220P Elacestrant vs fulvestrant or aromatase inhibitor (AI) in phase III trial evaluating elacestrant, an oral selective estrogen receptor degrader (SERD), vs standard of care (SOC) endocrine monotherapy for ER+/HER2- advanced/metastatic breast cancer (mBC): Subgroup analysis from EMERALD

The EMERALD clinical trial showed significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for elacestrant vs SOC endocrine therapy in patients (pts) with ER+/HER2- mBC following progression on prior endocrine and CDK4/6 inhibitor therapy. Benefit was observed in the overall population and in pts with ESR1 mutations (mESR1). Here, we report a subgroup analysis from EMERALD comparing efficacy with elacestrant to fulvestrant or AI. EMERALD (NCT03778931) is a randomized, open-label, phase 3 trial that enrolled pts with ER+/HER2− mBC who had 1–2 lines of endocrine therapy, mandatory pretreatment with a CDK4/6i, and ≤1 chemotherapy. Pts were randomized 1:1 to elacestrant (400 mg orally daily) or SOC choice of fulvestrant or AI; the protocol recommended that pts previously treated with fulvestrant receive AI, and pts previously treated with AI receive fulvestrant. Primary endpoints were PFS in all pts and in pts with mESR1. This post-hoc analysis compared PFS in elacestrant vs fulvestrant and vs AI groups. Among the 477 pts enrolled in the trial, n=239 received elacestrant, n=165 received fulvestrant (all pretreated with AI except n=6), and n=73 received AI (all pretreated with fulvestrant except n=4). Treatment with elacestrant was associated with prolonged PFS at 6, 12, 15, and 18 months compared to fulvestrant or AI in both the overall population and pts with mESR1 (Table). The safety profile was manageable. The most common adverse event observed with elacestrant was nausea (all grade: 35.0% [vs 16.1% fulvestrant, 25.0% AI]; grade 3/4: 2.5% [vs 0% fulvestrant, 2.9% AI]). Among pts with ER+/HER2− mBC, elacestrant prolonged PFS compared to both fulvestrant as well as AI, highlighting superior efficacy regardless of type of endocrine therapy.Table: 220PAllESR1 mutElacestrant (n=239)Fulvestrant (n=165)AI(n=73)Elacestrant(n=115)Fulvestrant(n=83)AI(n=30)HR for PFS (95% CI)Ref0.68 (0.52-0.90)0.78 (0.52-1.17)Ref0.50 (0.34-0.74)0.66 (0.32-1.33)PFS rate, % (95% CI)6 mo34.3 (27.1-41.5)22.9 (15.2-30.6)13.4 (3.1-23.6)40.8 (30.1-51.4)20.8 (10.7-30.8)12.3 (0-27.8)12 mo22.3 (15.2-29.4)10.2 (3.4-16.9)6.7 (0-15.0)26.8 (16.2-37.4)8.4 (0.2-1.7)NE15 mo19.2 (11.9-26.6)10.2 (3.4-16.9)6.7 (0-15.0)24.3 (13.7-35.0)NENE18 mo16.8 (9.0-24.6)NENE24.3 (13.7-35.0)NENENE, not estimable; Ref, reference. Open table in a new tab