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

Imlunestrant with or without Abemaciclib in Advanced Breast Cancer (ABC): a Subgroup Analysis in CDK4/6 inhibitor (CDK4/6i)-pretreated patients from EMBER-3 (126747)

Cristina Saura 1 , Lisa A Carey 2 , Giuseppe Curigliano 3 4 , Nadia Harbeck 5 6 , Joyce O'Shaughnessy 7 , François-Clément Bidard 8 , Monica Lis Casalnuovo 9 , Sung-Bae Kim 10 , Eriko Tokunaga 11 , Norikazu Masuda 12 , Junichiro Watanabe 13 , Xiaojia Wang 14 , Quchang Ouyang 15 , Hee Kyung Ahn 16 , Christoph Cramer von Laue 17 , Shanshan Cao 17 , Holly Knoderer 17 , Komal L Jhaveri 18 19 , Philippe Aftimos 20 , Dion Marinkovich 21
  1. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain
  2. University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
  3. University of Milano, Milano, Italy
  4. Italy and European Institute of Oncology, IRCCS, Milano, Italy
  5. Breast Center, Department of Obstetrics and Gynecology and Comprehensive Cancer Center Munich, Munich, Germany
  6. Ludwig Maximilians University Munich University Hospital, Munich, Germany
  7. Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, Texas, USA
  8. Institut Curie and University of Versailles Saint-Quentin-en-Yvelines-Paris-Saclay University, Paris, France
  9. Hospital María Curie, Buenos Aires, Argentina
  10. Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of South Korea
  11. National Hospital Organization (NHO) Kyushu Cancer Center, Fukuoka, Japan
  12. National Hospital Organization Osaka National Hospital, Osaka, Japan
  13. Juntendo University Graduate School of Medicine, Tokyo, Japan
  14. Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
  15. Breast Internal Medicine Department, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
  16. Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of South Korea
  17. Eli Lilly and Company, Indianapolis, Indiana, USA
  18. Memorial Sloan Kettering Cancer Center , New York, USA
  19. Weill Cornell Medical College , New York, USA
  20. Institut Jules Bordet Hôpital Universitaire de Bruxelles, Brussels, Belgium
  21. Eli Lilly Australia, Sydney, Australia

Imlunestrant is a next-generation, brain-penetrant, oral SERD. The EMBER-3 trial reported significant PFS improvement with imlunestrant over standard therapy (SOC; fulvestrant or exemestane) in patients with ESR1-mutations (m), and with imlunestrant+abemaciclib over imlunestrant in all patients, regardless of ESR1m. There remains a need for effective and tolerable treatments available to a broad unselected population, after disease progression on CDK4/6i. Abemaciclib+fulvestrant has shown benefit over fulvestrant in this context (postMONARCH trial). Here we present a subgroup analysis of imlunestrant+abemaciclib vs imlunestrant in patients with disease progression on CDK4/6i.

874 patients with ER+, HER2- ABC and progression on/after aromatase inhibitor ± CDK4/6i were randomized 1:1:1 to imlunestrant, SOC or imlunestrant+abemaciclib. Randomization was stratified by prior CDK4/6i treatment, presence of visceral metastases, and region. Subgroup analyses of PFS by clinico-genomic factors were performed for imlunestrant+abemaciclib vs imlunestrant in patients with prior CDK4/6i treatment.

Of 874 total patients, 426 were concurrently randomized to imlunestrant+abemaciclib or imlunestrant (n=213 each); the majority (n= 279, 65%) had received prior CDK4/6i. Among CDK4/6i-pretreated patients baseline characteristics were generally balanced; 56% had visceral metastases, 37% had ESR1m and 40% had PI3K-pathway mutations. Most patients (70%) had received prior CDK4/6i for ≥12 months. PFS benefit of imlunestrant+abemaciclib over imlunestrant (HR=0.51 [95%CI:0.38-0.68]; mPFS 9.1vs3.7 months) showed broadly consistent effect across key clinico-genomic subgroups: ESR1m (HR=0.44 [95%CI:0.28-0.70]; PI3K-pathway mutation (HR=0.52 [95%CI:0.34-0.79); Concurrent ESR1m/PI3K-pathway mutation (HR=0.32 [95%CI:0.16-0.63). Benefit was observed regardless of prior CDK4/6i duration or type, though analyses of prior abema patients were limited by a small sample size.

In patients with ER+, HER2- ABC who have progressed on prior CDK4/6i, imlunestrant+abemaciclib showed a consistent benefit over imlunestrant, regardless of clinico-genomic factors. EMBER-3 is the 1st phase 3 trial to show benefit of an oral SERD+CDK4/6i after disease progression on prior CDK4/6i.