A Pilot Study Of Pembrolizumab And Exemestane/Leuprolide In Premenopausal Hormone Receptor Positive/Her2 Negative Locally Advanced Or Metastatic Breast Cancer (Peer).

Abstract Interim Analysis Background: Despite the success of immunotherapy in triple negative breast cancer, no approved immunotherapy is available for HR+, HER2- MBC patients. Among HR+/HER2- patients(pts), luminal subtype B pts who are more resistant to endocrine therapy, demonstrate higher tumor infiltrating lymphocytes, higher immune score, and higher expression of PD-L1 than luminal subtype A pts. In addition, estrogen is known to result in immunosuppressive microenvironment. Exemestane, as a steroidal aromatase inhibitor, provides less than 10% overall response rate in second or third line of endocrine therapy for MBC pts. This pilot study aims to observe the efficacy of a combination of exemestane, leuprolide, and pembrolizumab in pre-/perimenopausal HR+, HER2- locally advanced or MBC pts who failed front-line endocrine therapy. Methods: This single-center, nonrandomized, open-label, phase Ib/II study of exemestane/leuprolide plus pembrolizumab enrolled a cohort of endocrine resistant HR+, HER2-, pre-/perimenopausal, locally advanced or MBC pts who 1) had failed adjuvant endocrine therapy within 12 months, 2) had failed at least 2 lines of prior endocrine therapy for MBC, 3) had failed 1st line endocrine therapy within 6 months or 1st line endocrine therapy+ CDK4, 6 inhibitor within 12 months. No prior chemotherapy for locally advanced or MBC was allowed. Patients received 25mg exemestane orally daily, 3.6mg leuprolide subcutaneous injection every 28 days, and pembrolizumab 150mg IV on day 1/day 15 every 28 days. Primary objective was to estimate the efficacy of the exemestane, leuprolide plus pembrolizumab combination defined by progression-free survival (PFS) rate at 8 months. Secondary objectives included safety, objective response rate (ORR), clinical benefit rate (CBR), and PFS. Results: Of 14 pts enrolled, 6 (42.9%) received 1 line and 8 (57.1%) received 2 lines of prior endocrine therapy in the locally advanced/metastatic setting. Safety of the combination was generally consistent with known side effects of exemestane, leuprolide, and pembrolizumab and was generally manageable. Grade 3/4 adverse events in ≥1 pt included AST increase (4 pts/28.6%), ALT increase (4 pts/28.6), and hypo/hyperthyroidism (1 pt, 7.1%). Nine pts did not progress or die at 8 months (64.3% PFS rate at 8th month). In the 13 evaluable pts, 5 had confirmed partial response [PR] (ORR=38.4%), 6 had confirmed stable disease[SD, 46.2%]. The disease control rate (complete response [CR]+partial response [PR]+stable disease [SD]) was 84.6%. CBR (CR+PR+SD persisting for ≥6 months) was 76.9%. Median PFS of the evaluable pts, PR pts, SD pts, and PD pts were 10.2 months, 15.8months, 10.1 months, and 2.4 months respectively. Conclusions: Combination of exemestane, leuprolide plus pembrolizumab demonstrated a generally tolerable safety profile with numerically higher rate of transaminase elevations than reported for the individual treatments. Compared to historical data for exemestane/leuprolide or for pembrolizumab monotherapy in a similar pt population, a meaningful higher ORR and longer PFS were observed. Citation Format: I-Chun Chen, Ching-Hung Lin, Dwan-Ying Chang, Tom Wei-Wu Chen, Ming-Yang Wang, Wei-Li Ma, Yi-Ting Lin, Shu-Min Huang, Yen-Shen Lu. A pilot study of pembrolizumab and exemestane/leuprolide in premenopausal hormone receptor positive/HER2 negative locally advanced or metastatic breast cancer (PEER) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT028.