Clinic Conversation of the Week: How to Talk to Patients About Imlunestrant for Advanced Breast Cancer

What is Imlunestrant?

Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen receptor degrader (SERD) that inhibits continuous estrogen receptor (ER), including in cancers with mutations in the ESR1 gene, which encodes ERα. ESR1 mutations are known to drive resistance to standard endocrine therapies in ER-positive and human epidermal growth factor receptor (HER2)–negative breast cancer. By directly targeting and degrading the ER, imlunestrant offers a novel therapeutic approach for patients whose disease has progressed following prior endocrine treatments.

Evidence Supporting Imlunestrant Use

The efficacy and safety of imlunestrant have been evaluated in EMBER-3 (NCT04975308), a phase 3, open-label trial. The trial enrolled patients with ER-positive, HER2-negative advanced breast cancer that had recurred or progressed during or after aromatase inhibitor therapy, either alone or in combination with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.

Patients were randomized 1:1:1 to receive imlunestrant monotherapy, standard-of-care (SOC) endocrine therapy, or imlunestrant in combination with abemaciclib. The primary end points focused on progression-free survival (PFS), particularly among patients with ESR1 mutations and the overall population. A total of 874 patients participated, with 331 receiving imlunestrant monotherapy, 330 undergoing SOC endocrine therapy, and 213 receiving the imlunestrant plus abemaciclib combination.

Key Findings From EMBER-3

Results of the trial were presented at the San Antonio Breast Cancer Symposium (SABCS) this December.

• ESR1-mutated population:
  • Median PFS with imlunestrant was 5.5 months, compared to 3.8 months with SOC endocrine therapy (hazard ratio , 0.62; P<0.001)
  • The restricted mean survival time at 19.4 months was 7.9 months with imlunestrant versus 5.4 months with SOC
• Overall population:
  • The median PFS was 5.6 months with imlunestrant and 5.5 months with SOC therapy (HR, 0.87; P=0.12)
• Combination Therapy (Imlunestrant + Abemaciclib):
  • In the overall population, the combination therapy achieved a median PFS of 9.4 months compared to 5.5 months for imlunestrant monotherapy (HR, 0.57; P<0.001)

Safety Profile

• Grade 3 or higher adverse events occurred in 17.1% of patients receiving imlunestrant, 20.7% with SOC therapy, and 48.6% with the combination therapy
• The combination therapy’s safety profile was consistent with known adverse effects of abemaciclib, with no new safety signals reported

What These Results Mean

• Imlunestrant significantly improved PFS in patients with ESR1 mutations compared to standard therapy
• The combination of imlunestrant and abemaciclib enhanced PFS across the overall population, regardless of ESR1 mutation status
• The safety profile aligns with expectations, reinforcing the potential for imlunestrant as an effective therapeutic option post-endocrine therapy progression

Imlunestrant, alone or in combination, represents a promising advance in the treatment of ER-positive, HER2-negative advanced breast cancer, particularly for patients harboring ESR1 mutations.

What should we tell patients about this research?

Here’s What I Would Say

Imlunestrant is an oral medication designed to treat advanced breast cancer that is ER-positive and HER2-negative. It works by targeting and breaking down estrogen receptors, which fuel the growth of some breast cancers. This treatment is especially helpful for patients whose cancer has developed resistance to other endocrine therapies.

In clinical trials, imlunestrant showed the most benefit in patients with a specific mutation, ESR1, which is linked to treatment resistance. For those patients, imlunestrant delayed cancer progression longer than standard treatments. When combined with another drug, abemaciclib, the combination further improved outcomes for a broader group of patients.

If you have ER-positive, HER2-negative breast cancer and your disease has progressed despite previous treatments, imlunestrant might be a suitable option. Your oncologist can discuss whether imlunestrant or a combination therapy could be part of your treatment plan based on your cancer’s characteristics.

For More Information

Jhaveri KL, Neven P, Casalnuovo ML, et al (2024). Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and combined with abemaciclib, for patients with ER+, HER2- advanced breast cancer (ABC), pretreated with endocrine therapy (ET): results of the phase 3 EMBER-3 trial. Presented at: 2024 San Antonio Breast Cancer Symposium. Abstract GS1-01.

Jhaveri KL, Neven P, Casalnuovo ML, et al (2024). Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. DOI:10.1056/NEJMoa2410858

About Dr. Hundal

Jasmin Hundal, MD, MS, MPH, is a second-year Hematology/Oncology Fellow at the Cleveland Clinic in Cleveland, Ohio. Previously, she completed her Internal Medicine Residency at the University of Connecticut. Dr. Hundal’s main area of interest is the overlap between cardiometabolic health and cancer, particularly for breast cancer patients and survivors. Outside of work, she enjoys traveling, cooking, and hiking.