EMBER-4 is a randomized, unblinded (patients and physicians know the treatment arm at the start of the study) Phase 3 therapy study comparing two endocrine therapies in patients with early estrogen receptor-positive (ER+), HER2-receptor-negative (HER2-) breast cancer who have an increased risk of disease recurrence and who have previously received 2 to 5 years of endocrine therapy after surgery.

What is being investigated in this study?

Breast cancer is diagnosed in most patients at an early stage of the disease. Currently, the standard treatment is surgery followed by endocrine therapy, administered for 5 to 10 years, if the tumor has the following characteristics: early stage, estrogen receptor-positive, and human epidermal growth factor receptor-2-negative (HER2-). If patients have a high risk of recurrence, Abemaciclib (a drug with an inhibitor for a specific protein significantly involved in cell division) can additionally be administered in combination during the first two years. Despite the current standard treatment, a significant proportion of patients experience disease recurrence. Consequently, there is a need to further optimize post-operative treatment and prevent disease recurrence, especially in those patients who have an increased risk of such recurrence. The risk for these patients to develop distant recurrence after 5 years of endocrine therapy depends on the clinico-pathological features at diagnosis, i.e., tumor size, grade, and nodal status.

Imlunestrant belongs to the so-called targeted estrogen receptor degraders. Active substances of this drug class promote the degradation of estrogen receptors on the surface of tumors and thus inhibit their estrogen-dependent growth. Previous studies have indicated that Imlunestrant can specifically stop the cell division of tumor cells, provided the tumor is estrogen receptor-positive.

What is the goal of the study?

The primary goal of this study is to demonstrate that treatment with Imlunestrant has a benefit in efficacy compared to current standard anti-hormone therapy. The study targets patients with an increased risk of disease recurrence, whose tumor is estrogen receptor-positive and HER2-receptor negative, and who have also previously received standard anti-hormone therapy for 2-5 years. Furthermore, the safety and tolerability of the treatments and the quality of life during therapy will be investigated.

How is the study conducted?

Within the study, there are two treatment arms to which patients are randomly assigned in a 1:1 ratio:

Arm 1:
Imlunestrant – oral intake for approx. 5 years

Arm 2:
Tamoxifen or Aromatase Inhibitor (as decided by the treating physicians) – for approx. 5 years

Follow-up for both arms: 5 years

Are there risks?

You will be informed about possible risks or side effects associated with participation during an informational discussion.

Eligibility requirements

Men and women aged 18 and older can participate in this study, with:

• Diagnosis of ER+, HER2 receptor negative, invasive early-stage breast cancer
• Increased risk of disease recurrence
• Resection (surgical removal) without evidence of distant metastases
• Previously completed standard anti-hormone therapy for 2-5 years

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

Where can I participate in this study?
Further information on participating centers can be found here:
https://studienportal-brustkrebs.de/deutschlandkarte

This study is supported by: