FDA approved Orserdu (elacestrant) for ESR1-Mutated Advanced Breast CancerFDA approved new pill for advanced breast cancer with ESR1 mutation.

Elacestrant is an estrogen receptor antagonist that binds to estrogen receptors, including those with ESR1 mutations, and inhibits estrogen-dependent tumor growth.

Orserdu is indicated for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Selection is based on the presence of ESR1 mutations in plasma using an FDA-approved test.

The recommended dosage is 345 mg taken orally once daily with food. Dose reductions are 258 mg and 172 mg for adverse reactions. Avoid use with strong or moderate CYP3A4 inducers and inhibitors. For moderate hepatic impairment (Child-Pugh B), reduce dose to 258 mg once daily; avoid use in severe hepatic impairment (Child-Pugh C).

Efficacy was evaluated in EMERALD (NCT03778931), a randomized, open-label, active-controlled trial enrolling 478 patients with ER+/HER2- advanced or metastatic breast cancer, of which 228 had ESR1 mutations. Patients had progressed on one or two prior endocrine therapies including a CDK4/6 inhibitor. They were randomized 1:1 to Orserdu 345 mg daily or investigator's choice (fulvestrant or aromatase inhibitor). The major efficacy outcome was PFS by blinded independent review. A statistically significant PFS benefit was observed in the ITT population and in the ESR1-mutated subgroup. In patients without ESR1 mutations, PFS HR was 0.86 (95% CI: 0.63, 1.19), indicating the benefit was primarily in the ESR1-mutated population.

Not reported in label.

Orserdu is a new option for patients with ESR1-mutated, ER+/HER2- advanced or metastatic breast cancer after progression on at least one prior endocrine therapy, including a CDK4/6 inhibitor. It is the first therapy specifically targeting ESR1 mutations, which are associated with endocrine resistance.