several drugmakers in the neoadjuvant, or
pre-surgery, setting in high-risk patients. Rugo was presenting
the portion of the trial that involved the AbbVie drug.
In that arm of the study involving 71 high risk patients,
the researchers were testing to see whether the treatment, given
before surgery, could eliminate any evidence of invasive cancer
in breast tissue and lymph nodes removed during subsequent
surgery - a measurement known as pathologic complete response
They found an estimated PCR in 52 percent of women who were
treated with AbbVie's veliparib plus the chemotherapies
carboplatin and paclitaxel. That compared with a 26 percent PCR
rate in those who just got standard paclitaxel. Both groups also
received anthracycline-based chemotherapy prior to surgery.
"If we can increase the number of patients who have no
invasive cancer, we expect that this will translate into better
survival," Rugo said.
Most breast cancer tumors are estrogen-receptor positive,
fueled by the hormone estrogen. About 20 percent are
HER2-positive, meaning a protein called HER2 is prevalent. A
third type is driven by the hormone progesterone. All of these
have potentially effective treatment options even after
Triple-negative tumors - about 15 percent of breast cancers
- lack estrogen, progesterone or HER2 receptors needed for most
drugs to work. If the tumor does not respond to chemotherapy,
there are currently no alternatives and the typical survival
rate after recurrence is less than two years.
More women treated with veliparib and carboplatin dropped
out of the study due to side effects, whereas discontinuations
in the control arm were primarily due to disease progression.
Rugo said she looked forward to further study of the AbbVie
drug, noting that the trial design did not separate which
effects were due to veliparib and which to carboplatin.
However, she said, the doubling of response rates was "very
encouraging to us and suggests that veliparib is playing an
important role in the enhanced response that we're seeing."