Giredestrant Improves Outcomes in ER+/HER2– Breast Cancer

Among patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, medium- and high-risk early breast cancer, giredestrant (GDC-9545) improved invasive disease-free survival (IDFS) versus standard-of-care (SOC) endocrine therapy, according to findings from the phase 3 lidERA breast cancer trial presented at the 2025 San Antonio Breast Cancer Symposium (SABCS).

Efficacy data from the trial revealed that in patients treated with giredestrant or SOC endocrine therapy, a significant and clinically meaningful improvement in IDFS was observed with the investigational therapy with a 30% reduction in the risk of invasive disease recurrence or death after a median follow-up of 32.36 months. Additionally the respective 12 month 24 month and 36 month IDFS rates in the giredestrant arm were 97.7% 94.6% and 92.4%. In the SOC arm the respective rates were 96.9% 92.3% and 89.6%.

An exploratory analysis examining IDFS by SOC endocrine therapy regimens revealed that aromatase inhibitors displayed more favorable efficacy versus tamoxifen.

A subgroup analysis revealed that the IDFS benefit was consistent across all key prespecified subgroups. Particular benefit was observed among patients 46 to 55 years old patients with American Joint Committee on Cancer stage II disease at surgery patients who did not receive prior chemotherapy and premenopausal patients.

Additionally interim overall survival (OS) data revealed a numerically improved advantage with giredestrant although the data were immature at the time of analysis. The respective 12 month 24 month and 36 month OS rates in the giredestrant and SOC arms were 99.5% versus 99.4% 98.2% versus 97.5% and 97% versus 95.9%.

“Since the approval of aromatase inhibitors in 2000 25 years later the lidERA breast cancer trial is the first trial that has demonstrated benefit with a novel endocrine agent in early breast cancer,” Dr. Aditya L. Bardia, stated in the press briefing. “With a median follow-up of 32.6 months lidERA demonstrated a clinically meaningful and statistically significant improvement with frontline giredestrant over SOC endocrine therapy in estrogen receptor-positive human epidermal growth factor receptor 2-negative early breast cancer.”

Those enrolled on the phase 3 trial had stage 2 to 3 estrogen receptor-positive human epidermal growth factor receptor 2-negative disease had received breast cancer surgery within 12 months of the start of study treatment and received adjuvant or neoadjuvant chemotherapy if indicated. Patients were stratified by medium versus high-risk disease region receipt of previous chemotherapy and menopausal status.

The primary end point of the trial was invasive disease-free survival excluding second primary non-breast cancer. Secondary end points included disease-free survival distant recurrence-free survival IDFS including second primary non-breast invasive cancer overall survival and safety.

In the safety evaluable population of the giredestrant and endocrine therapy arms the most common treatment-emergent side effects included arthralgia 46.5% versus 45.3% hot flush 27.1% versus 28.5% and headache 15.2% versus 13.1%. Arthralgias and hot flushes resulting in treatment discontinuations in the respective arms occurred in 1.6% versus 3.7% and less than 0.1% versus 0.8% of patients. Of note no patients in either arm experienced grade 3 or 4 bradycardia and less than 0.1% versus 0.3% of each arm experienced grade 3 or 4 venous thromboembolic events.

“The safety profile was favorable and consistent with the known profile. The discontinuation rate was lower with giredestrant compared with standard-of-care endocrine therapy,” Bardia concluded.

Reference

1. “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,” by Dr. Aditya L. Bardia, et al. Presented at: 2025 San Antonio Breast Cancer Symposium; Dec. 9-12, 2025; San Antonio, TX. Abstract GS1-10.

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