Lilly's Imlunestrant, an Oral SERD, Significantly Improved Progression-Free Survival as Monotherapy and in Combination with Verzenio® (abemaciclib) in Patients with ER+, HER2- Advanced Breast Cancer

Clinical Trial Results - Imlunestrant as monotherapy significantly reduced the risk of progression or death by 38% compared to standard endocrine therapy (ET) in patients with ESR1 mutations [1] - Imlunestrant in combination with Verzenio reduced the risk of progression or death by 43% compared to imlunestrant alone, regardless of ESR1 mutation status [1] - Median progression-free survival (PFS) was 5.5 months with imlunestrant versus 3.8 months with standard of care ET in patients with ESR1 mutations [4] - Median PFS for imlunestrant-abemaciclib combination was 9.4 months versus 5.5 months for imlunestrant alone in all patients [6] - Overall response rate (ORR) was 27% for imlunestrant-abemaciclib versus 12% for imlunestrant alone [7] Study Design and Patient Population - EMBER-3 is a Phase 3, randomized, open-label study of imlunestrant, investigator's choice of endocrine therapy, and imlunestrant in combination with abemaciclib [11] - The trial enrolled 874 adult patients with ER+, HER2- locally advanced or metastatic breast cancer [11] - 32% of patients enrolled as first-line treatment for advanced breast cancer (ABC), and 64% as second-line treatment following progression on initial therapy [11] - Randomization was stratified by prior CDK4/6 inhibitor use, presence of visceral metastases, and geographic region [3] Safety and Tolerability - Safety profile of imlunestrant-abemaciclib was consistent with known safety profile of fulvestrant in combination with abemaciclib [8] - Most common adverse events included diarrhea (86%), nausea (49%), neutropenia (48%), and anemia (44%) [8] - Discontinuation rate due to adverse events was low at 6.3% [8] Market and Industry Context - Imlunestrant is an orally administered, brain penetrant, pure ER antagonist that delivers continuous ER target inhibition [9] - Current standard treatment for ER+ breast cancer after progression on initial endocrine therapy is fulvestrant, which is administered via intramuscular injection [9] - 72% of patients receiving fulvestrant reported injection site pain, swelling, or redness, highlighting the need for oral alternatives [9] - Imlunestrant is also being investigated in the adjuvant setting for ER+, HER2- early breast cancer (EBC) with an increased risk of recurrence [10] Breast Cancer Epidemiology - Breast cancer is the second most commonly diagnosed cancer worldwide, with an estimated 2.3 million new cases in 2022 [13] - In the US, it is estimated that there will be more than 310,000 new cases of breast cancer diagnosed in 2024 [13] - Approximately 30% of high-risk early-stage breast cancer cases in the US will become metastatic [12] - Five-year relative survival rates are 99% for localized disease, 86% for regional/locally advanced disease, and 30% for metastatic/advanced disease [12]