A next-generation oral therapy, giredestrant, has been shown to significantly lower the risk of breast cancer returning in early-stage patients, according to an international study led by UCLA researchers. The drug, a selective estrogen receptor degrader (SERD), was tested as adjuvant therapy for hormone receptor (HR)-positive, HER2-negative breast cancer, the most common subtype, which accounts for about 70% of all cases.
The findings were presented at the San Antonio Breast Cancer Symposium (SABCS) by Dr. Aditya Bardia, professor of medicine at the David Geffen School of Medicine at UCLA and director of Translational Research Integration at UCLA Health Jonsson Comprehensive Cancer Center.
Currently, many patients with this breast cancer subtype undergo surgery followed by endocrine therapy—such as tamoxifen or aromatase inhibitors—for at least five years to reduce recurrence risk. While overall survival rates are high, up to a third of patients experience a return of the disease and often face challenges tolerating long-term treatment.
Giredestrant belongs to a new class of drugs designed to block and dismantle estrogen receptor signaling, a key driver of HR-positive tumor growth. Unlike older therapies, it more precisely targets pathways that allow cancer cells to survive.
The phase III lidERA trial enrolled 4,170 patients with HR-positive, HER2-negative breast cancer. Participants were randomly assigned to receive either 30 milligrams of giredestrant (2,084 patients) or standard endocrine therapy (2,086 patients) for up to five years. The median age was 54, and 59% of participants were postmenopausal.
After a median follow-up of 32.3 months, patients taking giredestrant were 30% less likely to experience invasive disease recurrence or progression. Secondary analysis showed a 31% reduction in distant metastases, indicating improved distant disease-free survival.
Side effects—including joint aches, hot flashes, and headaches—were generally mild and occurred at similar rates in both groups. Fewer patients discontinued giredestrant due to side effects (5.3% vs. 8.2%). Mild, asymptomatic bradycardia was more common with giredestrant but rarely required treatment.
Dr. Bardia noted that longer follow-up is needed but said the results could represent the first major change in adjuvant endocrine therapy for breast cancer in over 25 years. “This represents an exciting advance for patients and the field,” he said. “Our goal is always to prevent recurrence and help patients live longer, healthier lives, and these results bring us closer to that.”
The trial was funded by F. Hoffmann-La Roche Ltd.
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