STANDARD TREATMENT — First-line treatment of HR-positive, HER2-negative advanced breast cancer generally includes an aromatase inhibitor alone or in combination with a CDK 4/6 inhibitor (abemaciclib, palbociclib, or ribociclib).1 Mutations in ESR1, a gene that encodes for estrogen receptor-alpha, can develop during treatment with an aromatase inhibitor and are associated with resistance to estrogen deprivation therapy and disease progression. ESR1 mutations are uncommon at diagnosis but are present in nearly 40% of patients who have disease progression on an aromatase inhibitor. The oral selective estrogen degraders (SERDs) elacestrant (Orserdu) and imlunestrant (Inluriyo) are FDA-approved for treatment of estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer in adults with ESR1 mutations who had disease progression following at least one prior line of endocrine therapy. Imlunestrant was also recently approved for use with abemaciclib (Verzenio) for the same indication.2,3

MECHANISM OF ACTION — Camizestrant binds to and degrades estrogen receptor-alpha, inhibiting estradiol-mediated cell proliferation. It has demonstrated antitumor activity in ER-positive, HER2-negative breast cancers with ESR1 mutations.

A CLINICAL STUDY — Accelerated approval of camizestrant was based on the results of a double-blind, placebo-controlled trial (SERENA-6) in 315 adults with HR-positive, HER2-negative advanced breast cancer who had ESR1 mutations in ctDNA (detected by a blood test) but did not have disease progression while on first-line treatment with an aromatase inhibitor and a CDK 4/6 inhibitor for at least 6 months. Patients were randomized to continue their current regimen or switch to camizestrant 75 mg once daily plus their current CDK 4/6 inhibitor. After a median follow-up of 12.6 months, median progression-free survival was significantly longer in the camizestrant arm than in the standard treatment arm (16.0 vs 9.2 months).4

ADVERSE EFFECTS — The most common adverse effects of camizestrant plus a CDK 4/6 inhibitor in the SERENA-6 trial were neutropenia, lymphopenia, leukopenia, thrombocytopenia, decreases in hemoglobin levels, visual disturbances, and fatigue. Bradycardia and QT-interval prolongation have also been reported.4

DRUG INTERACTIONS — Camizestrant is a CYP3A substrate and a strong CYP2C9 and 2C19 inhibitor. Use of camizestrant with strong CYP3A inducers should be avoided; if concurrent use is necessary, adjustments in the dosage of camizestrant are required. Use of strong CYP3A inhibitors can increase camizestrant serum concentrations and the risk of adverse effects. Use of CYP2C9 or 2C19 substrates with camizestrant and for at least 2 weeks after the last dose of the drug should be avoided.5

The camizestrant label contains a boxed warning about a risk of QTc-interval prolongation, torsades de pointes, and sudden death when it is taken with QT-interval-prolonging drugs; use of QT-interval-prolonging drugs (other than ribociclib) with camizestrant should be avoided. Camizestrant can cause bradycardia; its use with drugs that lower heart rate can result in additive effects.

PREGNANCY AND LACTATION — Oral administration of camizestrant to pregnant rats was associated with embryofetal mortality and decreased pup weight and survival. Females with reproductive potential and male patients who have female partners with reproductive potential should use effective nonhormonal contraception during treatment with camizestrant and for 4 weeks or one week, respectively, after the last dose. Breastfeeding is not recommended during treatment with camizestrant and for one week after the last dose.

DOSAGE, ADMINISTRATION, AND COST — Etcamah is supplied in 75-mg tablets. The recommended dosage is 75 mg taken once daily until disease progression or unacceptable toxicity occurs. The label contains dosage adjustments that should be made if adverse effects occur. The dosing frequency should be reduced in patients with severe hepatic impairment (Child-Pugh C) taking ribociclib (but not palbociclib or abemaciclib). An ECG should be performed at baseline, every week for the first 2 weeks of treatment, and periodically thereafter. The wholesale acquisition cost (WAC) for a 28-day supply of Etcamah is $24,392.6

CONCLUSION — In one clinical trial in adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had ESR1 mutations detected in circulating tumor DNA (ctDNA) during treatment with an aromatase inhibitor and a CDK 4/6 inhibitor, switching to the oral selective estrogen receptor degrader (SERD) camizestrant (Etcamah) plus a CDK 4/6 inhibitor extended progression-free survival significantly more than continuing aromatase inhibitor treatment. Data on overall survival are needed.

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