Oral SERD Giredestrant Cuts Risk of Invasive Recurrence by 30% in Early ER+ Breast Cancer

Presented at the 2025 SABCS annual meeting, the phase III lidERA trial showed that oral SERD giredestrant reduced the risk of invasive disease recurrence or death by 30% in early-stage ER-positive breast cancer, with three-year iDFS of 92.4% versus 89.6% on standard therapy. The benefit was consistent across subgroups, distant recurrence fell by 31%, and safety remained manageable, highlighting a potential new adjuvant standard.

Roche has unveiled phase III data showing that the investigational oral SERD giredestrant significantly reduces the risk of invasive disease recurrence or death in early-stage ER-positive breast cancer. The findings from the lidERA Breast Cancer study, presented during the 2025 San Antonio Breast Cancer Symposium, represent the first major advance in adjuvant endocrine therapy in more than two decades and position giredestrant as a potential new standard of care.

At the pre-specified interim analysis, giredestrant achieved a 30 percent reduction in the risk of invasive disease recurrence or death compared with standard endocrine therapy, with a hazard ratio of 0.70 and a p value of 0.0014. Investigators reported consistent benefit across all clinically relevant subgroups. At three years, 92.4 percent of patients in the giredestrant arm remained free of invasive disease compared with 89.6 percent in the standard therapy arm. Although overall survival data remain immature, analysts noted a clear positive trend, and follow-up is ongoing.

“In early ER-positive breast cancer, challenges with disease recurrence and treatment adherence mean there is an urgent need for more effective, tolerable endocrine therapies,” said Dr. Aditya Bardia, Director of the Breast Oncology Program at UCLA and principal investigator of the lidERA study. “After almost 25 years, a new medicine, giredestrant, has demonstrated superiority over existing endocrine therapies in the curative setting, highlighting its potential as a new standard-of-care endocrine therapy for patients with breast cancer.”

For clinicians, the efficacy signal carries particular weight because ER-positive breast cancer accounts for nearly 70 percent of cases worldwide. Despite effective endocrine therapies, up to one in three patients still relapse during or after standard adjuvant treatment. Tolerability challenges often force treatment interruptions, further increasing recurrence risk.

“The substantial efficacy observed with giredestrant in the lidERA trial underscores its potential to become a new standard-of-care endocrine therapy in ER-positive early-stage breast cancer, where the chance for cure is highest,” said Levi Garraway, MD, PhD, Roche’s CMO and Head of Global Product Development. “We look forward to sharing these results with health authorities around the world with the aim of bringing this new treatment option to patients as soon as possible.”

Beyond invasive disease-free survival, the therapy delivered a 31 percent reduction in distant recurrence, a key secondary endpoint. Safety findings were consistent with the known profile of giredestrant, and investigators described adverse events as manageable.

The lidERA trial enrolled more than 4,100 individuals with medium or high-risk stage I to III ER-positive, HER2-negative breast cancer. The study is part of Roche’s broad giredestrant programme, which spans five phase III trials across adjuvant, metastatic, endocrine-sensitive, and endocrine-resistant disease. The rationale builds on promising neoadjuvant data, including the coopERA trial, where giredestrant outperformed aromatase inhibition in reducing Ki67, a marker of malignant cell proliferation.

If approved, giredestrant would become the first oral SERD to demonstrate superiority in the adjuvant setting, reflecting a meaningful step forward for a large global patient population in need of more effective and more tolerable endocrine options.