Giredestrant and everolimus significantly extend progression free survival in ER positive advanced breast cancer in phase III evERA results published in The New England Journal of Medicine

Detailed results from the evERA Breast Cancer study have been published in The New England Journal of Medicine. They show that Roche’s investigational oral selective oestrogen receptor degrader giredestrant, given with everolimus, significantly improved progression free survival compared with standard endocrine therapy plus everolimus. The trial enrolled people with oestrogen receptor positive locally advanced or metastatic breast cancer whose disease had progressed or returned after treatment with a CDK4/6 inhibitor and endocrine therapy.

Adding giredestrant cut the risk of disease progression or death by 44 per cent in the intent to treat population and by 62 per cent among patients with ESR1 mutations. In the ESR1 mutated group, median progression free survival was 10.0 months with giredestrant plus everolimus against 5.5 months for the comparator (stratified HR=0.38; 95% CI 0.27 to 0.54; p<0.001). In the intent to treat population, it was 8.8 months against 5.5 months (HR=0.56; 95% CI 0.44 to 0.71; p<0.001).

Overall survival data were still immature at the time of analysis, though a clear positive trend appeared in both the intent to treat group (HR=0.69; 95% CI 0.47 to 1.00) and the ESR1 mutated group (HR=0.62; 95% CI 0.38 to 1.02). Follow up for overall survival will carry on to the next analysis. Side effects were manageable and in line with the known profiles of each medicine. There were no unexpected safety findings, no photopsia and low rates of bradycardia.

Dr Erica L. Mayer, a medical oncologist at Dana-Farber Cancer Institute, said that although CDK4/6 inhibitors have improved first line treatment, many people with advanced breast cancer eventually see their disease progress as tumours become resistant to endocrine therapy. She said evERA showed the giredestrant combination significantly delayed progression, potentially offering a promising all oral option in a setting where more treatments are still needed to improve outcomes.

Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, described the evERA results as an important step forward for people with ER positive advanced breast cancer, showing giredestrant’s potential to tackle progression in this setting. Together with the positive phase III lidERA results in early breast cancer, he said, the findings strengthen the case for giredestrant to change care in both metastatic and early disease.

Further evERA analyses were presented at the 2026 American Society of Clinical Oncology Annual Meeting. They showed that giredestrant plus everolimus lengthened PFS2, the time from randomisation to progression after second line therapy, as well as chemotherapy free survival compared with standard endocrine therapy, which suggests the benefit may continue beyond first progression.

Hormone receptor positive, HER2 negative disease makes up about 70 per cent of breast cancers. Resistance to endocrine therapy, especially after a CDK inhibitor, raises the risk of progression and is linked to poor outcomes.

evERA was the first positive phase III readout for giredestrant, followed by the lidERA Breast Cancer study in early stage disease. Based on the evERA data, the US Food and Drug Administration has accepted Roche’s New Drug Application for giredestrant with everolimus in people with ER positive, HER2 negative, ESR1 mutated locally advanced or metastatic breast cancer whose disease has recurred during or after endocrine based adjuvant therapy, or has progressed on at least one endocrine based regimen in the metastatic setting. A decision is expected by 18 December 2026. The agency has also accepted, under Priority Review, an application for giredestrant as adjuvant treatment in adults with ER positive, HER2 negative, stage I, II and III breast cancer based on the lidERA results, with a Prescription Drug User Fee Act goal date of 30 November 2026.

Roche’s giredestrant development programme covers several treatment settings and lines of therapy, as part of its aim to bring new medicines to as many people with HR positive breast cancer as possible.

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Related Topics and Keywords

breast cancer, ER-positive advanced breast cancer, everolimus, Giredestrant, phase III evERA, The New England Journal of Medicine