Background: Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor, has demonstrated an overall survival benefit relative to other commonly used agents in pts with at least 2 prior MBC therapies. Primary data presented from 2 phase 2 trials, Study 206 (eribulin in HER2- pts) and Study 208 (combination eribulin + trastuzumab [TRAS] in HER2+ pts), showed clinical activity and acceptable tolerability profiles as first-line therapy (tx). Here we present prespecified efficacy data for both trials based on prior anthracycline (A) and taxane (T) use. Methods: In both studies, pts received eribulin mesylate 1.4 mg/m²IV on Days 1 and 8 of each 21-day cycle. Pts in Study 208 (HER2+ pts) also received initial TRAS (8 mg/kg IV/Day 1), followed by 6 mg/kg/Day 1 of each subsequent cycle. Response, progression-free survival (PFS), and tolerability were assessed. Results: In Study 206 (N=56), 48% and 46% received prior A and T, and in Study 208 (N=52), 21% and 44% received prior A and T, respectively. Objective response rates (ORRs), the primary endpoint, were similar in pts, regardless of prior A or T tx, except in pts w/o prior T in Study 208 whose ORR trended higher (table). In both studies, clinical benefit rate (CBR), PFS, and duration of response (DOR) were either similar or trended higher in pts w/o prior A or T. PFS was higher in HER2+ pts receiving eribulin + TRAS who had not received prior A or T compared with those who had. Grade (G) 3-5 AE rates were similar or lower in pts who had not received prior A or T. Conclusions: As first-line therapy, eribulin in HER2- pts and eribulin + TRAS in HER2+ pts were effective and well tolerated, regardless of prior A or T tx. However, in HER2+ pts receiving eribulin + TRAS, the lack of prior A or T tx may be a predictor of longer median PFS. Clinical trial information: NCT01268150 and NCT01269346.