Abstract P1-03-02: Efficacy of eribulin mesylate in HER2-low and HER2-0 metastatic breast cancer (MBC): Results from an analysis of two phase 3 studies
Authors: Twelves Chris , Kaufman Peter A. , Awada Ahmad , Im Seock-Ah , Lalayan Bagrat , Xie Ran , Vahdat Linda T. , Cortés Javier 
Published: March 2023

Abstract
Background: Breast cancer (BC) with low-level HER2 expression (HER2-low) is defined by an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification or excess HER2 gene copy number, as measured by in situ hybridization (ISH). This represents approximately half of patients with BC overall (estimated as 55% for hormone-receptor positive [HR+] BC and 38% for triple-negative breast cancer [TNBC]; Scott, ASCO, 2021). Some data suggest that patients with HER2-low BC may respond differently to treatment than those whose BC has no HER2 expression (HER2-0). In this post hoc unplanned analysis, we analyzed data from two pivotal phase 3 studies (Studies 305 and 301) comparing eribulin with other chemotherapeutic agents (treatment of physician’s choice and capecitabine, respectively [“control”]) in patients with both HER2-low and HER2-0 MBC. Methods: Patients with MBC, 2–5 (Study 305) or &lt; 2 (Study 301) prior lines of chemotherapy for advanced/metastatic disease, and who had received an anthracycline and a taxane, were analyzed. HER2-expression status was determined by IHC and/or ISH assays. Median progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method adjusted by study; comparisons of PFS and OS between treatment groups were performed using stratified (by prior capecitabine use, geographic region, and study) log-rank tests. Hazard ratios were estimated by a stratified Cox model. For each study, median PFS and OS were also calculated for HR+ and TNBC subgroups. Results: Baseline characteristics were generally balanced between treatment groups among patients with HER2-low (n=427) and HER2-0 (n=824) BC. Patients with HER2-low or HER2-0 BC showed trends toward benefit with eribulin treatment. In patients with HER2-low and HER2-0 BC, median OS was longer with eribulin vs control (15.1 vs 12.0 months and 15.2 vs 12.5 months, respectively); median PFS by independent imaging review (IIR) was also longer with eribulin vs control (4.0 vs 3.1 months and 3.9 vs 3.1 months, respectively). Objective response rate (ORR) by IIR was also higher with eribulin vs control in patients with HER2-low and HER2-0 BC (13.7% vs 9.2% and 10.2% vs 7.4%, respectively). In a separate analysis, median OS was longer with eribulin vs capecitabine in patients with TNBC and HER2-low and HER2-0 (15.4 vs 10.3 months and 14.4 vs 8.9 months, respectively). Conclusions: In this post hoc analysis, treatment with eribulin demonstrated trends toward improved OS, PFS, and ORR compared with chemotherapy controls in patients with HER2-low or HER2-0 MBC. Funding source: This trial was sponsored by Eisai Inc., Nutley, NJ, USA. Medical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA, USA, and was funded by Eisai Inc., Nutley, NJ, USA.
Citation Format: Chris Twelves, Peter A. Kaufman, Ahmad Awada, Seock-Ah Im, Bagrat Lalayan, Ran Xie, Linda T. Vahdat, Javier Cortés. Efficacy of eribulin mesylate in HER2-low and HER2-0 metastatic breast cancer (MBC): Results from an analysis of two phase 3 studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-03-02.