European Commission Approves Elacestrant for Pretreated, ESR1+, ER+/HER2– Breast Cancer

September 20, 2023

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The European Commission has approved elacestrant for the treatment of postmenopausal women and men with estrogen receptor–positive, HER2-negative, locally advanced, or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least 1 line of endocrine therapy including a CDK4/6 inhibitor.

Elcin Barker Ergun

The European Commission has approved elacestrant (Orserdu) for the treatment of postmenopausal women and men with estrogen receptor (ER)–positive, HER2-negative, locally advanced, or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least 1 line of endocrine therapy including a CDK4/6 inhibitor.¹

The approval was based on data from the phase 3 EMERALD trial (NCT03778931), in which treatment with elacestrant led to a statistically significant improvement in progression-free survival (PFS) compared with investigator’s choice of an approved endocrine monotherapy in the overall population and in patients with ESR1 mutations. In the latter population, the median PFS was 3.8 months with elacestrant vs 1.9 months with standard of care (SOC; HR, 0.55; 95% CI, 0.39-0.77).

“We have long known that patients living with metastatic breast cancer need effective and tolerable options which treat their disease while enabling them to focus on the things that matter to them,” Elcin Barker Ergun, chief executive officer of the Menarini Group, stated in a news release. “We are proud of delivering a new breast cancer treatment that offers efficacy in a once-daily pill and represents the first innovation in endocrine therapy in nearly two decades; we are also incredibly grateful for the support of the oncology researchers and all the patients who participated in the clinical studies that made today’s achievement possible.”

In January 2023, elacestrant received FDA approval 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 1 line of endocrine therapy.²

FDA approval was also based on data from EMERALD, which enrolled patients with ER-positive, HER2-negative breast cancer who had progressed on 1 to 2 lines of endocrine therapy, including 1 line that contained a CDK4/6 inhibitor. One line of prior chemotherapy was allowed in the advanced or metastatic setting.

Eligible patients were randomly assigned to receive 345 mg of oral elacestrant once daily (n = 239) or investigator’s choice of endocrine therapy, including fulvestrant (Faslodex; n = 166) or an aromatase inhibitor such as anastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin; n = 73). Treatment was administered until progressive disease or intolerable toxicity.

Additional results from a post hoc subgroup analysis presented at the 2022 San Antonio Breast Cancer Symposium demonstrated improved PFS with elacestrant in patients who had received prior CDK4/6 inhibition for at least 12 months, at 8.6 months vs 1.9 months with SOC (HR, 0.41; 95% CI, 0.26-0.63).

The safety profile of the agent was consistent with prior data. The most common adverse effects that occurred in at least 10% of patients were nausea, increased triglycerides, increased cholesterol, vomiting, fatigue, dyspepsia, diarrhea, decreased calcium, back pain, increased creatinine increase, arthralgia, decreased sodium, constipation, headache, hot flush, abdominal pain, anemia, decreased potassium, and increased alanine aminotransferase.

“With a significant number of [patients with] ER-positive/HER2-negative [disease] ultimately developing ESR1 mutations at some point in their metastatic journey, it is important to test for ESR1 each time a [patient with] metastatic breast cancer experiences disease progression, to understand what is fueling their breast cancer. Today’s approval gives us the first-ever treatment option that directly acts against the very mutations that make this form of breast cancer more difficult to treat, and provides hope to our patients and their families,” Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milano and the head of the Division of Early Drug Development at the European Institute of Oncology, IRCCS, Italy, said.