Lilly's Imlunestrant Boosts Progression-Free Survival in ER+, HER2- Breast Cancer

Eli Lilly and Company has unveiled promising results from its Phase 3 EMBER-3 trial involving imlunestrant, a novel oral selective estrogen receptor degrader (SERD). This trial, which focused on patients with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, highlighted significant advancements in treatment options. The study involved patients whose cancer had progressed after prior treatment with an aromatase inhibitor (AI), with or without a CDK4/6 inhibitor.

The findings were presented at the 2024 San Antonio Breast Cancer Symposium and published in the New England Journal of Medicine. Imlunestrant, as a standalone treatment, demonstrated a substantial 38% reduction in the risk of disease progression or death compared to standard endocrine therapy in patients with ESR1 mutations. Furthermore, when combined with Verzenio (abemaciclib), a CDK4/6 inhibitor, imlunestrant reduced the risk of progression or death by 43% compared to imlunestrant alone, irrespective of ESR1 mutation status.

Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center, a principal investigator of the study, emphasized the significance of these results, noting that the median progression-free survival observed in the EMBER-3 trial is one of the most encouraging seen in CDK4/6 pre-treated ER+, HER2- advanced breast cancer patients. This suggests a potential shift in available treatment options for this patient group, which is currently limited.

The EMBER-3 trial enrolled 874 patients who were randomized into three groups: those receiving imlunestrant alone, standard of care endocrine therapy, and a combination of imlunestrant with abemaciclib. The study's primary endpoints focused on progression-free survival rates among patients with ESR1 mutations and the overall patient population. The trial demonstrated that imlunestrant alone had a statistically significant improvement in progression-free survival for patients with ESR1 mutations, with a median progression-free survival of 5.5 months compared to 3.8 months in standard therapy.

In addition to improving progression-free survival, the combination of imlunestrant and abemaciclib showed a consistent improvement across various subgroups, regardless of mutation status or prior CDK4/6 inhibitor treatment. The safety profile of the combination therapy was in line with known side effects of fulvestrant with abemaciclib, such as low-grade diarrhea, nausea, and neutropenia, with a low treatment discontinuation rate.

Overall survival results from the EMBER-3 study are not yet mature, as continued data collection is ongoing. Dr. David Hyman, Chief Medical Officer at Lilly, remarked on the groundbreaking nature of combining an oral SERD with a CDK4/6 inhibitor, which could provide a valuable all-oral treatment option for patients.

Breast cancer remains a significant health challenge worldwide, with ER+ breast cancer being a common type. Following progression on initial therapies, patients often receive treatments like fulvestrant, which requires intramuscular injections. The development of imlunestrant as an oral treatment option offers convenience and continuous estrogen receptor target inhibition, presenting a new horizon for patient management.

The EMBER-3 results hold promise for the future of breast cancer therapy, with submission plans to regulatory authorities underway. Additionally, imlunestrant is being investigated in the adjuvant setting for early-stage breast cancer with an increased risk of recurrence in the ongoing EMBER-4 trial. This global study aims to enroll 6,000 patients, further exploring the potential of imlunestrant in breast cancer treatment.