The news at a glance
- This study was in women with advanced hormone-positive breast cancer whose disease had grown after tablets such as ribociclib or palbociclib [1].
- A new anti-hormone tablet (giredestrant) plus everolimus tablets was compared with usual hormone treatment plus everolimus [1].
- When the tumour had an ESR1 genetic change, the disease was kept under control almost twice as long [1].
- Across all patients the result was also better, and side effects were similar in the two groups; this new tablet is not yet approved [1].
- Overall survival: how long patients lived.
- Progression-free survival: how long the disease did not get worse.
- Disease-free or event-free survival: how long the disease did not come back after treatment.
- Median: the number that half of patients were above and half below; for example, "a median of 10 months" means that in half of patients the disease stayed under control for at least 10 months.
- Phase 3: a large, careful study comparing a new drug with the usual treatment; the basis of most approvals.
Talk to your doctor about what this result means for you.
What was reported?
For physicians
Hormone receptor-positive (ER-positive), HER2-negative breast cancer is the most common type of breast cancer. First-line treatment of advanced disease is usually endocrine therapy plus a CDK4/6 inhibitor, and after progression the options become more limited. Everolimus plus exemestane has been one of these options since 2012 and the BOLERO-2 trial [2]. ESR1 mutations, which often emerge after endocrine therapy, cause resistance to some endocrine drugs, and new oral SERDs have been designed to overcome this resistance [3, 4].
In the open-label phase 3 evERA trial, patients were randomised 1:1 to giredestrant + everolimus (both oral; 183 patients) or standard endocrine therapy (exemestane, fulvestrant or tamoxifen) + everolimus (190 patients) [1]. The primary endpoint was assessed first in patients with ESR1 mutations and then in all patients [1].
In 207 patients with ESR1 mutations, median progression-free survival was 10.0 months with giredestrant + everolimus and 5.5 months with standard therapy + everolimus. In the overall population, the figures were 8.8 and 5.5 months [1].
What does this finding mean for patients?
If you have advanced hormone-positive breast cancer and the disease has grown after treatment with drugs such as ribociclib, palbociclib or abemaciclib (CDK4/6 inhibitors), this study offers a fully oral option that clearly delayed the disease getting worse, especially in tumours with an ESR1 mutation [1]. An ESR1 mutation can be checked with a blood test (liquid biopsy) or on tumour tissue. Giredestrant is not yet an approved drug; mouth sores (stomatitis) are a common side effect of everolimus, and you should talk to your doctor about how to prevent them [1].
Trial details and regimen (for physicians)
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- Population: ER-positive/HER2-negative locally advanced or metastatic breast cancer with progression or recurrence after a CDK4/6 inhibitor + endocrine therapy; primary endpoint investigator-assessed progression-free survival, in the ESR1-mutated population and then in the overall population [1].
- Adverse events occurred in 98.9% vs 96.8%; the most common were stomatitis (47.3% vs 48.9%), diarrhoea (26.9% vs 22.6%) and anaemia (23.6% vs 21.0%) [1].
- The benefit in the overall population comes mainly from the ESR1-mutated subgroup; assessing ESR1 mutation status before choosing second-line therapy is reasonable [1, 4].
- By comparison, in EMBER-3 imlunestrant monotherapy improved progression-free survival only in ESR1-mutated patients, and imlunestrant + abemaciclib was effective in all patients [3]. A systematic review with pooled analysis showed a consistent benefit of oral SERDs, especially in ESR1-mutated tumours [4].
evERA trial regimen (investigational; giredestrant not yet approved)
Giredestrant + everolimus
Advanced ER-positive/HER2-negative breast cancer after a CDK4/6 inhibitor + endocrine therapyEach drug’s schedule in the table
Advanced ER-positive/HER2-negative breast cancer after a CDK4/6 inhibitor + endocrine therapy
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Giredestrant | 30 mg | Oral | Once daily, days 1 to 28, every 28 days |
| Everolimus | 10 mg | Oral | Once daily |
| Pre- or perimenopausal women and men | |||
| LHRH agonist | Per label | Injection | Day 1, every 28 days |
Comparator arm: exemestane 25 mg daily, fulvestrant 500 mg intramuscularly (days 1 and 15 of cycle 1, then day 1 of each cycle) or tamoxifen 20 mg daily, with everolimus 10 mg. Stomatitis prevention: an alcohol-free dexamethasone mouthwash (0.5 mg in 5 mL) four times a day for 8 weeks from the start of treatment was strongly recommended. As in the registered protocol [5, 1].
Evidence: evERA Breast Cancer (2026)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Approval status, limitations and next steps
- Not yet approved: giredestrant is an investigational drug. According to the manufacturer, the FDA has accepted its application for approval with everolimus for ESR1-mutated tumours after a CDK4/6 inhibitor, and a decision is expected by December 2026 (company announcement).
- The study was open-label and the primary endpoint was investigator-assessed; overall survival data have not yet been reported [1].
- The comparator arm was standard endocrine therapy + everolimus, not other new options such as PI3K/AKT pathway targeted drugs or other SERDs [1].
Giredestrant has also been studied after surgery: in one study it lowered the chance of early breast cancer coming back [4]; once the full results are published, the drug may be used more widely.
Main study
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Key study
1 itemGiredestrant plus Everolimus in Advanced Breast Cancer
References
5 referencesShow all references, 4 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1
- 2Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
- 3Imlunestrant with or without Abemaciclib in Advanced Breast Cancer
- 4
- 5A 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) (NCT05306340)
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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