Inluriyo, an oral therapy for ER+, HER2– metastatic breast cancer with ESR1 mutations, offers a new treatment option after prior endocrine therapy.
The U.S. Food and Drug Administration (FDA) has approved Inluriyo (imlunestrant, 200 mg tablets) for the treatment of adults with estrogen receptor (ER)-positive and HER2-negative breast cancer.
The regulatory approval of the oral estrogen receptor antagonist is for patients whose cancer has an ESR1 mutation and has advanced or spread (also known as metastatic breast cancer). Additionally, the designation is meant for people whose disease worsened after receiving at least one prior line of endocrine therapy.
"This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches," Jacob Van Naarden, executive vice president and president of Lilly Oncology, said in the news release. "We are deeply grateful to the patients, investigators, Lilly team members and clinical care teams who made this advancement possible. This therapy has the potential to make the treatment journey more manageable for those living with breast cancer."
The FDA approved Inluriyo based on the results of the EMBER-3 trial which evaluated 256 patients with ESR1-mutated metastatic breast cancer. In the study, patients received Inluriyo or endocrine therapy as first-line treatment after their cancer returned following adjuvant aromatase inhibitor (AI) therapy, with or without a prior CDK4/6 inhibitor (21% of patients). Others received Inluriyo or endocrine therapy as second-line treatment after disease progression on aromatase inhibitor, with or without a prior CDK4/6 inhibitor (79% of patients).
Inluriyo lowered the risk of cancer progression or death by 38% compared with standard endocrine therapy. For patients with ESR1-mutated metastatic breast cancer, Inluriyo significantly improved progression-free survival compared with Faslodex (fulvestrant) and Aromasin (exemestane). The median progression-free survival was 5.5 months with Inluriyo versus 3.8 months with standard therapy.
Risk of progression or death: measure of how much treatment changes the chance of cancer worsening or death over time.
Progression-free survival (PFS): time during and after treatment in which the disease does not worsen.
Median progression-free survival (median PFS): the middle point where half of patients have not experienced disease progression.
Inluriyo treats ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer. Some breast cancers develop ESR1 mutations that can make estrogen receptors overactive, driving cancer growth. Inluriyo works by binding to these receptors, blocking them, and helping break them down, which can slow the cancer’s progression. Its once-daily oral dosing gives patients a convenient treatment option.
In EMBER-3, most side effects of Inluriyo were mild to moderate. The most common side effects (10% or more of patients), including lab changes, were low hemoglobin, muscle or joint pain, low calcium, low neutrophils, increased liver enzymes (AST and ALT), fatigue, diarrhea, increased triglycerides, nausea, low platelets, constipation, increased cholesterol, and abdominal pain. In the study, 4.6% of patients stopped treatment permanently due to side effects. Dose reductions and interruptions happened in 2.4% and 10% of patients, respectively.
Inluriyo is also being studied in the ongoing phase 3 EMBER-4 trial for people with ER-positive, HER2-negative early breast cancer at higher risk of recurrence. This study is enrolling about 8,000 patients worldwide.
"The approval of Inluriyo expands the metastatic breast cancer treatment landscape for patients who test positive for the ESR1mutation," Jean Sachs, CEO, Living Beyond Breast Cancer, said in the news release. "Eligible patients will now have access to an additional treatment option, offering them the potential for flexibility in their daily lives and disease management, and — above all — renewed hope for the future."
EMBER-3 is a Phase 3, randomized, open-label study in adults with ER-positive, HER2-negative locally advanced or metastatic breast cancer whose disease returned or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor. The trial enrolled 874 patients, with 32% entering from the adjuvant setting and 64% as second-line treatment after progression on prior therapy. Participants were randomly assigned to Inluriyo, Faslodex or Aromasin, or Inluriyo plus Verzenio (abemaciclib). More information about the EMBER-3 study is available on clinicaltrials.gov.
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