Abstract 220P
Background
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.
Methods
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.
Results
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]).
Conclusions
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: 220P
| All | ESR1 mut | |||||
| Elacestrant (n=239) | Fulvestrant (n=165) | AI(n=73) | Elacestrant(n=115) | Fulvestrant(n=83) | AI(n=30) | |
| HR for PFS (95% CI) | Ref | 0.68 (0.52-0.90) | 0.78 (0.52-1.17) | Ref | 0.50 (0.34-0.74) | 0.66 (0.32-1.33) |
| PFS rate, % (95% CI) | ||||||
| 6 mo | 34.3 (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 mo | 22.3 (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) | NE |
| 15 mo | 19.2 (11.9-26.6) | 10.2 (3.4-16.9) | 6.7 (0-15.0) | 24.3 (13.7-35.0) | NE | NE |
| 18 mo | 16.8 (9.0-24.6) | NE | NE | 24.3 (13.7-35.0) | NE | NE |
NE, not estimable; Ref, reference.
Clinical trial identification
NCT03778931.
Editorial acknowledgement
Editorial assistance was provided by Mark Phillips, PharmD, and Laura Evans, PharmD, of Phillips Gilmore Oncology Communications, Inc, funded by the Menarini Group.
Legal entity responsible for the study
Menarini Group.
Funding
Menarini Group.
Disclosure
P.G. Aftimos: Financial Interests, Personal, Other, Honoraria: Synthon; Financial Interests, Personal, Other, Honoraria and Advisory Role: Roche, Gilead Sciences; Financial Interests, Personal, Advisory Role: Macrogenics, Boehringer Ingelheim, Novartis, Amcure, Servier, G1 Therapeutics, Radius Health, Deloitte, Menarini; Financial Interests, Personal, Other, Advisory Role,Travel, Accommodations, Expenses: Amgen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology, Roche Belgium, Pfizer. J. Cortés: Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar, Leuko; Financial Interests, Personal, Other, Honoraria: Novartis, Eisai, Celgene, Pfizer, Roche, Samsung, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Celgene, Cellestia Biotech, AstraZeneca, Roche, Seattle Genetics, Daiichi Sankyo, ERYTECH Pharma, Polyphor, Athenex, Lilly, Servier, Merck Sharp & Dohme, GlaxoSmithKline, Leuko, Clovis Oncology. F.C. Bidard: Financial Interests, Personal and Institutional, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Radius Health, Menarini, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, AstraZeneca, Roche, Lilly, Rain Therapeutics; Financial Interests, Institutional, Research Grant, Research Funding: Novartis (Inst), Pfizer (Inst), Menarini Silicon Biosystems (Inst), Prolynx (Inst); Financial Interests, Personal and Institutional, Royalties, Patents, Royalties, Other Intellectual Property: ESR1 & MSI detection techniques (patents; Inst); Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca, Novartis. V. kaklamani: Financial Interests, Personal, Other, Honoraria: Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, daichi, Gilead Sciences; Financial Interests, Personal, Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, Athenex, bioTheranostics; Financial Interests, Personal, Speaker’s Bureau: Genentech, Novartis, Genomic Health, Puma Biotechnology, Pfizer, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Research Grant, Research Funding: Eisai. A. Bardia: Financial Interests, Personal and Institutional, Advisory Role: Novartis, Genentech, Pfizer, Spectrum Pharmaceuticals, bioTheranostics, Merck, Radius Health, Immunomedics (Inst), Novartis (Inst), Genentech/Roche (Inst), Pfizer (Inst), Radius Health (Inst), Innocrin Pharma (Inst), Immunomedics, Sanofi, Puma Biotechnolo; Financial Interests, Institutional, Research Grant, Research Funding: Genentech (Inst), Novartis (Inst), Pfizer (Inst), Merck (Inst), Sanofi (Inst), Radius Health (Inst), Immunomedics (Inst), AstraZeneca/Daiichi Sankyo (Inst). P. Neven: Financial Interests, Institutional, Advisory Role, Travel, Accommodations, Expenses: Lilly, Pfizer, Roche; Financial Interests, Institutional, Advisory Role: Novartis, Radius Health. A. Montero: Financial Interests, Personal, Other, Honoraria: Celgene, AstraZeneca, OncoSec; Financial Interests, Personal, Advisory Role: New Century Health, Welwaze; Non-Financial Interests, Personal, Other, Uncompensated Relationships: Roche. F. Forget: Financial Interests, Other, Travel, Accommodations, Expenses:: Ipsen, Teva. J. Sohn: Financial Interests, Institutional, Research Grant, Research Funding: MSD (Inst), Roche (Inst), Novartis (Inst), Lilly (Inst), Pfizer (Inst), Daiichi Sankyo (Inst), AstraZeneca (Inst), GlaxoSmithKline (Inst), Sanofi (Inst), Boehringer Ingelheim (Inst); Other, Personal, Other, Other Relationships: Roche. D. Taylor: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Personal, Advisory Role: Lilly, AstraZeneca, Roche/Genentech, Novartis, Agendia, MSD, Seattle Genetics; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD, AstraZeneca, Pfizer. K. Harnden: Financial Interests, Personal, Other, Honoraria: E-Health Now; Financial Interests, Personal, Speaker’s Bureau: Eisai, Daiichi Sankyo/AstraZeneca, Seattle Genetics, Merck. H. Khong: Financial Interests, Personal, Stocks/Shares: MEI Pharma, TG Therapeutics, Lipocine, MustangBio, Tiziana Life Sciences, Vaxart, agenus; Financial Interests, Personal, Advisory Role: Celcuity; Financial Interests, Personal, Research Grant, Research Funding: AstraZeneca. P. Dillon: Financial Interests, Institutional, Research Grant, Research Funding: Novartis (Inst), Pfizer (Inst), AbbVie (Inst), Newlink Genetics (Inst), Tesaro (Inst), Merck (Inst), Tolero Pharmaceuticals (Inst), Radius Health (Inst). K.J. Grzegorzewski: Financial Interests, Personal, Other, Employment and Leadership Role: Stemline Therapeutics and Menarini. J. Lu: Financial Interests, Personal, Other, Honoraria: Pfizer, Lilly, Sanofi/Aventis, AstraZeneca/Daiichi Sankyo, Seattle Genetics; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Lilly, Sanofi/Aventis, AstraZeneca/ Daiichi Sankyo; Financial Interests, Institutional, Research Grant, Research Funding: Novartis (Inst), Lilly (Inst), Ambrx (Inst), Genentech (Inst), Radius Health (Inst). All other authors have declared no conflicts of interest.