Micrograph of metastatic breast cancer to lymph node
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Stemline Therapeutics, a subsidiary of pharma and diagnostics company Menarini Group, has received approval from the FDA for elacestrant (trade name Orserdu) for the treatment of postmenopausal women or adult men with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

Orserdu was approved under the FDA’s Priority Review and Fast Track designation based on results of its registrational Phase III EMERALD study which showed statistically significant progression-free survival (PFS) vs SOC endocrine monotherapy (fulvestrant, letrozole, anastrozole, exemestane). It met both primary endpoints in the study in all patients and in those patients with tumors with ESR1 mutations.

The EMERALD Phase III trial is a randomized, open label, active-controlled study evaluating elacestrant as second- or third-line monotherapy in ER+, HER2- advanced/metastatic breast cancer patients. The study enrolled 478 patients who had received prior treatment with one or two lines of endocrine therapy, including a CDK4/6 inhibitor. Patients in the study were randomized to receive either elacestrant or the investigator’s choice of an approved hormonal agent. The primary endpoints of the study were progression-free survival (PFS) in the overall patient population and in patients with estrogen receptor 1 gene (ESR1) mutations.

“Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. The last endocrine therapy approved was about 20 years ago, and effective endocrine options for this patient population are needed,” said Aditya Bardia, MD, director of breast cancer research at Mass General Cancer Center and principal investigator for the EMERALD trial. “ESR1 mutations are a known driver of resistance to standard endocrine therapy, and so far, have been difficult to treat. The approval of elacestrant is welcomed as it offers a novel option for patients with ER+, HER2- metastatic breast cancer. This therapy targets the ESR1 mutations in metastatic breast cancer and provides patients with a convenient oral once-daily dose.”

The study showed that in the group of clinical study patients whose tumors had ESR1 mutations, elacestrant reduced the risk of death or disease progression by 45% vs SOC. The PFS with elacestrant was 8.6 months compared with 1.9 months for SOC in patients with ESR1 mutations who had been treated with a CDK4/6i for at least 12 months.

Safety of the drug is consistent with other endocrine therapies with most of the adverse events including grade 1 and grade 2 nausea and musculoskeletal pain. There we no hemotological safety signals observed and neither or the two treatment arm patients had sinus bradycardia.

Orserdu will soon be available in the U.S. and will be commercialized by Stemline. To that end, the company announced that Stemline ARC, a patient support program, will provide educational information to help them understand their insurance coverage and identify potential financial assistance options.

In related news, Guardant Health announced that it received FDA approval for its Guardant360 CDx liquid biopsy test as a companion diagnostic to identify advanced or metastatic breast cancer patients with ESR1 mutations who may benefit from treatment with Orserdu.

“This FDA approval is great news for breast cancer patients with ESR1 mutations, who now have, for the first time, an approved treatment for their specific type of cancer and a blood-based companion diagnostic,” said Helmy Eltoukhy, Guardant Health co-CEO.

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