FDA Approves Imlunestrant for ER+ and HER2-Negative Breast Cancer

The FDA approved imlunestrant (Inluriyo; Eli Lilly and Company) for treating adults with various subtypes of breast cancer.¹

The oral estrogen receptor (ER) degrader is used to treat adults with ER-positive, HER2-negative, ESR1-mutated advanced, or metastatic breast cancer (MBC) whose disease continued to progress even after 1 line of endocrine therapy (ET). The phase 3 EMBER trial (NCT 04975308) that the approval was based on was shown in improver progression-free survival (PFS) when used adjunctively with the kinase inhibitor abemaciclib (Verzenio)—used to treat hormone receptor (HR)–positive and HER2-negative breast cancer. In the open-label trial, patients with ER-positive, HER2-negative breast cancer were randomized in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. The mean PFS for the imlunestrant-abemiciclib group was 9.4 months when compared with the imlunestrant group at 5.5 months, still significantly greater than that of the standard endocrine monotherapy group, whose PFS was 3.8 months.²

Whereas ER-positive and HER2-negative breast cancers are the most common subtypes of breast cancer, some cancers can develop ESR1 mutations that can cause estrogen to become overactive and fuel cancer growth.

Fulvestrant is currently the only drug approved for both mono- and combination therapy; however, its inability to be administered orally limited it to intramuscular administration. Thus, limiting its dose and therefore dose-dependent efficacy, in addition to the administration often being painful for patients and requiring in-office administration.² As an oral ER degrader, imlunestrant’s efficacy and administration have not only improved but also have the potential to remove social barriers to access while it is still being studied for combination therapy use with abemaciclib fro advacned breast cancer.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. "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."¹

The adverse events (AEs) reported in the study were experienced by more patients in the imlunestrant-abemiciclib group when compared with the imlunestrant and standard ET group. In the safety population there were 327 patients in the imlunestrant group, 324 in the standard ET group, and 208 in the imlunestrant-abemiciclib group.

The most common AEs in the imlunestrant and standard ET groups were fatigue (22.6% vs 13.3% of the patients), diarrhea (21.4% vs 11.7%), and nausea (17.1% vs 13.0%). Furthermore, AEs of a grade 3 or higher occurred in 17.1% of the imlunestrant group and in 20.7% of the standard ET group—which consisted of anemia (2.1% vs 2.8%) and neutropenia (2.1% vs 1.9%).

In contrast, the most common AEs in the imlunestrant-abemiciclib group were diarrhea (86.1%), nausea (48.6%), neutropenia (48.1%), and anemia (43.8%). AEs of a grade 3 or higher occurred in 48.6% of patients—consisting primarily of neutropenia (19.7%), diarrhea (8.2%), and anemia (7.7%)

"This represents an important advancement for patients with ESR1-mutated MBC, a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance," said Komal Jhaveri, MD, section head of Endocrine Therapy Research and clinical director of Early Drug Development at Memorial Sloan Kettering Cancer Center, and a principal investigator of EMBER-3. "With its demonstrated efficacy, tolerability profile, and oral administration, this therapy provides a meaningful alternative treatment option for this patient population."

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://investor.lilly.com/news-releases/news-release-details/us-fda-approves-inluriyo-imlunestrant-adults-er-her2-esr1

2. Jhaver KL, Neven P, Casalnuovo, et al. Imlunestrant with or without abemaciclib in advanced breast cancer. N Engl J Med. 2025;392:1189-1202. doi:10.1056/NEJMoa2410858