Eli Lilly achieves breakthrough with Imlunestrant in Phase 3 breast cancer trial

Eli Lilly and Company has announced encouraging results from its Phase 3 EMBER-3 study evaluating imlunestrant, an investigational oral selective estrogen receptor degrader (SERD), for advanced breast cancer treatment. The trial focused on patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) that progressed after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor. This milestone highlights the growing importance of targeted therapies in managing advanced breast cancer, a field where treatment options remain limited for many patients.

The study revealed that imlunestrant significantly improved progression-free survival (PFS) compared to standard endocrine therapy (SOC ET) in patients with an ESR1 mutation, reducing the risk of progression or death by 38%. Moreover, when combined with Verzenio (abemaciclib), imlunestrant demonstrated an even greater benefit, reducing this risk by 43% across all patient groups. These findings underscore the potential of combining novel SERDs with established CDK4/6 inhibitors to improve outcomes for patients with advanced disease.

Promising Data from EMBER-3

The EMBER-3 trial enrolled 874 adult patients, with participants receiving either imlunestrant monotherapy, SOC ET such as fulvestrant or exemestane, or a combination of imlunestrant with abemaciclib. The trial included patients treated both in first-line and second-line settings following progression on initial endocrine therapy for advanced breast cancer. The diversity of patient groups included ensures that the findings have broad applicability, providing critical insights for a range of clinical scenarios.

Patients with an ESR1 mutation receiving imlunestrant experienced a median progression-free survival of 5.5 months compared to 3.8 months with SOC ET. This significant improvement highlights imlunestrant’s potential to address endocrine therapy resistance, a common hurdle in managing advanced breast cancer. Among all patients, the combination of imlunestrant and abemaciclib yielded a median progression-free survival of 9.4 months, outperforming imlunestrant monotherapy, which had a median PFS of 5.5 months. These results reflect a promising shift towards more effective treatment combinations that leverage the strengths of multiple targeted therapies.

A New Therapeutic Option

Imlunestrant is designed to deliver continuous estrogen receptor (ER) inhibition, even in cancers with ESR1 mutations, and is brain-penetrant, potentially addressing central nervous system metastases. The drug’s oral SERD therapy formulation offers a more convenient alternative to fulvestrant, a widely used therapy administered via intramuscular injection. For many patients, transitioning to an oral SERD therapy could mean fewer hospital visits and improved quality of life while maintaining effective disease management.

Dr. Komal Jhaveri, a principal investigator from Memorial Sloan Kettering Cancer Center, highlighted the combination of imlunestrant and abemaciclib as a potentially transformative all-oral regimen for estrogen receptor-positive advanced breast cancer. The treatment’s safety profile was consistent with existing therapies, with manageable side effects like diarrhea, neutropenia, and nausea. This combination represents an important step forward in creating accessible and patient-friendly treatment options for advanced breast cancer.

Beyond its role in addressing metastatic disease, imlunestrant is also being investigated in the adjuvant setting. Early results suggest it could play a significant role in preventing recurrence in patients with high-risk early-stage breast cancer. This expansion into early breast cancer treatment may further solidify imlunestrant’s position as a versatile and impactful therapy across the spectrum of ER+ breast cancers.

Looking Ahead

While overall survival data remain immature, EMBER-3 is the first Phase 3 study to demonstrate the benefits of combining an oral SERD therapy with a CDK4/6 inhibitor. These findings could significantly impact the treatment landscape for advanced breast cancer, especially for patients facing endocrine therapy resistance. The study sets the stage for further investigation in early breast cancer through the Phase 3 EMBER-4 trial, which aims to recruit 6,000 patients globally. The ability to extend such benefits to early breast cancer patients could herald a new era in comprehensive breast cancer care.

Eli Lilly intends to submit the data for regulatory review worldwide, a move that could make imlunestrant a pivotal therapy for patients who have limited options following progression on standard endocrine therapy. Regulatory submissions, coupled with planned expansions into additional trials, indicate a robust pipeline aimed at maximizing the impact of imlunestrant in oncology.

The broader oncology community is already taking note of these advancements, as evidenced by the publication of EMBER-3’s results in The New England Journal of Medicine and its presentation at the San Antonio Breast Cancer Symposium. The inclusion of imlunestrant in key discussions among leading oncologists reflects its growing relevance and potential to reshape treatment standards for advanced breast cancer.