Oral selective estrogen receptor degraders in ER+/HER2− breast cancer: a systematic review with pooled analysis of metastatic randomized trials and narrative synthesis of adjuvant evidence
- Study type
- Meta-analysis
- Design
- Systematic review registered in PROSPERO (CRD420261358420), with random-effects meta-analysis of metastatic trials and narrative review of adjuvant evidence
- Sample size
- 10 randomised trials (one adjuvant trial with 4,170 patients and nine metastatic trials); pooled analysis of six monotherapy trials with 2,502 patients
- Source
- Front. Oncol. · 2026
In plain words
This study brought together the results of several studies of tablets that break down the oestrogen receptor in breast cancer cells (oral SERDs). In advanced breast cancer, these medicines kept the disease from progressing for longer, especially in patients whose tumour has an ESR1 mutation. In one of the studies, the drug giredestrant also lowered the risk of the cancer coming back or of a new invasive cancer in patients with early breast cancer. Decisions about using these medicines should be made with your treating doctor.
Key results
Treatment arms and regimens
One of giredestrant, imlunestrant, elacestrant, camizestrant, vepdegestrant (a PROTAC) or amcenestrant. Dose details in the full text of the paper.
Standard endocrine therapy in the control arm of each trial. Dose details in the full text of the paper.
Source of the regimen details: Abstract of the paper (doses are not stated in the abstract; dose details in the full text of the paper)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Randomised phase 2 and 3 trials comparing oral selective oestrogen receptor degraders (SERDs) with standard endocrine therapy in ER-positive, HER2-negative breast cancer. PubMed, Cochrane CENTRAL and conference abstract archives (SABCS, ESMO, ASCO) were searched for 2020 to 2026.
Endpoints
In metastatic disease, hazard ratios (HR) for progression-free survival (PFS) were pooled with a random-effects model. In the adjuvant setting, the main outcome was invasive disease-free survival (iDFS) in the lidERA trial. Prespecified sensitivity analyses included a Bayesian reanalysis.
Safety and side effects
Adverse event information is not reported in the abstract; for safety data see the full text of the paper and the original trials.
Clinical significance and place in guidelines
This review shows that oral SERDs give a consistent PFS benefit in ER-positive, HER2-negative metastatic breast cancer, with the strongest effect in ESR1-mutated tumours. The positive lidERA result for giredestrant in the adjuvant setting also points to a potential new standard of care. The authors present the review as a framework for clinical decision-making. The status of drug approvals and formal clinical guideline recommendations should be checked separately, as the abstract does not address them.
Limitations
The power of Egger's test for publication bias was limited by the small number of trials (k = 6). In early disease only one trial (lidERA) was included and it was reviewed narratively rather than quantitatively pooled. Moderate heterogeneity (I² = 35.2%) was present in the overall PFS analysis. The abstract provides no data on adverse events or overall survival.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.