How Are Oral SERDs Changing the Management of Advanced HR-Positive Breast Cancer? Authors: Erica L. Mayer, MD, MPH; François-Clément Bidard, MD, PhD

https://www.medscape.org/viewarticle/how-are-oral-serds-changing-management-advanced-hr-positive-2025a1000xkg?page=1&sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity thank you for your recent participation in the activity: How Are Oral SERDs Changing the Management of Advanced HR-Positive Breast Cancer? Below are some key learning points to help reinforce the impact of this activity. ☑ Subsequent-line oral selective estrogen receptor degraders (SERDs) in HR-positive/HER2-negative breast cancer after endocrine therapy + CDK4/6 inhibitors • Single-agent SERDs ◦ The EMERALD phase 3 trial established elacestrant in patients with ESR1m ∙ Elacestrant vs endocrine therapy showed a significant PFS benefit (HR 0.546; 95% CI: 0.387, 0.768; P = .0005) ∙ Adverse events (AEs) more common with elacestrant included nausea, fatigue, and vomiting ◦ The EMBER-3 trial showed significantly improved PFS with imlunestrant vs standard of care endocrine therapy in patients with ESR1m (2.6 months difference in PFS; 95% CI: 1.2, 3.9; P < .0001), but no improvement in patients without ESR1m ∙ AEs more common with imlunestrant included fatigue, diarrhea, and nausea • SERDs in combination ◦ The EMBER-3 trial showed improved PFS with imlunestrant + abemaciclib vs imlunestrant alone in patients with/without ESR1m (HR = 0.57; 95% CI: 0.44, 0.73; P < .001) ∙ AEs common with the combination included diarrhea, nausea, and fatigue ◦ The evERA phase 3 trial showed significant improvement in PFS with giredestrant + everolimus vs standard of care endocrine therapy + everolimus in patients with ESR1m (HR 0.38; 95% CI: 0.27, 0.54; P < .0001) and patients with/without ESR1m (HR 0.56; 95% CI: 0.44, 0.71; P < .0001) ∙ AEs more common with the combination included nausea and decreased appetite ☑ Targeting ESR1m as they arise during first-line endocrine therapy + CDK4/6 inhibition, in the absence of clinical progression • SERENA-6 assessed switching from an aromatase inhibitor + CDK4/6 inhibition to camizestrant + CDK4/6 inhibition upon detection of ESR1m and significantly improved PFS following the switch compared with the continuation regimen (HR 0.44; 95% CI: 0.31, 0.60; P < .00001) ◦ AEs more common with camizestrant + CDK4/6 inhibition were photopsia and hematological AEs ◦ Additionally, camizestrant + CDK4/6 inhibition showed significantly better scores related to quality of life and patient-reported symptoms of cancer progression (pain, fatigue, and shortness of breath/dyspnea) ☑ Ongoing first-line trials in advanced/metastatic HR-positive/HER2-negative breast cancer • persevERA phase 3 trial: Giredestrant + palbociclib vs letrozole + palbociclib • SERENA-4 phase 3 trial: Camizestrant + palbociclib vs anastrozole + palbociclib