Yale Cancer Center Study Shows Immunotherapy Drug Combination Improves Response in HER2-Negative Breast Cancer Including a Subset of Estrogen Receptor Positive Cancers

Partner | Cancer Centers | <b>Yale Cancer Center</b>

In a new study by researchers at Yale Cancer Center, combining the immunotherapy drug durvalumab and PARP-inhibitor olaparib with chemotherapy improved response to treatment for women with high-risk, HER2-negative breast cancer, including a subset of estrogen receptor positive cancers. The findings, part of the I-SPY2 clinical trial, were published today in the journal Cancer Cell.

“We found a molecularly defined subgroup of ER-positive patients with breast cancer who benefited significantly from an immune oncology drug added to chemotherapy, similar to what has been seen in triple negative breast cancer,” said Lajos Pusztai, MD, DPhil, Professor of Medicine (Medical Oncology) and Director of Breast Cancer Translational Research at Yale Cancer Center and lead author of the study. “The results are very encouraging as they provide continued evidence for immunotherapy for women diagnosed with this potentially deadly disease.”

Durvalumab is a checkpoint inhibitor immunotherapy engineered to unleash immune system T cells against tumors by inhibiting a protein on the surface of T cells called PD-1. PARP inhibitor drugs, such as olaparib help to repair DNA damage caused by chemotherapy.

Investigators studied results from a small, randomized, phase II, I-SPY2 clinical trial of stage II/III HER2-negative breast cancer. Seventy-three patients were treated with durvalumab and olaparib followed by standard neoadjuvant chemotherapy, while 299 patients received standard-of-care. The findings showed patients receivingdurvalumab plus olaparib improved estimated pathological complete response rates (over control) from 20% to 37% in HER2-negative cancers, from 14% to 28% in HR-positive/HER2-negative cancers, and from 27% to 47% in Triple Negative Breast Cancer (TNBC).

I-SPY (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis) 2 is a multicenter phase 2 trial to evaluate novel agents as pre-surgical therapy for breast cancer. The study is a collaboration among 20 U.S. cancer research centers, the U.S. Food and Drug Administration, and the Foundation for the National Institutes of Health Cancer Biomarkers Consortium. Lead support for I-SPY 2 came from the Quantum Leap Healthcare Collaborative.

“The next step for this research is to conduct a larger, randomized validation trial,” added Pusztai. “We hope the results will be practice changing in treatment for this disease.”

Funding for this study was provided by AstraZeneca.