I-SPY 2: a Neoadjuvant Adaptive Clinical Trial Designed to Improve Outcomes in High-Risk Breast Cancer

The I-SPY 2 trial is an adaptive clinical trial platform designed to improve outcomes in high-risk breast cancer patients by testing new drugs in the neoadjuvant setting. The intent of this review is to discuss background, study structure, innovation, and outcomes of the I-SPY 2 trial. I-SPY 2 evaluates new agents combined with standard therapy with pathologic complete response (pCR) as the primary endpoint. I-SPY-2 uses clinical biomarkers to classify breast cancer into 10 subtypes, with Bayesian adaptive randomization to allow individualized patient assignment to therapy arms to maximize treatment effects. A total of 7 drugs have graduated from I-SPY 2. Multiple new agents are currently in active enrollment in I-SPY 2. I-SPY 2 uses an individualized approach in clinical trial design to improve high-risk breast cancer outcomes. The purpose of this review is to encourage further research and innovation in this area and bring more precise treatment options to breast cancer patients.