Dr Bardia on the Efficacy of Giredestrant in ER+, HER2-Negative Early Breast Cancer

“If [giredestrant] becomes FDA approved, it’ll provide a novel endocrine therapy option for patients with stage I to stage III ER-positive, HER2-negative, localized breast cancer.”

Aditya Bardia, MD, MPH, FASCO, a professor in the Department of Medicine in the Division of Hematology/Oncology, the director of Translational Research Integration, and a member of Signal Transduction and Therapeutics at the UCLA Health Jonsson Comprehensive Cancer Center, discussed key efficacy and safety findings from the phase 3 lidERA trial (NCT04961996) investigating giredestrant (GDC-9545) in patients with stage I to stage III estrogen receptor (ER)–positive, HER2-negative localized breast cancer.

Data from this trial were presented at the 2025 San Antonio Breast Cancer Symposium. This study compared giredestrant, a novel oral endocrine therapy, with standard-of-care (SOC) endocrine therapy—either aromatase inhibitors or tamoxifen. The trial aimed to address a significant unmet need, as this subtype accounts for over 70% of early breast cancers, and up to 25% of patients currently experience recurrence within 5 years of starting traditional endocrine therapy.

The open-label study enrolled 4170 patients, with 2084 patients randomly assigned to receive oral giredestrant at 30 mg daily and 2086 patients assigned to SOC endocrine therapy. In the control arm, 84% of patients received aromatase inhibitors, whereas 16% of patients received tamoxifen. The primary end point was invasive disease–free survival (IDFS), with key secondary end points including distant recurrence–free interval (DRFI) and overall survival (OS). Bardia highlighted that the lidERA trial was the first to demonstrate a benefit with a novel endocrine therapy in patients with early breast cancer since the introduction of aromatase inhibitors in the early 2000s.

The efficacy results showed that giredestrant provided a statistically significant and clinically meaningful improvement over SOC. The HR for IDFS was 0.70 (95% CI, 0.57-0.87; P = .0014), representing a 30% reduction in the risk of disease recurrence or death. At a median follow-up of 32.3 months, the 3-year IDFS rate was 92.4% with giredestrant vs 89.6% with SOC endocrine therapy. Furthermore, giredestrant improved DRFI with a HR of 0.69 (95% CI, 0.54-0.89), which reflects a 31% reduction in the risk of developing metastatic disease. Although interim OS data were immature, there was a positive trend favoring the giredestrant arm (stratified HR, 0.79; 95% CI, 0.56-1.12; P = .1863).

The safety profile of giredestrant was comparable with that of SOC endocrine therapy, but with notable advantages in certain areas. The rate of treatment discontinuation due to adverse effects was lower with giredestrant (5.3%) than with SOC endocrine therapy (8.2%). Discontinuations stemming from musculoskeletal symptoms (1.8% vs. 4.4%) and hot flushes (< 0.1% vs. 0.8%) were also less frequent in the giredestrant group vs the endocrine therapy group. Bardia concluded that giredestrant potentially offers a novel and better-tolerated endocrine therapy option for patients with localized, ER-positive breast cancer.