Results from the Phase III lidERA clinical trial show that giredestrant, an adjuvant therapy for early-stage hormone receptor-positive (HR+), HER2-negative breast cancer, significantly reduced the risk of recurrence compared to standard endocrine therapies after surgery. Presented today at the San Antonio Breast Cancer Symposium (SABCS), these findings could mark the first major shift in adjuvant therapy for breast cancer in over 25 years.
“This is perhaps one of the most important breast cancer advances in recent years for hormone receptor-positive disease,” said Aditya Bardia, MD, MPH, professor of medicine at the University of California, Los Angeles (UCLA), director of translational research integration at the UCLA Jonsson Comprehensive Cancer Center, and principal investigator of the trial. “For decades, tamoxifen and aromatase inhibitors have been the standard endocrine therapies. [Giredestrant] has the potential to reshape clinical practice for a large proportion of patients with breast cancer.”
Giredestrant is a next-generation oral selective estrogen receptor antagonist and degrader (SERD), a class of drugs that bind to the estrogen receptor and recruit cellular machinery to degrade it, inhibiting estrogen signaling that drives tumor growth. Bardia, who has conducted extensive work in development of new therapeutics and diagnostics for breast cancer, also led the clinical development of elacestrant, which became the first oral SERD to receive FDA approval in 2023.
While previous SERDs have been approved to treat breast cancer patients who have not responded to standard endocrine therapy, giredestrant is the first to show superiority over the standard of care. These new Phase III results endorse its potential as an alternative first-line adjuvant therapy for recurrence prevention after surgery in HR+ HER2- breast cancer patients.
“For patients with HR-positive breast cancer—which accounts for about 70% of breast cancer cases—effective adjuvant therapy at the early stage offers a real opportunity to eradicate micrometastatic disease and improve survival in the curative setting,” said Bardia. “Currently, up to a third of these patients eventually experience recurrence on or after adjuvant endocrine therapy for early breast cancer, and many struggle with tolerating treatment. A more effective, more tolerable treatment option is needed.”
The lidERA study enrolled 4,170 patients with stage 1-3 HR+ HER2- breast cancer who had undergone surgery in the past year. Half of the participants were treated with giredestrant, while the other half received one of four standard endocrine therapies—tamoxifen, letrozole, anastrozole or exemestane—as prescribed by their physician. Patients were treated either until five years had passed or until toxicity was too high to continue the treatment.
Results showed that patients who received giredestrant were 30% less likely to experience recurrence or progression compared to the standard of care. The oral SERD also reduced by 31% the likelihood of developing a distant metastasis.
Common side effects such as hot flashes, headaches and joint aches were reported at similar rates in both treatment groups. Bradycardia, a known side effect of SERDs that slows down the heart rate, was more commonly found among those who took giredestrant, with most cases reported to be asymptomatic, and all resolved. Overall, patients treated with giredestrant were less likely to discontinue treatment due to side effects, with 5.3% of participants quitting compared to 8.2% in the group who received the standard of care.
“Giredestrant demonstrated clinically meaningful superiority to currently well-established standard-of-care endocrine agents: aromatase inhibitors and tamoxifen,” said Bardia. “This represents an exciting advance for patients and the field. As clinicians, our goal is always to prevent recurrence and help patients live longer, healthier lives, and these results bring us closer to that.”
