Next-generation oral SERD therapy reduces the risk of breast cancer recurrence

Next-generation oral SERD therapy reduces the risk of breast cancer recurrence

In an international study led by UCLA, researchers showed that Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), when administered as adjuvant therapy in early-stage hormone receptor (HR)-positive, HER2-negative breast cancer (1-3), significantly reduced the risk of disease recurrence compared to standard hormonal therapies, long considered the backbone of treatment.

The finding suggests a potential new treatment option for the most common subtype of breast cancer, which accounts for about 70% of all cases and is most commonly diagnosed at stages 1, 2 or 3.

The results were announced today at the San Antonio Breast Cancer Symposium (SABCS) by global research leader Dr. Aditya Bardia, professor of medicine at the David Geffen School of Medicine at UCLA and director of Translational Research Integration at the UCLA Health Jonsson Comprehensive Cancer Center.

This is a very significant development and, given its magnitude, may be one of the most important advances in hormone receptor-positive breast cancer in recent years. For decades, tamoxifen and aromatase inhibitors have been the standard endocrine therapies, and these results show significant improvement with giredestrant. It has the potential to reshape clinical practice for a large proportion of breast cancer patients.”

Dr. Aditya Bardia, Professor of Medicine, David Geffen School of Medicine, UCLA

Many patients with this type of breast cancer are treated with surgery followed by endocrine therapy such as tamoxifen and aromatase inhibitors for at least five years after surgery to reduce the risk of recurrence. Although the overall survival rate is high, up to a third of patients experience cancer recurrence and have difficulty tolerating current treatments, which can make maintaining long treatment durations difficult.

Giredestrant is one of a newer class of drugs designed to block and degrade estrogen receptor signaling, a key growth driver in HR-positive tumors. Unlike older therapies, it is designed to more precisely disrupt the signaling pathways that help cancer cells persist.

To test whether this new therapy could significantly improve patient outcomes, researchers enrolled 4,170 people with HR-positive, HER2-negative breast cancer in the Phase III lidERA clinical trial. Participants were randomly assigned to receive either 30 milligrams of giredestrant (2084) or one of several standard endocrine therapies (2086) for up to five years. The average age of participants was 54 years and 59% were postmenopausal.

After a median follow-up of 32.3 months, researchers found that patients treated with giredestrant were 30% less likely to experience recurrence or progression of invasive disease. The study's secondary endpoint, distant disease-free survival - the time it takes for the cancer to spread to other organs - also favored giredestrant, with a 31% reduction in distant metastases.

Common side effects, including joint pain, hot flashes and headache, occurred at similar frequencies in both groups and were predominantly of mild severity. Fewer patients receiving giredestrant discontinued treatment due to adverse reactions (5.3% versus 8.2%). Mild, asymptomatic bradycardia occurred more frequently with giredestrant but rarely required intervention.

Longer follow-up is still needed, but if confirmed, the results could represent the first major change in adjuvant endocrine therapy for breast cancer in more than 25 years, according to Bardia.

“This represents an exciting advance for patients and the field,” Bardia said. "As clinicians, our goal is to prevent relapses and help patients live longer, healthier lives. These results bring us closer to that goal."

The experiment was carried out by F. Hoffmann-La Roche Ltd. financed.

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