The lidERA Breast Cancer trial is a global Phase III randomized study comparing adjuvant giredestrant—an oral selective estrogen receptor covalent antagonist (SERCA)—against physician's choice of endocrine monotherapy in medium- and high-risk Stage I–III ER+/HER2− early breast cancer. The trial, sponsored by Hoffmann-La Roche, is currently active but no longer enrolling.
Hoffmann-La Roche is conducting the lidERA Breast Cancer trial (NCT04961996), a Phase III, open-label, multicenter, randomized study designed to assess whether adjuvant giredestrant improves outcomes compared with standard physician-selected endocrine monotherapy in patients with ER-positive, HER2-negative early breast cancer at medium or high risk of recurrence (histologically confirmed Stage I–III disease).
Giredestrant is an investigational oral selective estrogen receptor antagonist and degrader that binds covalently to the estrogen receptor, offering a mechanism distinct from traditional selective estrogen receptor modulators (SERMs) such as tamoxifen and aromatase inhibitors. By inducing receptor degradation in addition to antagonism, it may more completely suppress ER-driven transcription—a rationale for its evaluation in the adjuvant setting where residual ER signaling is implicated in late recurrence.
The comparator arm reflects current standard-of-care adjuvant endocrine options, with physician discretion guiding selection; an LHRH agonist is permitted as an adjunct in premenopausal participants. The trial is currently active but no longer recruiting, suggesting primary data collection is underway or nearing completion. Results from lidERA will be pivotal in determining whether giredestrant can improve upon established adjuvant endocrine strategies in this population.
As an open-label design, blinding limitations may influence physician and participant behavior, though this is consistent with pragmatic adjuvant oncology trial methodology. Full efficacy and safety data, including invasive disease-free survival outcomes, have not yet been publicly reported.
Key points
- lidERA is a Phase III, randomized, open-label global trial comparing adjuvant giredestrant to physician's choice of endocrine monotherapy in ER+/HER2− early breast cancer.
- Eligible participants have medium- or high-risk Stage I–III histologically confirmed ER-positive, HER2-negative disease.
- Giredestrant is an investigational oral SERCA (selective estrogen receptor covalent antagonist) with both antagonist and degrader activity against the estrogen receptor.
- LHRH agonist co-administration is permitted, accommodating premenopausal participants in the comparator arm.
- The trial is active but no longer recruiting; efficacy and safety results have not yet been disclosed.
Why it matters
Adjuvant endocrine therapy resistance and late recurrence remain significant challenges in ER+/HER2− early breast cancer; giredestrant's dual mechanism of ER antagonism and degradation positions it as a potentially more potent alternative to current standard agents. Outcomes from lidERA could reshape adjuvant treatment selection for a large proportion of breast cancer diagnoses.