New Oral SERD Approved for Certain Estrogen Receptor-mutated Breast Cancers
The FDA has approved imlunestrant for certain patients with advanced ESR1-mutated breast cancer that has progressed following previous endocrine therapy.
The U.S. Food and Drug Administration (FDA) has approved imlunestrant (Inluriyo) for the treatment of adult patients with advanced or metastatic breast cancer that expresses the estrogen receptor (ER), does not overexpress human epidermal growth factor receptor 2 (HER2), possesses mutations in the estrogen receptor-1 (ESR1) gene, and has progressed after at least one line of endocrine therapy.
The FDA also approved the Guardant360 CDx assay as a companion diagnostic to detect ESR1 gene mutations in patients’ breast tumors in order to determine their eligibility for treatment with imlunestrant.
Imlunestrant is a type of endocrine therapy known as a selective estrogen receptor degrader (SERD) that blocks the activity of ER, destabilizes it, and promotes its degradation in order to disrupt ER’s ability to drive the development and progression of breast cancer. Imlunestrant is the third SERD to be approved by the FDA, following fulvestrant (Faslodex) and elacestrant (Orserdu), the first SERD available as a pill. In contrast to fulvestrant, imlunestrant, which is also taken orally, has the ability to cross the blood-brain barrier, and thus may be effective against breast cancer metastases in the brain.
Among the 256 patients with ESR1-mutated breast cancer, 14.3% of patients treated with imlunestrant alone experienced a response compared with 7.7% of those treated with fulvestrant or exemestane. Furthermore, half of the patients treated with imlunestrant monotherapy experienced at least 5.5 months before disease progression, compared with 3.8 months in those treated in the investigator’s choice group. This corresponded to a 38% reduction in the risk of progression in patients treated with imlunestrant alone compared with those who received either fulvestrant or exemestane. Results from this trial were presented at the 2024 San Antonio Breast Cancer Symposium (SABCS) and featured in an AACR blog post and press release.
The recommended dose for imlunestrant is 400 mg orally once per day, on an empty stomach at least two hours before food, or one hour after food, until disease progression or unacceptable toxicity.
According to federal statistics, it was estimated that 316,950 individuals would be diagnosed with breast cancer and approximately 42,170 patients would die of the disease in the United States in 2025. Approximately 70% of breast cancer cases are hormone receptor-positive and HER2-negative.
The FDA rendered its decision on September 25, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.