FDA Approves Imlunestrant in ER+, ESR1-Mutant Breast Cancer

The US FDA has approved imlunestrant (Inluriyo) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2–, ESR1-mutated advanced or metastatic breast cancer whose disease has progressed after at least 1 line of endocrine therapy.^1,2

"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," said Jacob Van Naarden, executive vice president and president of Lilly Oncology, in a press release.¹ "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."

Data from the phase 3 EMBER-3 trial (NCT04975308) support this approval and were presented at the 2024 San Antonio Breast Cancer Symposium.³ In the trial, imlunestrant reduced the risk of disease progression or death by 38% vs endocrine therapy. Findings showed that patients with ESR1-mutated disease treated with imlunestrant monotherapy (n = 138) experienced a median progression-free survival (PFS) of 5.5 months (95% CI, 3.9–7.4) compared with 3.8 months (95% CI, 3.7–5.5) for those given standard-of-care endocrine therapy of fulvestrant or exemestane (n = 118; HR, 0.62; 95% CI, 0.46-0.82; P <.001).

In the overall population, the median PFS was 5.6 months (95% CI, 5.3–7.3) for imlunestrant monotherapy (n = 331) vs 5.5 months (95% CI, 4.6–5.6) for endocrine therapy (n = 330; HR, 0.87; 95% CI, 0.72–1.04; P =.12). Notably, there was no statistical difference in PFS between the 2 arms for patients without ESR1 mutations (HR, 1.00; 95% CI, 0.79–1.27).

Among patients with measurable disease, the investigator-assessed overall response rate (ORR) was 12% (95% CI, 8%–16%) for imlunestrant (n = 262) vs 8% (95% CI, 5%–12%) for endocrine therapy (n = 251) in the overall population. The ORR was 14% (95% CI, 8%–21%) for imlunestrant alone (n = 112) vs 8% (95% CI, 2%–13%) for endocrine therapy (n = 91) in the ESR1-mutated population; the respective ORRs were 11% (95% CI, 6%–16%) and 9% (95% CI, 4%–13%) for imlunestrant (n = 150) and endocrine therapy (n = 160) in the population of patients without ESR1 mutations.

Safety data showed that any-grade treatment-emergent adverse events (TEAEs) occurred in 83% of patients in the imlunestrant monotherapy arm (n = 327) vs 84% of patients in the endocrine therapy arm (n = 334). The rates of grade 3 or higher TEAEs were 17% and 21%, respectively. The most common any-grade TEAEs reported in at least 10% of patients included fatigue (imlunestrant, 23%; endocrine therapy, 13%), diarrhea (21%; 12%), nausea (17%; 13%), arthralgia (14%; 14%), increased aspartate aminotransferase levels (13%; 13%), back pain (11%; 7%), increased alanine aminotransferase levels (10%; 10%), anemia (10%; 13%), and constipation (10%; 6%).

Serious AEs occurred in 10% of patients in the imlunestrant arm vs 12% of patients in the endocrine therapy arm. In the imlunestrant monotherapy group, AEs led to dose reductions, treatment discontinuation, and death in 2%, 4%, and 2% of patients, respectively. These respective rates were 0%, 1%, and 1% in the endocrine therapy group.

REFERENCES:

1. U.S. FDA approves Inluriyo (imlunestrant) for adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer. News release. Eli Lilly and Company. September 25, 2025. Accessed September 25, 2025. https://tinyurl.com/39fjy4n3

2. FDA approves imlunestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. US FDA. News release. September 25, 2025. Accessed September 25, 2025. https://tinyurl.com/3p5axp5n

3. Jhaveri KL, Neven P, Casalnuovo ML, et al. 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; December 10-14, 2024; Abstract GS1-01.