FDA Approves Orserdu to Treat Metastatic Breast Cancer

The FDA has approved Orserdu (elacestrant) to treat postmenopausal women or adult men with advanced or metastatic breast cancer. It is indicated for patients with ER-positive, HER2-negative, ESR1-mutated disease with disease progression following at least one line of endocrine therapy.

Developed by Stemline Therapeutics (a subsidiary of Menarini Group), Orserdu is an oral selective estrogen receptor degrader (SERD). SERDs work by blocking the effects of estrogen on hormone receptor-positive breast cancer cells. ESR1 mutations are present in up to 40% of ER+, HER2- advanced or metastatic breast cancers.

In a press release, Stemline indicated that Orserdu will be available soon and the company will offer financial assistance.

Approval was based on data from the phase 3 EMERALD study, a multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer of which 228 patients had ESR1 mutations. The study compared Orserdu with AstraZeneca’s Faslodex (fulvestrant), the only other FDA-approved SERD, plus letrozole, anastrozole, exemestane.

In the 228 (48%) patients with ESR1 mutations, median progression-free survival was 3.8 months in the Orserdu arm and 1.9 months in the Faslodex arm. An exploratory analysis of progression-free survival in the 250 (52%) patients without ESR1 mutations showed a hazard ratio of 0.86, indicating that the improvement in the intent-to-treat population was primarily attributed to the results seen in the ESR1 mutated population.

The most common adverse events were musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.

In December 2022, additional data from the EMERALD study were reported at the San Antonio Breast Cancer Symposium (SABCS). Orserdu demonstrated progression-free survival of 8.6 months versus standard of care endocrine therapy.

Virginia Kaklamani, MD

“This suggests elacestrant may have the potential to become a new standard of care as a monotherapy endocrine sequencing option in ER+, HER2- advanced breast cancer after progression on CDK4/6i, before moving to combination therapies,” Virginia Kaklamani, MD, DSc, breast medical oncologist and professor of medicine, UT Health San Antonio, MD Anderson Cancer Center, said in a press release at the time.

The FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with Orserdu.