Sequencing, Safety, and the Evolving Role of Oral SERDs in HR+/HER2– mBC

Future Directions and Treatment Sequencing

Multiple oral selective estrogen receptor degraders (SERDs) are in development beyond elacestrant, including ongoing studies with everolimus combinations in European randomized controlled trials. The ELEGANT study is investigating elacestrant in early-stage breast cancer to prevent metastatic recurrence, potentially expanding treatment applications. Studies are also exploring elacestrant use in CDK4/6 inhibitor-naive patients who cannot tolerate these drugs due to age or comorbidities.

Additional development programs include camizestrant (SERENA-4 study) and other oral SERDs from various pharmaceutical companies. These agents may be developed as monotherapy or in combination with CDK4/6 inhibitors or immunotherapy. The expanding pipeline suggests continued evolution in ESR1-targeted therapy options for patients with hormone receptor–positive breast cancer.

Treatment sequencing principles emphasize exhausting endocrine plus targeted therapy options before transitioning to chemotherapy or antibody-drug conjugates (ADCs) due to superior quality of life with hormone-based treatments. However, rapid disease progression with ESR1 mutations may warrant closer monitoring with restaging at 6 to 8 weeks rather than the standard 3 to 4 months to ensure treatment efficacy before considering alternative approaches. Once patients receive chemotherapy or ADCs, a return to endocrine therapy becomes unlikely, making thorough exploration of hormone-based options crucial.