Neoadjuvant therapy with an aromatase inhibitor and durvalumab in postmenopausal patients with hormone receptor-positive breast cancer.

[PURPOSE] Hormone receptor-positive (HR+), HER2-negative breast cancer represents the most common subtype of breast cancer and is characterized by a risk of late recurrence. Neoadjuvant endocrine therapy with aromatase inhibitors (AIs) is a well-tolerated option in postmenopausal women; however, strategies to enhance its efficacy are needed. Combination of AI with immunotherapy is a promising approach. We evaluated the efficacy and safety of combining an AI with the anti-program death ligand 1 antibody durvalumab in the neoadjuvant setting.

[METHODS] This single-arm, phase II study used a Simon two-stage design. Postmenopausal patients with early-stage HR+/HER2-negative breast cancer received durvalumab every 4 weeks plus daily AI for 6 months prior to surgery. The primary endpoint was the achievement of a modified Preoperative Endocrine Prognostic Index (mPEPI) score of 0.

[RESULTS] Seventeen patients were enrolled and received durvalumab plus daily AI for six months before surgery. Treatment was well tolerated, with most adverse events being grade 1-2. A clinical complete response was seen in 58.8% of patients, although no pathologic complete responses occurred. Among the first 14 patients, one achieved mPEPI 0, which did not meet criteria to proceed to stage two. Overall, three patients (17.6%) achieved mPEPI 0.

[CONCLUSION] Neoadjuvant durvalumab plus AI was safe but demonstrated limited pathologic efficacy in this unselected HR + HER2-negative population. Favorable long-term outcomes support further investigation of immunoendocrine combinations in HR + HER2-negative breast cancer in biomarker-selected subgroups.

[TRIAL REGISTRATION] NCT03874325. Date of registration. 12-03-2019.