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European Commission Approves Menarini's Orserdu for ESR1-Mutated Breast Cancer

NEW YORK – The Menarini Group on Wednesday said the European Commission has approved Orserdu (elacestrant) as a treatment for patients with estrogen receptor-positive, HER2-negative locally advanced or metastatic breast cancers bearing an activating ESR1 mutation who have progressed on at least one line of endocrine therapy including a CDK 4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor.

In July, the European Medicines Agency's Committee for Medicinal Products for Human Use recommended Orserdu in this setting based on results from the Phase III EMERALD trial, in which breast cancer patients with ESR1 mutations benefited more from Orserdu than standard-of-care treatment. Patients who received Orserdu had a median progression-free survival of 3.8 months compared to 1.9 months for those on the investigator’s choice of endocrine therapy, and Orserdu reduced the risk of progression or death by 45 percent.

A post hoc subgroup analysis of EMERALD results also showed that longer duration of prior CDK4/6 inhibitor therapy was positively associated with longer progression-free survival on Orserdu but not on the standard-of-care treatment. Among patients treated with CDK4/6 inhibitors for 12 months or more prior to enrolling in EMERALD, those who received Orserdu lived a median 8.6 months without disease progression compared to 1.9 months for the standard-of-care group and had a 59 percent reduction in the risk of progression or death.

The US Food and Drug Administration approved Orserdu in this indication in January 2023 alongside Guardant Health's Guardant360 CDx test to identify patients with ESR1 mutations who would be eligible for treatment.

ESR1 mutations are present in up to 40 percent of patients with ER-positive, HER2-negative metastatic breast cancer and are known to be a driver of resistance to standard endocrine therapy.