Immunotherapy drug combination improves response in HER2-negative breast cancer, including a subset of estrogen receptor positive cancers

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A study by researchers at Yale Cancer Center shows that 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 lead author Lajos Pusztai, professor of medicine (medical oncology) and director of breast cancer translational research at Yale Cancer Center. “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 receiving durvalumab 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.

Funding for this study was provided by AstraZeneca.

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