“Despite advancements with CDK4/6 inhibitor treatment in the first-line setting, many people with advanced breast cancer will eventually experience disease progression as their tumors become resistant to endocrine therapy,” said lead author Erica L. Mayer, MD, MPH, a medical oncologist at Dana-Farber Cancer Institute, in a news release on the data.2 “The evERA trial demonstrated that the giredestrant combination significantly delayed disease progression, potentially offering a promising all-oral treatment option in a setting where there remains a need for additional treatments to improve patient outcomes.”
What did the overall survival analysis show?
Overall survival (OS) data were immature at the time of the interim analysis, but a positive trend favored giredestrant/everolimus. Among patients with ESR1-mutated tumors (59% data maturity), the estimated 18-month OS rate was 71.5% (95% CI, 61.2%-81.7%) with giredestrant/everolimus vs 50.9% (95% CI, 38.4%-63.4%) with standard therapy/everolimus (HR, 0.62; 95% CI, 0.38-1.02). In the overall population (67% data maturity), the estimated 18-month OS rate was 75.1% (95% CI, 68.3%-81.9%) vs 62.0% (95% CI, 54.3%-69.7%), respectively (HR, 0.69; 95% CI, 0.47-1.00). Follow-up for OS is ongoing and will continue to the next analysis.
What was the safety profile of the combination?
Adverse events (AEs) occurred in 98.9% of patients who received giredestrant/everolimus and in 96.8% of those who received standard therapy/everolimus. The most common AEs in each arm were stomatitis (47.3% vs 48.9%), diarrhea (26.9% vs 22.6%), and anemia (23.6% vs 21.0%). The investigators reported that AEs were manageable and consistent with the known safety profiles of the individual agents, with no unexpected safety findings, including no photopsia and low rates of bradycardia.
What is the evERA design, and what is the regulatory status of giredestrant?
evERA is a phase 3, randomized, open-label, multicenter trial that randomly assigned 373 patients 1:1 to giredestrant plus everolimus or standard endocrine therapy with exemestane, fulvestrant, or tamoxifen plus everolimus, each given orally. Eligible patients had ER-positive, HER2-negative locally advanced or metastatic breast cancer with disease progression or recurrence after a CDK4/6 inhibitor plus endocrine therapy.
ESR1-mutated tumors, which develop in up to 40% of patients with ER-positive disease in the post-CDK4/6 inhibitor setting, were present in 55.5% of the overall population. Giredestrant is an investigational, oral, next-generation selective estrogen receptor degrader and full antagonist.
Based on the evERA data, the FDA accepted a new drug application (NDA) for giredestrant in combination with everolimus for patients with ER-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer, with a target action date of December 18, 2026. The FDA also accepted, under priority review, an NDA for adjuvant giredestrant in ER-positive, HER2-negative early breast cancer based on the phase 3 lidERA trial (NCT04961996), with a target action date of November 30, 2026.
References
- Mayer EL, Tolaney SM, Martín M, et al. Giredestrant plus everolimus in advanced breast cancer. N Engl J Med. 2026;395(13):1285-1298. doi:10.1056/NEJMoa2602457
- Roche’s giredestrant combination significantly improved progression-free survival in ER-positive advanced breast cancer in phase III evERA data published in The New England Journal of Medicine. News release. Roche. September 30, 2026. Accessed October 3, 2026. Accessed October 2, 2026. https://tinyurl.com/mss6chus
