US FDA approves ORSERDU™ (elacestrant) for ER+, HER2- advanced or metastatic breast cancer
Breast cancer is the most common cancer affecting women; in the United States, approximately 13% of women will suffer from breast cancer at some point in their lives, with the vast majority of deaths resulting from metastatic breast cancers. Among these more aggressive cancer cases, up to 40% of ER+ and HER2- advanced or metastatic breast cancers containing ESR1 mutations.
ESR1 mutations are notoriously difficult to treat. Mutations within this gene are known to play a central role in resistance to endocrine therapy, one of the most common and effective treatments for hormone sensitive breast cancers, including those that are ER+. Consequently, the development of new therapeutic treatments that target this gene are of paramount importance.
On January 27, 2023, the FDA approved the use of ORSERDUTM (elacestrant) 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. The drug, developed by the Menarini Group (Florence, Italy), is the first ever therapy specifically for patients with ESR1 mutations in ER+, HER2- advanced or metastatic breast cancer.
Taken once a day as an oral pill, elacestrant is a selective estrogen receptor antagonist that blocks estrogen receptors in breast tissue, inhibiting the effect of estrogen on ER+ breast cancer cells.
Based on the results of the recent Phase III EMERALD trial, elacestrant was granted Priority Review and Fast Track Designation by the FDA. Results demonstrated statistically significant progression-free survival (PFS) when patients were treated with elacestrant compared to standard-of-care (SOC) endocrine monotherapy (letrozole, exemestane, fulvestrant, anastrozole).
Elacestrant decreased the risk of disease progression or death by 45% (95% CI) compared to SOC, in patients with tumors containing ESR1 mutations. In patients treated with a CDK4/6 inhibitor for a minimum of 12 months and whose tumors presented ESR1 mutations, the median PFS was 8.6 months when treated with elacestrant, compared to 1.9 months for SOC treatment.
Safety data from EMERALD is also promising, and congruous with other endocrine therapies. The majority of adverse events, such as muscoskeletal pain and nausea were Grade 1 and 2. Additionally, no hematological safety signal was detected and no patients in the two treatment groups exhibited sinus bradycardia.
Elacestrant has the potential to transform treatments for ESR1-mutated breast cancers. Aditya Bardia, Director of Breast Cancer Research at Mass General Cancer Center (MA, USA), states: “Advanced or metastatic ER+, HER2- breast cancer pre-treated with endocrine-based therapy remains an area of unmet medical need. 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.”