Abstract GS1-10: Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial

Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr). The primary endpoint was invasive disease-free survival (IDFS). Key secondary endpoints were overall survival (OS), distant recurrence-free interval (DRFI), and safety.

4170 pts were randomized (Aug 2021-Sep 2023): 2084 to giredestrant; 2086 to standard-of-care ET. Median age was 54.0 yr; 59.3% of pts were postmenopausal; 13.0%, 47.4%, and 39.6% had Stage I, II, and III BC, respectively. Median follow-up at clinical cutoff (Aug 8, 2025) was 32.3 months, with 336 IDFS events. Efficacy is shown in the table. Giredestrant demonstrated superior IDFS vs standard-of-care ET (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.57, 0.87; p = 0.0014). 3-yr IDFS rates were 92.4% and 89.6%, respectively. There was a trend towards OS improvement in the giredestrant arm vs the standard-of-care ET arm (HR 0.79; 95% CI, 0.56,1.12). The DRFI HR was 0.69 (95% CI, 0.54, 0.89). The most common adverse events (AEs) in the giredestrant vs standard-of-care ET arms, respectively, were arthralgia (48.0% vs 47.1%), hot flush (27.4% vs 28.8%), and headache (15.3% vs 13.2%); the most common Grade 3-4 AEs, hypertension (2.6% vs 2.0%) and arthralgia (1.5% vs 1.8%). Discontinuations due to AEs occurred in 5.3% with giredestrant vs 8.2% with standard-of-care ET.