Positive Results for Drug Combo in I-SPY 2 Trial

Adding a combination of veliparib plus carboplatin to standard neoadjuvant chemotherapy improved outcomes for women with triple-negative breast cancer participating in the I-SPY 2 trial, an adaptive, phase II breast cancer trial with multiple experimental treatment arms. The findings were reported last month at the 2013 San Antonio Breast Cancer Symposium in Texas.

“The degree of benefit was exciting and surprising, because we've struggled with how to treat patients with sporadic triple-negative disease and understanding who benefits from treatment,” says Hope S. Rugo, MD. Rugo is co-principal investigator of the veliparib study, and professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center. “We may really be able to define a group of patients that benefit from this approach and then be able to study it in a phase III trial that's biomarker driven,” she adds.

Rugo and co-principal investigator Olufunmilayo Olopade, MD, director of the Center for Clinical Cancer Genetics at Illinois's University of Chicago, randomly assigned 71 patients to receive veliparib plus carboplatin in addition to paclitaxel. Of that group, 38 had triple-negative disease and 33 had hormone receptor (HR)–positive and HER2-negative disease. Another 44 patients with HER2-negative disease were concurrently assigned to standard neoadjuvant treatment of paclitaxel followed by anthracycline-based chemotherapy, creating a control group.

Women who received the veliparib plus carboplatin combination plus standard therapy were significantly more likely to have a pathologic complete response (52%) than women who received standard therapy alone (26%), investigators reported. Based on those results, researchers calculated a 92% Bayesian predictive probability that the novel combination plus standard therapy would be statistically superior to standard therapy alone for women with triple-negative disease in a phase III trial enrolling 300 patients. If only HER2-negative patients were enrolled in a phase III trial, the prediction for success drops to 55%.

“This means we have information that allows us to create a very well-designed, high likelihood of success phase III trial,” says Rugo. “It shows that progress can be much faster and the benefits can be felt by patients much earlier than what we've seen to date.”

The I-SPY 2 trial is innovative for its adaptive design, in which the goal is to identify biomarker signatures in order to match experimental drug regimens with patients who would most benefit from them. Whereas a traditional trial tests one experimental drug with a control group for the length of the trial, I-SPY 2 simultaneously compares multiple novel agents with one control arm and continuously assesses patients' progress in order to match individual subtypes with the most effective therapies.

Veliparib plus carboplatin is the second arm of the I-SPY 2 trial to report positive results. In early December, Puma Biotechnology reported that an experimental regimen containing neratinib added to standard therapy had a high probability of success in a phase III trial for patients with HER2-positive/HR-negative disease. Full results of that trial will be presented at a future scientific meeting.