Genentech announced landmark clinical trial results demonstrating that giredestrant, an investigational selective estrogen receptor degrader (SERD), significantly outperforms standard endocrine therapy in treating early-stage ER-positive breast cancer. As reported by Drugs.com, the Phase III lidERA trial showed a remarkable 30% reduction in the risk of invasive disease recurrence or death, marking a major advancement in breast cancer treatment after nearly 25 years without new endocrine therapy breakthroughs.
The study enrolled over 4,100 patients with medium- to high-risk stage I-III ER-positive, HER2-negative breast cancer. At the three-year follow-up point, 92.4% of patients receiving giredestrant remained alive and free from invasive disease, compared to 89.6% in the standard-of-care endocrine therapy group. Beyond these primary findings, giredestrant demonstrated an additional 31% risk reduction in distant recurrence-free interval, reinforcing its efficacy across critical clinical endpoints.
Dr. Aditya Bardia, the trial’s principal investigator and director of the breast oncology program at UCLA, highlighted the clinical significance of these results. “After almost 25 years, a new medicine, giredestrant has demonstrated superiority over existing endocrine therapies in the curative setting,” he stated, emphasizing the potential for giredestrant to become a new standard-of-care option. The consistent iDFS benefit observed across all clinically relevant patient subgroups underscores the broad applicability of this new treatment approach.
ER-positive breast cancer represents approximately 70% of all breast cancer cases, with most diagnosed in early stages when the potential for cure is highest. Despite existing treatment options, the current standard endocrine therapies face significant limitations. Approximately one-third of patients experience disease recurrence after adjuvant endocrine therapy, while many others must discontinue treatment early due to tolerability or safety concerns, further increasing mortality risk. These challenges underscore the urgent clinical need that giredestrant addresses.
The mechanism of action distinguishes giredestrant from existing therapies. As an oral, next-generation SERD and full estrogen receptor antagonist, giredestrant blocks estrogen from binding to the estrogen receptor and triggers its degradation, effectively halting or slowing cancer cell growth. This represents a significant mechanistic advancement over current endocrine therapies.
The lidERA trial marks a pivotal milestone as the first and only oral SERD to demonstrate superior invasive disease-free survival in the adjuvant setting. This achievement follows giredestrant’s positive Phase III evERA trial results in metastatic breast cancer and builds upon earlier promising neoadjuvant data from the coopERA trial, which showed giredestrant’s superiority to aromatase inhibitors in reducing tumor cell proliferation.
Critically, giredestrant maintained an excellent safety and tolerability profile throughout the trial, with adverse events remaining manageable and consistent with its known profile. This is particularly important for adjuvant therapy, where patients require long-term treatment during their disease-free period.
While overall survival data remain immature, early analysis revealed a positive trend that supports continued follow-up monitoring. Genentech’s comprehensive giredestrant development program encompasses five Phase III trials spanning multiple treatment settings and disease stages, reflecting the company’s commitment to maximizing patient benefit across the ER-positive breast cancer spectrum. These results position giredestrant as a potentially transformative option for early-stage breast cancer patients seeking more effective, tolerable treatment alternatives.
