A Yale Cancer Center clinical trial combining the immune checkpoint inhibitor (durvalumab/MEDI4736) with chemotherapy as preoperative treatment for early stage triple negative breast cancer disclosed a 71% pathologic complete response to the combination treatment in the initial phase I trial. By comparison, chemotherapies alone produce a pathologic complete response rate of only around 35-40% for women with triple negative breast cancer (TNBC). The clinical trial data will be presented at the American Society of Clinical Oncology meeting on Sunday, June 4.
"The preliminary efficacy result from a Phase I/II trial suggests very high activity, with a 71% pathologic complete response rate. This is important because women with breast cancer who achieve complete response have excellent long-term survival," said Lajos Pusztai, MD, lead author of the study.
About 10% of breast cancers are found to be triple negative, where the breast cancer cells have tested negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-). "There is an unmet need for new treatment options to increase cure rates for women with TNBC. By combining chemotherapy with immunotherapy in this clinical trial, we are extending our options for treatment, and finding new hope," said Dr. Pusztai.
The phase I part of the trial sought to determine the safety and tolerability of durvalumab in combination with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC). There were no dose-limiting toxicities with the combination; therefore the full dose of neoadjuvant chemotherapy can be given together with the full dose of durvalumab. Among the 7 patients in the Phase I trial, 5 achieved pathologic complete response, 1 had partial response with residual disease, and 1 had extensive residual cancer. This corresponds to a pathologic complete response rate of 71%. The phase II clinical trial is now open for patient accrual at Yale Cancer Center.