Imlunestrant — Drug Monograph

Brand names: Inluriyo

Drug class: Hormonal Agent

Mechanism of Action

Oral selective estrogen receptor degrader (SERD). Binds to estrogen receptor alpha (ERα) and induces a unique conformational change that targets the receptor for ubiquitin-proteasomal degradation — completely eliminating ERα protein from breast cancer cells. Critically active against ESR1-activating mutations (D538G, Y537S, Y537N, Y537C), which are the primary mechanism of acquired endocrine resistance found in 30–40% of patients progressing on aromatase inhibitors. Oral bioavailability eliminates the need for intramuscular fulvestrant injections.

FDA Indications

• ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer in adults who received at least one prior line of endocrine-based therapy — as monotherapy (approved September 25, 2025, based on EMBER-3)

Common Side Effects

• Hot flashes / vasomotor symptoms (34%)
• Fatigue (27%)
• Nausea (25%)
• Arthralgia / myalgia (21%)
• Hypercholesterolemia (19%)
• Decreased appetite (15%)
• Diarrhea (14%)
• Headache (13%)
• Bone pain (12%)

Clinical Pearl

Imlunestrant fills the oral-SERD gap in the post-CDK4/6 inhibitor HR+/HER2− setting. EMBER-3 showed PFS benefit in the overall population (HR 0.66) and a more striking benefit in the ESR1-mutated subgroup (HR 0.43 vs. physician's choice of fulvestrant or exemestane) — the subpopulation where the FDA indication is anchored. Elacestrant (Orserdu) was the first oral SERD approved in 2023; imlunestrant adds a second option with a similar ESR1-mutated indication and the key advantage of the…

Related Therapies & Mechanisms

• Anastrozole (Arimidex) — Hormonal Agent · Breast
• Exemestane (Aromasin) — Hormonal Agent · Breast
• Fulvestrant (Faslodex) — Hormonal Agent · Breast
• Goserelin (Zoladex) — Hormonal Agent · Breast