Camizestrant

ETCAMAH in combination with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) is indicated for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer upon detection of ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy, based on an FDA-authorized test. This indication is approved under accelerated approval based on progression-free survival as measured from detection of ESR1 mutation. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Camizestrant is an estrogen receptor (ER) antagonist. In vitro, camizestrant binds to the ligand binding domain of ERα, antagonizing the activity of ERα encoded by both wild-type ESR1 and mutated ESR1 and inducing proteasome-dependent degradation of ERα, without agonizing ERα. Camizestrant demonstrated anti-tumor activity in ER-positive cell lines, in vitro, and patient derived xenograft (PDX) models, in vivo, including those with wild-type or mutated ESR1 genes. Treatment with camizestrant and CDK4/6 inhibitors (abemaciclib, palbociclib, or ribociclib) demonstrated greater anti-tumor activity than single agent treatment in ER-positive cell lines and PDX models.

• Select patients for treatment with ETCAMAH based on the detection of ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy. • Recommended Dosage: 75 mg orally once daily with or without food. • See Full Prescribing Information for dosage modifications for adverse reactions. • Recommended dosage for patients with hepatic impairment differs depending on the CDK4/6 inhibitor used in combination with ETCAMAH.

None. None.

Boxed warning (arrhythmia risk with concomitant use of): QTc INTERVAL PROLONGING DRUGS ETCAMAH in combination with ribociclib, a QTc interval prolonging drug and a strong CYP3A inhibitor, or in combination with other QTc interval prolonging drugs, can increase the risk of Torsades de Pointes, other ventricular arrhythmias, and sudden death. • Bradycardia: Monitor heart rate more frequently during the first 30 days. Avoid concomitant use of ETCAMAH with other products known to cause bradycardia. Withhold or permanently discontinue ETCAMAH based on severity. • Embryo-Fetal Toxicity: ETCAMAH can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception.

The most common adverse reactions (≥ 20%), including laboratory abnormalities, with ETCAMAH in combination with a CDK4/6 inhibitor were decreased neutrophils, decreased leukocytes, decreased hemoglobin, decreased lymphocytes, decreased platelets, visual disturbances, and fatigue.

• CYP3A Inhibitors: Monitor for increased adverse reactions to ETCAMAH with strong CYP3A inhibitors and modify the dosage as recommended. • CYP3A Inducers: Avoid concomitant use of strong and moderate CYP3A inducers. If concomitant use with a moderate CYP3A inducer cannot be avoided, dose adjustment is needed when ETCAMAH is given in combination with abemaciclib or palbociclib. • CYP2C9 and/or CYP2C19 Substrates: Avoid concomitant use of ETCAMAH with CYP2C9 substrates or CYP2C19 substrates during treatment with ETCAMAH and at least 2 weeks after the last dose of ETCAMAH, unless otherwise recommended in the Prescribing Information of the CYP2C9 substrate or CYP2C19 substrate. • CYP3A Substrates: Refer to the Prescribing Information for CYP3A substrates where minimal increases in the concentration may lead to serious adverse reactions.

Store ETCAMAH at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F). Store and dispense ETCAMAH tablets in the original bottle with desiccant to protect from moisture. Alternatively, dispense ETCAMAH tablets in a USP equivalent tight container and discard after 30 days if stored without desiccant.