SHERIDAN, WYOMING - December 2, 2025 - Roche has reported landmark Phase III results for its oral selective estrogen receptor degrader (SERD) giredestrant, positioning the candidate as a potential new standard of care in early-stage ER-positive, HER2-negative breast cancer after a pivotal trial showed superior invasive disease-free survival versus standard endocrine therapy.
First oral SERD to show superior invasive disease-free survival
The Phase III lidERA Breast Cancer study evaluated adjuvant giredestrant against standard-of-care endocrine monotherapy in more than 4,100 patients with medium- or high-risk stage I-III ER-positive, HER2-negative early breast cancer. At a pre-planned interim analysis, the trial met its primary endpoint: giredestrant delivered a statistically significant and clinically meaningful improvement in invasive disease-free survival compared with standard endocrine therapy.
Crucially, lidERA is the first Phase III trial of a SERD to demonstrate a significant benefit in the adjuvant setting, underscoring the molecule's potential to reshape long-term risk management for early-stage patients. Overall survival data are still immature but already show a clear positive trend, supporting the case for regulatory engagement and guideline discussions once full data are available.
Addressing relapse risk and adherence gaps in ER-positive disease
ER-positive breast cancer accounts for roughly 70% of cases worldwide, and the majority of patients are diagnosed at an early stage. Despite advances in endocrine therapy, up to one-third of people eventually experience recurrence on or after adjuvant treatment, and many discontinue therapy early due to safety or tolerability issues, increasing the risk of death.
"Today's results underscore the potential of giredestrant as a new endocrine therapy of choice for people with early-stage breast cancer , where there is a chance for cure,
" said Levi Garraway, MD, PhD, Roche's Chief Medical Officer and Head of Global Product Development. "Given that ER-positive breast cancer accounts for approximately 70% of cases diagnosed,
these findings - together with recent data in the advanced ER-positive setting - suggest that giredestrant has the potential to improve outcomes for many people with this disease.
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By offering an oral, next-generation SERD that both blocks and degrades the estrogen receptor, Roche is aiming to deliver a more effective and better-tolerated option that can support long-term adherence and reduce the risk of invasive recurrence in a large global patient population.
Giredestrant builds momentum with second positive Phase III readout
lidERA is the second major late-stage success for giredestrant in 2025, following the positive evERA Breast Cancer trial presented at the ESMO Congress, which evaluated the agent in combination with everolimus in advanced ER-positive, HER2-negative disease. Together with neoadjuvant data from the coopERA study, where giredestrant outperformed an aromatase inhibitor in lowering Ki67 proliferation levels, the results create a coherent efficacy signal across early, advanced and neoadjuvant settings.
Roche is running a broad clinical development program for giredestrant, spanning multiple lines and disease stages. Ongoing Phase III trials include combinations with CDK4/6 inhibitors in both endocrine-sensitive and endocrine-resistant advanced disease, as well as a study pairing giredestrant with Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer. The overall strategy is to position the SERD as a backbone endocrine agent across the ER-positive continuum.
Safety profile supports adjuvant adoption potential
At the interim analysis, giredestrant was well tolerated, with adverse events consistent with its known safety profile and no unexpected safety signals observed. In the adjuvant setting-where patients may be on therapy for years-tolerability and quality of life are critical to keeping people on treatment long enough to capture the full survival benefit.
With many patients struggling to complete five years of standard endocrine therapy due to side effects, an oral SERD that can maintain or improve efficacy while offering a manageable safety profile could meaningfully improve adherence and long-term outcomes. Regulators and clinicians will be watching the full lidERA dataset closely to understand how giredestrant compares on side-effect burden and discontinuation rates in real-world practice.
Strategic implications for the endocrine therapy landscape
For Roche, lidERA's success reinforces its long-standing leadership in breast cancer while extending its portfolio beyond HER2-targeted franchises into a new generation of ER-directed agents. For oncologists and payers, the data raise important questions about how oral SERDs will be sequenced or substituted for aromatase inhibitors and other endocrine standards in early-stage disease, and how biomarker strategies might evolve as more patients receive SERDs earlier in their treatment journey.
As detailed lidERA results are presented at upcoming medical meetings and shared with health authorities worldwide, giredestrant is poised to become a central topic in guideline discussions and health technology assessments, with the potential to redefine standard adjuvant endocrine therapy for ER-positive, HER2-negative early breast cancer.
For more information about giredestrant, the lidERA Breast Cancer study and Roche's broader breast cancer portfolio, visit https://www.roche.com.