Erica Mayer, MD, MPH, FASCO, discussed SERDs and how they are transforming the treatment landscape for hormone receptor (HR)-positive/HER2-negative metastatic breast cancer. Unlike traditional therapies, oral SERDs not only block estrogen receptor (ER) activity, but also degrade the receptor, offering enhanced bioavailability, ease of administration, and effectiveness, particularly in cancers with ESR1 mutations.
The groundbreaking EMERALD study demonstrated that the oral SERD elacestrant significantly improved progression-free survival (PFS) compared with standard endocrine therapy (ET) in patients with ESR1-mutated cancers. Similarly, the EMBER-3 study highlighted the efficacy of imlunestrant in ESR1-mutated cancers, further solidifying the role of SERDs in advanced breast cancer.
These trials have paved the way for recent FDA approvals of elacestrant (February 2023) and imlunestrant (September 2025) as monotherapies for patients with ER-positive/HER2-negative ESR1-mutated metastatic breast cancer with disease progression and at least 1 line of ET, providing new options for pretreated patients. Though not approved as a combination therapy, readouts from EMBER-3 showed that imlunestrant in combination with abemaciclib was the first regimen to break the 6-month PFS barrier in the post–CDK4/6 inhibitor setting. Updated efficacy results from the EMBER-3 study for imlunestrant with and without abemaciclib will be presented at the San Antonio Breast Cancer Symposium on December 12, 2025.
Dr Mayer emphasized that "if a patient has both actionable mutations, such as ESR1 and PIK3CA, we can have confidence in selecting a SERD, either as monotherapy or in combination, to provide optimal results." The innovative SERENA-6 trial took a step further by testing early intervention with camizestrant at the onset of ESR1 mutations, prolonging PFS and delaying disease progression.
While oral SERDs are generally well tolerated, mild gastrointestinal disturbances and rare visual disturbances, such as photopsia, have been reported.
These advancements underscore the potential of SERDs, both as standalone therapies and in combination, to revolutionize breast cancer care and offer new hope to patients facing resistance to traditional treatments.
Source: Mayer E. Next generation endocrine agents. Presented at: San Antonio Breast Cancer Symposium 2025. December 9, 2025; San Antonio, TX. Presentation ED1-02.