IMLUNESTRANT TAB

Clinical Criteria Summary

Adults with ER+, HER2-negative, ESR1-mutated (ESR1m) advanced or metastatic breast cancer (MBC)
Disease progression following at least one line of endocrine therapy (ET)
Specifically evaluated in patients who recurred or progressed during or after aromatase inhibitor therapy (alone or with a CDK4/6i)

Recommended dosage: 400 mg orally once daily until progressive disease (PD) or unacceptable toxicity
Administer on an empty stomach
Dose reduction to 200 mg once daily required for moderate to severe hepatic impairment

Contraindications: None
Embryo-Fetal Toxicity (EFT): Potential fetal harm; verify pregnancy status prior to initiation
Advise patients of reproductive potential to use effective contraception during treatment and for 1 week after the last dose
Advise not to breastfeed during treatment and for 1 week after the final dose

Strong CYP3A Inhibitors: Avoid concomitant use; if unavoidable, decrease imlunestrant dosage
Strong CYP3A Inducers: Avoid concomitant use; if unavoidable, increase imlunestrant dosage
P-gp or BCRP Substrates: Avoid concomitant use where minimal concentration changes may lead to serious adverse reactions (imlunestrant inhibits these transporters)
Renal Impairment: No clinically significant PK differences in mild or moderate impairment; effects on PK unknown in severe impairment
Hepatic Impairment: No dosage modification for mild impairment; reduce to 200 mg once daily for moderate to severe impairment

FDA-approved for HR+, HER2- advanced or metastatic breast cancer (specifically ESR1m population)
NCCN Classification: "Other recommended"; Category 2A; indicated for PD on/after prior line following aromatase inhibitor +/- CDK4/6i in adjuvant or metastatic setting
VA Breast Cancer Pathway v2.2026 positions similar agents (e.g., elacestrant) in this therapeutic space
Combination with abemaciclib demonstrated improved PFS over monotherapy regardless of ESR1 mutation status, but this combination is not part of FDA-approved labeling

Most common adverse events (>10%): Decreased hemoglobin, musculoskeletal pain, decreased calcium, decreased neutrophils, increased AST, fatigue, diarrhea, increased ALT, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain
Monotherapy safety profile comparable to standard ET; treatment discontinuations due to adverse events infrequent (4.6% vs 1.2%)
Addition of abemaciclib increases adverse event incidence; diarrhea is most common (86% any grade, 8% > grade 3) but manageable with dose adjustments or supportive care

Advanced or metastatic breast cancer
Hormone receptor (HR) positive, HER2-negative breast cancer
ESR1-mutation positive as detected by an approved test
Progressive disease on or after at least one endocrine-based regimen (i.e. aromatase inhibitor +/- CDK 4/6 inhibitor)

Care is provided by a VA or VA Community Care oncology provider
Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
Goals of care and role of Palliative Care consult have been discussed and documented

For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for one week after stopping treatment.
For females who are lactating / providing breastmilk to an infant or planning to do so: Counseling provided to avoid breastfeeding during treatment and for one week after stopping treatment.