I-SPY2 trial yields first results on combination therapy for triple-negative breast cancer


  • Carrie Printz

Adding the chemotherapy drug carboplatin and the molecularly targeted drug veliparib to standard presurgery chemotherapy improves the outcome for women with triple-negative breast cancer, according to the first results from the I-SPY2 (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2) trial presented at the 2013 San Antonio Breast Cancer Symposium held between December 10 and 14, 2013.

This combination was the first drug to complete testing in the I-SPY2 trial, which uses an adaptive design to determine which patients respond better to which therapies as the trial progresses. Patients in the trial are randomly assigned to standard neoadjuvant chemotherapy, including paclitaxel followed by anthracycline-based chemotherapy before surgery.

One in 4 participants in I-SPY2 is randomized to receive a novel agent. As the trial continues and researchers learn how different tumor subtypes respond to different novel agents, women are assigned to therapies that have a better chance of treating their specific tumor subtype, according to Hope Rugo, MD, director of the Breast Oncology Clinical Trials Program at the University of California at San Francisco Helen Diller Family Comprehensive Cancer Center.

At the symposium, Dr. Rugo presented results from 1 of the 7 experimental treatment arms, demonstrating 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. The results indicate that the combination is likely to be superior to the control regimen in a phase 3 trial, she says.

In the trial, 71 patients enrolled in I-SPY2 were randomly assigned to receive veliparib plus carboplatin in combination with paclitaxel. The estimated pathologic complete response rates for patients with triple-negative breast cancer were 52% for those receiving this combination followed by anthracycline-based chemotherapy and 26% for patients treated with control therapy. Based on these data, researchers calculate there is a 92% probability that this therapy would be statistically superior to standard therapy for patients with triple-negative breast cancer in a 300-patient, randomized, phase 3 clinical trial, based on pathologic complete response rates.

The adaptive trial design of I-SPY2 helps researchers to identify which patients can benefit from specific therapies, reduce trial size, accelerate drug development, and avoid overtreatment, Dr. Rugo says.

The I-SPY2 trial was launched in 2010 by The Biomarkers Consortium, a public-private biomedical research partnership managed by the Foundation of the NIH, which includes the US FDA, the NIH, and major pharmaceutical companies. It is now sponsored by QuantumLeap Healthcare Collaborative.