Randomized phase II study of eribulin mesylate (E) with or without pembrolizumab (P) for hormone receptor-positive (HR+) metastatic breast cancer (MBC).

Abstract

1004 Background: Studies of checkpoint inhibitor monotherapy show only modest activity in HR+ MBC. We report data from the first randomized study comparing E plus P versus E alone in HR+/HER2- MBC. Methods: Eligible patients (pts) had HR+/HER2- MBC, ≥2 lines of hormonal therapies and 0-2 lines of chemotherapy for MBC. Pts were randomized 1:1 to E 1.4mg/m2 intravenously (IV) on d1 and d8 with P 200 mg/m2 IV on d1 of a 21-day cycle (Arm A) or E alone (Arm B). At time of progression, pts in arm B could crossover and receive P alone. Primary endpoint was progression-free survival (PFS). Key secondary endpoints were: objective response rate (ORR) and overall survival (OS). Exploratory analyses assessed the association between PFS and PD-L1 status, tumor-infiltrating lymphocytes (TILs), neutrophil-lymphocyte ratio (NLR), tumor mutation burden (TMB), and genomic alterations by next generation sequencing on archival tissue. Results: 88 pts initiated protocol therapy; the median age was 58, median prior lines of chemotherapy 1, prior lines of hormonal therapy 2. Median follow-up was 6.3 months. Median PFS and ORR were not different between Arms A and B (PFS 4.1 vs 4.2 months p = 0.38; ORR 25% and 34% respectively (p = 0.49). 14 patients initiated crossover treatment with pembrolizumab; 1 patient experienced a PR (ORR 7%). All-cause AEs occurred in 100% of pts (G3-4, 54.6%) including 2 treatment related deaths on Arm A, both from known AEs attributed to both drugs. PD-L1 assay was performed in 65 pts: 24 (36.9%) had PD-L1 positive ( > 1% with 22C3, centrally tested) tumors. PD-L1 status, TILs, NLR, TMB, and genomic alterations were not associated with PFS (Table). Updated data, including OS and genomic results, will be presented. Conclusions: Among pts with HR+/HER2- MBC, the combination of E and P was not associated with longer PFS than E alone in the ITT or PD-L1+ population, though the PD-L1+ subgroup had very limited power to assess P benefit. Clinical trial information: NCT03051659. [Table: see text]