Dr Mayer on Giredestrant's Success in Early Breast Cancer

Erika Mayer, MD, MPH, Dana-Farber Cancer Institute, discusses the exciting findings of the phase 3 lidERA study investigating giredestrant presented at the 2025 San Antonio Breast Cancer Symposium.

Findings from the trial revealed that giredestrant significantly improves invasive disease-free survival (IDFS) in patients with ER-positive, HER2-negative early breast cancer. This study marks a milestone as the first trial in 25 years to demonstrate the superiority of a novel endocrine agent over the long-standing standard-of-care (SOC) endocrine therapy in this patient population.

The lidERA trial enrolled 4,170 patients with medium- to high-risk early breast cancer who were randomized to receive either 30 mg of daily oral giredestrant or SOC endocrine therapy (such as tamoxifen or aromatase inhibitors). After a median follow-up of 32.36 months, giredestrant demonstrated a 30% reduction in the risk of invasive disease recurrence or death compared to SOC (HR, 0.70). The three-year IDFS rate for giredestrant was 92.4%, compared to 89.6% for the SOC group. Exploratory analyses indicated that while giredestrant outperformed both tamoxifen and aromatase inhibitors, the benefit was particularly pronounced in patients previously treated with tamoxifen.

Subgroup analyses further confirmed that giredestrant’s efficacy was consistent across various demographics, including pre-menopausal patients and those with stage II disease. While interim overall survival (OS) data showed a numerical advantage for giredestrant (97.0% vs 95.9% at 36 months), these results have not yet reached statistical significance and remain immature.

Beyond efficacy, giredestrant maintained a favorable safety profile consistent with previous studies. Common side effects, such as hot flushes and arthralgia, were similar between the two groups; however, giredestrant was associated with a lower rate of treatment discontinuation. Experts suggest that these results establish giredestrant as a potential new frontline standard of care, offering a more effective and tolerable alternative for patients facing a high risk of recurrence.

REFERENCE

Bardia A, Schmid P, Martín M, et al. 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. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-10