Roche reports Phase III evERA results showing giredestrant plus everolimus improved progression-free survival in ER-positive, HER2-negative advanced breast cancer.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
Roche has reported detailed Phase III evERA Breast Cancer results showing that investigational giredestrant plus everolimus significantly improved progression-free survival (PFS) compared with standard endocrine therapy plus everolimus in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor and endocrine therapy. The results were published in The New England Journal of Medicine on October 1, 2026.
Giredestrant Combination Improves Progression-Free Survival
In the ESR1-mutated population, median PFS was 10.0 months with giredestrant plus everolimus compared with 5.5 months with standard endocrine therapy plus everolimus. The treatment reduced the risk of disease progression or death by 62% (HR 0.38; 95% CI, 0.27–0.54; p<0.001).
In the intent-to-treat (ITT) population, median PFS was 8.8 months versus 5.5 months, respectively, corresponding to a 44% reduction in the risk of disease progression or death (HR 0.56; 95% CI, 0.44–0.71; p<0.001).
Overall Survival Data Remain Immature
Overall survival (OS) data were immature at the time of analysis. A positive trend was observed in both the ITT population (HR 0.69; 95% CI, 0.47–1.00) and the ESR1-mutated population (HR 0.62; 95% CI, 0.38–1.02). Roche said OS follow-up will continue to the next analysis.
Safety Profile Consistent with Known Treatments
Adverse events associated with the giredestrant combination were manageable and consistent with the known safety profiles of the individual medicines. Roche reported no unexpected safety findings, including no photopsia and low rates of bradycardia.
Benefit Observed Beyond Initial Progression
Additional analyses presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting showed that giredestrant plus everolimus prolonged PFS2, defined as the time from randomisation to disease progression following second-line therapy, as well as chemotherapy-free survival compared with standard endocrine therapy. The findings suggest that the treatment benefit may extend beyond initial disease progression.
Clinical Need in ER-Positive Breast Cancer
Hormone receptor-positive, HER2-negative breast cancer accounts for approximately 70% of breast cancer cases. Endocrine resistance, particularly following CDK4/6 inhibitor treatment, remains a major challenge and can lead to disease progression and limited treatment options. In the post-CDK4/6 inhibitor setting, ESR1 mutations occur in up to 40% of patients with ER-positive disease.
Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist designed to block estrogen binding to the estrogen receptor and trigger receptor degradation.
FDA Regulatory Status
Based on the evERA results, the FDA has accepted Roche’s New Drug Application (NDA) for giredestrant plus everolimus in adults with ER-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease has recurred during or after adjuvant endocrine therapy or progressed following at least one endocrine-based regimen in the metastatic setting. The FDA’s PDUFA goal date is December 18, 2026.
The FDA has also accepted an NDA under Priority Review for giredestrant as adjuvant treatment for adults with ER-positive, HER2-negative stage I, II and III breast cancer based on Phase III lidERA results. The PDUFA goal date is November 30, 2026.
About the evERA Study
evERA (NCT05306340) is a Phase III, randomised, open-label, multicentre study evaluating giredestrant plus everolimus versus standard endocrine therapy plus everolimus in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor and endocrine therapy, either in the adjuvant or advanced-disease setting. The co-primary endpoints are investigator-assessed PFS in the ITT and ESR1-mutated populations.
The evERA study represents the first positive Phase III readout for giredestrant, followed by the Phase III lidERA study in early-stage breast cancer. Roche is evaluating giredestrant across five Phase III studies covering different breast cancer settings and treatment lines.
Reference
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, Roche, 01 October 2026
A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared with the Physician’s Choice of Endocrine Therapy Plus Everolimus in Participants with Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer), ClinicalTrials.gov ID NCT05306340
Erica L. Mayer et al, Giredestrant plus Everolimus in Advanced Breast Cancer, N Engl J Med 2026;395:1285-1298, https://www.nejm.org/doi/full/10.1056/NEJMoa2602457
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.