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 gene copy number as measured by in situ hybridization (ISH). HER2-low BC may respond differently to treatment than BC with no HER2 expression (HER2-0); thus, we conducted an unplanned post hoc analysis of three randomized, pivotal phase III studies (Studies 301, 304, and 305) to compare eribulin vs other chemotherapies in patients (pts) who had MBC. Pts enrolled had MBC and ≤2 (Study 301) or 2-5 (Studies 304, 305) prior lines of chemotherapy for advanced/recurrent/metastatic disease including an anthracycline and a taxane. Pts were treated with eribulin vs capecitabine (Study 301), vinorelbine (Study 304), or treatment of physician’s choice (TPC; Study 305). Median OS, median PFS, and ORR were analyzed, the latter two per RECIST (Studies 301, 305: v1.0; Study 304: v1.1) by independent imaging review. ORR was measured in the intent-to-treat population (Studies 301, 304) and in evaluable pts (Study 305). Eligible enrolled pts are shown in the Table; baseline characteristics were generally balanced between treatment arms in all studies; all pts in Study 304 were Chinese. PFS and OS outcomes were generally similar or improved with eribulin vs chemotherapy in pts with HER2-low and HER2-0 MBC, irrespective of study (Table); PFS and OS were generally similar among HER2-low, HER2-0, and HER2-positive pts randomized to eribulin. ORR for eribulin vs capecitabine was similar in Study 301 for HER2-low (8.8% vs 10.4%) and HER2-0 pts (10.1% vs 8.9%). ORR generally trended towards improvement with eribulin vs vinorelbine in Study 304 (HER2-low: 34.8% vs 22.4%; HER2-0: 24.5% vs 18.0%) and eribulin vs TPC in Study 305 (HER2-low: 18.8% vs 6.1%; HER2-0: 10.4% vs 4.0%).Table: 259PHER2Low0nOSaPFSanOSaPFSa301Eribulin11415.7; 13.1-18.14.1; 2.8-5.424815.9; 14.6-18.64.0; 3.0-4.3Capecitabine13513.5; 10.3-15.93.6; 2.7-4.223713.5; 11.8-15.54.0; 3.0-4.9HR0.91.00.81.195% CI0.7-1.20.7-1.40.6-<1.00.9-1.3304Eribulin6913.2; 11.4-21.14.1; 2.8-4.210213.5; 9.3-17.62.8; 2.7-4.1Vinorelbine6711.0; 9.9-16.93.2; 2.7-4.210014.3; 10.6-NE2.7; 1.4-2.8HR0.90.91.10.795% CI0.5-1.40.6-1.30.8-1.70.5-0.9305Eribulin12112.8; 9.1-15.73.7; 3.1-4.122213.8; 12.0-14.93.7; 3.1-4.9TPC5711.0; 7.7-NE2.1; 1.9-3.711710.2; 8.4-14.62.2; 1.9-3.3HR0.80.70.80.795% CI0.5-1.30.4-1.00.6-1.10.6-<1.0aUnits: mo; 95% CI. HR, hazard ratio; NE, not estimable. Open table in a new tab aUnits: mo; 95% CI. HR, hazard ratio; NE, not estimable. Eribulin had efficacy regardless of HER2 status, and, in HER2-low pts, had similar or numerically superior outcomes vs chemotherapy in each study..