Angela DeMichele, MD, MSCE, Discusses Future Directions of the Phase 2 I-SPY2 Trial in Early Breast Cancer

Angela DeMichele, MD, MSCE, discussed the results of the phase 2 I-SPY2 trial in patients with early breast cancer

CancerNetwork® spoke with Angela DeMichele, MD, MSCE, co-leader of the Breast Cancer Research Program, co-director of 2-PREVENT Breast Cancer Translational Center of Excellence, and Alan and Jill Miller Professor in Breast Cancer Excellence at Penn Medicine in Philadelphia, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting about the phase 2 I-SPY2 trial (NCT01042379).1 This platform trial was designed to evaluate pathological complete response from novel adjuvant systemic therapy options in patients with early breast cancer across various tumor and molecular subtypes. Specifically, DeMichele talked about additional results that will be published later this year which will outline how patients will be treated going forward given the updated design of I-SPY2.


I want to draw your attention to a pivotal paper that we just published in Cancer Cell.2 Denise Wolf, PhD, is the first author, and that outlines this entirely new way of classifying tumors. Over the summer, you’ll be hearing about how we now are changing the [I-SPY2] trial to enable patients who come in to get new profiling. Patients are then told about their profile, and they start a series of treatments that are matched to that profile. As they move through the trial, if the first treatment isn’t working, as well as we’d hoped, they have the opportunity to go on to another drug and another drug. In a traditional clinical trial, the patient sends their consent, and they get one treatment. When that treatment ends, and they go to surgery. In the new version of I-SPY2.2, we now have the ability to give patients multiple opportunities to find drugs that will work up front at the time that they’re diagnosed.


  1. Huppert LA, Rugo HS, Pusztai L, et al. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. J Clin Oncol. 2022;40(suppl 16):504. doi:10.1200/JCO.2022.40.16_suppl.504
  2. Wolf DM, Yau C, Wulfkuhle J, et al. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell. 2022;40(6):609-623.e6. doi:10.1016/j.ccell.2022.05.005