The Investigation of serial studies to predict your therapeutic response with imaging and molecular analysis 2 (I-SPY 2), an innovative, multidrug, phase 2 breast cancer trial, has yielded positive results with the first drug to complete testing during the trial. Adding the chemotherapy, carboplatin, and the molecularly targeted drug, veliparib, to standard presurgery chemotherapy improved outcomes for women with triple-negative breast cancer, according to results from the I-SPY 2 trial, which were presented at the 2013 San Antonio Breast Cancer Symposium, December 10-14, 2013.

Women with breast cancer who are likely to benefit from chemotherapy can be given that chemotherapy first, prior to surgery, using a treatment strategy referred to as neoadjuvant therapy. With this approach, doctors and researchers can learn how the tumor responds to treatment. If, after completing neoadjuvant therapy, there is no residual invasive cancer detected in breast tissue, and after surgery to remove lymph nodes, the patient is said to have a pathologic complete response. Women with a pathologic complete response have a greater chance of long-term survival compared with women who do not have a pathologic complete response.

The I-SPY 2 trial employs an adaptive design to learn which patients respond better to which therapies as the trial proceeds. Eligible patients are randomly assigned to standard neoadjuvant chemotherapy, including paclitaxel followed by anthracycline-based chemotherapy, or they receive paclitaxel in combination with a novel agent followed by anthracycline-based chemotherapy before surgery. Each woman has a 4-to-1 chance of being randomized to receive a novel agent.

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“As the trial progresses, [we learn] how different tumor subtypes respond to distinct novel agents, and through the adaptive trial design, women are assigned with higher probability to therapies that are performing better for patients with their subtypes,” said Hope S. Rugo, MD, professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California at San Francisco Helen Diller Family Comprehensive Cancer Center.

Rugo reported trial results from 1 of 7 experimental treatment arms that have been evaluated to date and the concurrently randomized controls. These data demonstrate that patients with triple-negative breast cancer were significantly more likely to have a pathologic complete response if they received veliparib and carboplatin in combination with standard therapy than if they received standard (control) therapy alone.

“These results predict that the veliparib/carboplatin regimen is highly likely to be superior to the control regimen for triple-negative breast cancer in a phase 3 trial,” said Rugo.

The estimated pathologic complete response rates for patients with triple-negative breast cancer were 52% for those receiving veliparib, carboplatin, and standard paclitaxel followed by anthracycline-based chemotherapy, and 26% for patients treated with control therapy. These respective percentages were 33% and 22% for patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.