Background: HR+ breast cancer has a long dormancy and steady rate of recurrence over decades from initial diagnosis. It is a misconception to think that HR+ disease has good prognosis since long term PFS and OS are only a few percent better for HR+ disease compared with HR- disease over a follow up of 20 years. Neoadjuvant endocrine therapy has been shown to be equivalent to chemotherapy but less toxicity. Aromatase inhibitors have also been shown to have immunomodulatory activity. In order to improve short term and long term outcomes, we started an investigator-initiated study using anastrozole plus the anti-PD-L1 antibody durvalumab in the neoadjuvant treatment of HR+/HER2- breast cancer. Methods: This is an open label, phase II with safety run-in trial conducted at Moffitt Cancer Center. The primary objective is modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0. Secondary objectives are clinical response rate, pathologic response rate, recurrence free survival. Correlative objectives include phenotypic changes in immune cells and cytokine patterns pre-, during- and post-treatment. Inclusion criteria include postmenopausal females, ECOG 0-1, HR+ with Allred score of 6 to 8, HER2-, cT2-cT4, any N, M0, appropriate lab values, agreeing to research biopsies. Exclusion criteria include multicentric disease, bilateral disease, autoimmunity or inflammatory disease, use of immunosuppressant, known HIV, Hep B/C infection, history of TB, h/o interstitial lung disease or pneumonitis, clinically significant cardiovascular disease, mean QTcF > 470 ms. Patients will receive anastrozole 1 mg PO daily for 6 months concurrently with durvalumab 1500 mg IV every 4 weeks for 6 cycles, followed by definitive surgery. Results: This is a trial in progress. However, limited preliminary results will be presented. Conclusion: The combination of anastrozole and durvalumab may lead to improved mPEPI score in the short term and improved RFS in the long term.

Citation Format: Hung T Khong, Dawn N Goodridge, Nazanin Khakpour, M. Catherine Lee, Christine Laronga, Avan J Armaghani, Aixa E Soyano-Muller, Hyo Han, Hatem Soliman, Ricardo Costa, Loretta Loftus, Susan J Hoover, John V Kiluk, Zena Jameel, Brian J Czerniecki. A phase II trial with safety run-in of neoadjuvant therapy with an aromatase inhibitor in combination with durvalumab (MEDI4736) in postmenopausal patients with hormone-receptor-positive (HR+) breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-15-01.