Poster Presentation 2025 Joint Meeting of the COSA ASM and IPOS Congress

Imlunestrant with or without Abemaciclib as First- (1L) and Second-line (2L) Therapy in Advanced Breast Cancer (ABC): a Subgroup Analysis from the EMBER-3 trial (126757)

Patrick Neven 1 , Andre Mattar 2 , Antonio Llombart-Cussac 3 , Giuseppe Curigliano 4 5 , Nadia Harbeck 6 7 , Joyce O'Shaughnessy 8 , François-Clément Bidard 9 , Monica Lis Casalnuovo 10 , Sung-Bae Kim 11 , Eriko Tokunaga 12 , Christina Saura 13 , Lisa A Carey 14 , Kamnesh R Pradhan 15 , Shanshan Cao 15 , Monique Coersmeyer 15 , Anna Emde 15 , Francisco Sapunar 15 , Komal L Jhaveri 16 17 , Philippe Aftimos 18 , Dion Marinkovich 19
  1. Multidisciplinary Breast Center, University Hospitals Leuven, Leuven, Belgium
  2. Mastology Department, Women's Health Hospital, São Paulo, Brazil
  3. Oncology Department, Hospital Arnau de Vilanova, Valencia, Spain
  4. University of Milano, Milano, Italy
  5. Italy and European Institute of Oncology, IRCCS, Milano, Italy
  6. Brustzentrum, Frauenklinik and CCC Munich, LMU University Hospital, Munich, Germany
  7. Ludwig Maximilians University Munich University Hospital, Munich, Germany
  8. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas, USA
  9. Institut Curie and University of Versailles Saint-Quentin-en-Yvelines-Paris-Saclay University, Paris, France
  10. Hospital María Curie, Buenos Aires, Argentina
  11. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of South Korea
  12. National Hospital Organization (NHO) Kyushu Cancer Center, Fukuoka, Japan
  13. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
  14. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  15. Eli Lilly and Company, Indianapolis, Indiana, USA
  16. Memorial Sloan Kettering Cancer Center , New York, USA
  17. Weill Cornell Medical College , New York, USA
  18. Institut Jules Bordet Hôpital Universitaire de Bruxelles, Brussels, Belgium
  19. Eli Lilly Australia, Sydney, Australia

Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial in patients with ER+, HER2- ABC and disease progression on/after an aromatase inhibitor (AI) therapy ± CDK4/6 inhibitor (CDK4/6i) showed significant PFS improvement with imlunestrant over standard therapy (SOC) among patients with ESR1 mutations (ESR1m), and with imlunestrant+abemaciclib over imlunestrant in all patients regardless of ESR1m status. An exploratory analysis of efficacy by line-of-therapy is presented here.
Subgroup analyses of PFS were performed by line-of-therapy for imlunestrant (400mg once daily) vs SOC (fulvestrant/exemestane per label) in patients with ESR1m, and imlunestrant (400mg once daily) + abemaciclib (150mg BID) vs imlunestrant and vs SOC in all concurrently randomized patients. Eligible patients included 1L patients with ABC who experienced recurrence on/within 12 months from completion of AI±CDK4/6i as (neo)adjuvant treatment, and 2L patients who progressed on 1L treatment for ABC.
Overall, 33% patients received study therapy as 1L for ABC and 67% as 2L treatment. Among patients with ESR1m across imlunestrant and SOC arms, 21% were treated in the 1L setting (79% 2L). Among all patients, ESR1m were less frequent in 1Lvs2L (24%vs43%), as were incidences of prior CDK4/6i treatment (12%vs83%). Consistent PFS benefit was observed for imlunestrant vs SOC in patients with ESR1m (1L HR=0.48[95%CI:0.25,0.92], 2L HR=0.66[95%CI:0.48,0.90]), and imlunestrant+abemaciclib vs imlunestrant (1L HR=0.55 [95%CI:0.34,0.90], 2L HR=0.62 [95%CI:0.47,0.83]) and vs SOC (1L HR=0.44 [95%CI:0.27,0.71], 2L HR=0.51 [95%CI:0.39,0.68]) in all patients, regardless of line-of-treatment. A numerically longer PFS was observed in 1L patients (imlunestrant+abemaciclib: 14.4 [7.6,NR] vs 9.1 months [7.4,11.1], imlunestrant: 11.1 [4.7,11.1] vs 5.5 months [3.7,5.7], SOC: 5.7 [3.7,8.7] vs 3.8 months [3.7,5.5]).
Consistent with the primary EMBER-3 analyses, a benefit in PFS was observed across 1L and 2L subgroups. Imlunestrant alone or with abemaciclib, provides an all-oral targeted therapy option in the 1L or 2L setting for patients with endocrine therapy-resistant ER+, HER2- ABC.