A clinical trial called I-SPY 2 was conducted in 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 by researchers at Yale Cancer Center (YCC). I-SPY (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis) 2 is a Phase II multicenter trial to evaluate novel agents as pre-surgical therapy for breast cancer

This clinical trial gained positive results and gained evidence to change the protocol for treating breast cancer. It was proved that women with high-risk HER2-negative breast cancer treated with immunotherapy before surgery, and given a PARP inhibitor with chemotherapy, have improved treatment results. Test group findings demonstrated a higher rate of full breast and lymph node cancer eradication as opposed to chemotherapy alone. The results were part of the I-SPY 2 clinical trial.

Before surgery, doctors treated a test group of females with HER-2 negative breast cancer with chemotherapy, aiming to shrink the tumor and direct treatment following surgery. For a women’s subgroup, pre-surgery was treated with chemotherapy, resulting in any evidence of obliteration of the tumor. Clinically this is called “pathologic complete response”. In the overall study, 73 patients were treated with durvalumab, olaparib, and paclitaxel chemotherapy followed by doxorubicin/cyclophosphamide chemotherapy, while 229 patients received standard paclitaxel plus doxorubicin/cyclophosphamide treatment in the control arm. They found that women with TNBC who received the combination therapy had a PCR rate of 47% compared to those who received regular chemotherapy with an average pCR rate of 27%. It has been reported that patients with estrogen-positive / HER2-negative cancer in the experimental arm have a PCR rate of 28% compared to 14% in the control arm.

Additional findings from the study showed that tumors with a high level of immune cell infiltration recorded higher PCR levels in all subtypes and in both the treatment and control arms, but the investigators found this could be due to biomarkers that could classify the patients are more likely to benefit from combination durvalumab and olaparib care. The results of this study suggest that earlier treatment with immunotherapy drugs is of great benefit to patients with breast cancer, especially groups of patients most at risk for recurrence of cancer. Tracking those results over time will be interesting.