Patients with estrogen-receptor-positive (ER+) HER-2-negative advanced breast cancer experienced significantly improved progression-free survival (PFS) when treated with an oral combination regimen that included giredestrant, a novel, next-generation selective ER degrader and full antagonist (SERD), compared to a standard combination approach. These findings, from the phase 3 evERA Breast Cancer study, were published today in the New England Journal of Medicine. Initial results of the evERA study were presented at the 2025 Congress of the European Society of Medical Oncology.
Tumors that express ER account for roughly 70% of all breast cancer and can be challenging to treat when metastatic. The advent of CDK 4/6 inhibitors has greatly improved outcomes for patients with metastatic disease, but treatments options for patients after these agents are no longer able to keep the cancer in check may be limited and less effective.
"There is an urgent need for new and more effective therapies for metastatic ER-positive breast cancers, particularly for patients whose tumors develop resistance to current endocrine therapies and who have progressed following treatment with CDK 4/6 inhibitors," said Erica Mayer, MD, MPH , Director of Breast Cancer Clinical Research at the Dana-Farber Cancer Institute and the Principal Investigator of the evERA study. "The results we are publishing today show that a novel combination regimen can substantially improve disease control compared to a standard of care regimen and may provide great benefit to a large number of patients with advanced breast cancer."
The evERA study is a global phase 3, randomized, open-label study evaluating the use of the oral SERD giredestrant in combination with everolimus, an mTOR targeting drug, in patients with ER-positive, HER-2-negative advanced breast cancer. This all-oral regimen is compared to a standard of care combination of endocrine therapy plus everolimus, and evERA is the first phase 3 study to compare a novel combination strategy to a standard of care combination regimen. The study was designed to look for improvement in progression-free survival (PFS) using the giredestrant-based regimen in all patients (intention to treat, ITT) and in the subset of patients whose tumor had an ESR1 mutation.
Giredestrant is a next-generation selective estrogen receptor degrader and full antagonist or SERD. It works by binding to the estrogen receptor and promoting its degradation, thus preventing estrogen from stimulating cancer growth.
A total of 373 patients were enrolled and randomized to receive either giredestrant plus everolimus or standard of care endocrine therapy and everolimus. About 55% of patients had mutations in the estrogen receptor gene (ESR1), indicating potential resistance to endocrine therapy.
With a median follow-up of 18.6 months, patients with tumors harboring an ESR1 mutation who received the giredestrant-containing regimen showed a statistically significant improvement in median PFS of 10 months, compared to 5.5 months for those who received the standard of care combination which corresponds to a 63% reduction in the risk of disease progression or death.
In the ITT population in the evERA study, which includes patients with ESR1 mutations and those without, the patients who received the giredestrant combination showed a statistically significant improvement in median PFS of 8.8 months compared to 5.5 months for those treated with the standard of care combination. That corresponds to a 44% reduction in the risk of disease progression or death.
"These results, including a near doubling of PFS in the ESR1 population, point to a highly effective new option for patients living with metastatic HR+ breast cancer." said Mayer.
The overall survival data from the study remain immature but are trending favorably. In addition, the safety profile of the giredestrant regimen was manageable and consistent with the known safety profiles of the individual study treatments.
Funding: The evERA Breast Cancer Study was funded by F. Hoffmann-La Roche Ltd.
