146 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

Background

Adjuvant endocrine therapy (ET) is the mainstay treatment for estrogen receptor–positive, HER2-negative (ER+/HER2–) early breast cancer. However, up to one-third of patients eventually experience recurrence. Clinically, there is an unmet need for more tolerable and efficacious ET to improve adherence and patient outcomes. Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs and demonstrated superior antiproliferative activity vs anastrozole in the neoadjuvant coopERA breast cancer trial. Results of the prespecified interim analysis of the global, randomized lidERA breast cancer trial (NCT04961996) are presented.

Methods

Patients with stage I to III ER+/HER2– early breast cancer were randomly assigned 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and perimenopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years. The primary end point was invasive disease-free survival (IDFS). Key secondary end points were overall survival (OS), distant recurrence-free interval (DRFI), and safety.

Results

A total of 4170 patients were randomly assigned (August 2021–September 2023): 2084 to giredestrant; 2086 to standard-of-care ET. Median age was 54.0 years; 59.3% of patients were postmenopausal; 13.0%, 47.4%, and 39.6% had stage I, II, and III breast cancer, respectively. Median follow-up at clinical cutoff (August 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 (HR, 0.70; 95% CI, 0.57-0.87; P = .0014). 3-year IDFS rates were 92.4% and 89.6%, respectively. There was a trend toward 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 to 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.

Conclusions

The lidERA breast cancer trial is the first phase 3 trial to demonstrate benefit with an oral SERD in early breast cancer. Giredestrant treatment resulted in a statistically significant and clinically meaningful IDFS improvement vs standard-of-care ET in ER+/HER2– early breast cancer. OS trended in favor of the giredestrant arm, and DRFI was improved vs standard-of-care ET. The safety profile was favorable and consistent with known profiles, and the discontinuation rate was slightly lower with giredestrant compared with standard-of-care ET. Overall, the results support giredestrant as a potential new standard for patients with HR+ early breast cancer.