(Reuters) – Women with triple negative breast cancer whose neoadjuvant therapy included the experimental drug veliparib (AbbVie Inc) had a significantly better response than those who got a standard chemotherapy regimen, according to data from a clinical trial.
Patients with 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 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 researchers select the right group of patients to enroll into late stage clinical trials, potentially cutting the cost of bringing new drugs to market.
“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 in 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.
“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 setting in high-risk patients. Rugo was presenting the portion of the trial that involved veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor with chemosensitizing and antitumor activities.
In that arm of the study involving 71 high risk patients with triple negative breast cancer, the researchers found an estimated pathologic complete response in 52% of women who were treated with veliparib plus carboplatin and paclitaxel. That compared with a 26% pathologic complete response rate in those who just got standard paclitaxel. Both groups also received anthracycline-based chemotherapy prior to surgery.
Triple-negative tumors – about 15% 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 veliparib, 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.”