129P Phase II study of pembrolizumab and nab-paclitaxel in HER2-negative metastatic breast cancer: Hormone receptor-positive cohort

Abstract

PD-1/PD-L1 checkpoint blockade in combination with chemotherapy has improved outcomes in triple-negative breast cancer, but its role in hormone receptor-positive (HR+) metastatic breast cancer (MBC) is less clear. We report the results of the HR+ cohort of a HER2-negative MBC trial. Prospective phase 2 trial where 20 HR+/HER2- MBC patients (pts) received nab-paclitaxel (A) (100mg/m2 IV d1/8, q 3 wks) and pembrolizumab (P) (200mg IV d1, q 3 wks, starting with cycle 2). Eligibility: ER/PR ≥1%, HER2 negative, maximum of 2 lines of cytotoxic therapy for MBC, pts could have received prior endocrine and/or targeted therapy. Primary endpoint: best overall response rate (BORR) by RECIST v1.1; secondary endpoints: safety, PFS, clinical benefit rate (CBR), duration of response (DOR), and overall survival (OS). Biomarker analyses are ongoing. In this 20-patient cohort, the median age was 56 (34-75), median lines of cytotoxic chemotherapy was 1 (0-2), 70% (14/20) were ER>10%, 80% (16/20) received prior hormone therapy, and 60% (12/20) received prior CDK 4/6 inhibitors. BORR was partial response (PR) in 5/20, stable disease (SD) in 7/20, and progressive disease (PD) in 7/20. CBR was 35% (7/20). Median PFS was 5.6 mos (95%CI 2.07-8.18), median OS 15.7 mos (95%CI 3.88-27.70) and median DOR was 3.9 mos (95%CI 2.07-not yet reached). Out of 5 pts who achieved PR, 4 (80%) received prior CDK 4/6 inhibitors. The most common related adverse events (AE) were anemia (50%), diarrhea, nausea and ALT abnormalities (40% each). 14 pts experienced grade 3 AEs, the most common being neutropenia, 1 pt had grade 4 AEs (pneumonitis, blood/lymphatics, hyponatremia), and no grade 5 AEs.Table 129P:Outcomes in HR+/HER2- MBCHR+/HER2 cohort (n=20)CR0 (0%)PR5 (25%)SD7 (35%)Not evaluable1 (5%)CBR (PR+SD>6mos)7 (35%)mDOR3.9 mosmPFS5.6 mosmOS15.7 mos Open table in a new tab P plus A was efficacious with PR in 5/20 and SD in 7/20 pts with a manageable toxicity profile. Importantly, responses were observed in patients previously treated with CDK 4/6 inhibitors. Further investigation of this regimen in HR+/HER2- MBC is warranted.