Roche Advances Giredestrant Toward Possible New Standard of Care in ER-Positive Early-Stage Breast Cancer

Roche Advances Giredestrant Toward Possible New Standard of Care in ER-Positive Early-Stage Breast Cancer

(IN BRIEF) Roche has received FDA acceptance under Priority Review for its New Drug Application for giredestrant as an adjuvant treatment for adults with ER-positive, HER2-negative stage I-III breast cancer. The FDA is expected to decide on the application by 30 November 2026. The filing is supported by phase III lidERA Breast Cancer study results showing that giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with standard-of-care endocrine therapy. At three years, 92.4% of patients receiving giredestrant were alive and free from invasive disease, compared with 89.6% of patients on standard endocrine therapy. The therapy was also well tolerated, with a lower discontinuation rate than standard treatment. Roche sees giredestrant as a potential new standard of care in early-stage ER-positive breast cancer, where most patients are diagnosed and where preventing recurrence is especially important. The medicine is also being studied in several other phase III trials across early-stage, locally advanced and metastatic breast cancer settings.

(PRESS RELEASE) BASEL, 2-Jun-2026 — /EuropaWire/ — Roche has announced that the U.S. Food and Drug Administration has accepted its New Drug Application for giredestrant under Priority Review, marking an important regulatory step for the investigational oral therapy in early-stage breast cancer. The application covers giredestrant as an adjuvant treatment for adults with oestrogen receptor-positive, HER2-negative stage I, II and III breast cancer, a setting where treatment is intended to reduce the risk of disease returning after initial therapy. The FDA has set a Prescription Drug User Fee Act decision date of 30 November 2026.

Giredestrant is an investigational oral selective oestrogen receptor degrader, or SERD, designed to block oestrogen activity by targeting the oestrogen receptor for degradation. By preventing oestrogen from binding to the receptor and promoting receptor breakdown, the therapy is intended to stop or slow the growth of cancer cells driven by oestrogen signalling.

The FDA’s acceptance is based on results from the phase III lidERA Breast Cancer study, which evaluated adjuvant giredestrant against standard-of-care endocrine therapy in people with medium- or high-risk ER-positive, HER2-negative early-stage breast cancer. The study enrolled more than 4,100 patients and showed that giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with standard endocrine therapy. The result was measured through invasive disease-free survival, with a hazard ratio of 0.70 and a statistically significant p-value of 0.0014.

At the three-year mark, 92.4% of patients treated with giredestrant were alive and free from invasive disease, compared with 89.6% of those receiving standard-of-care endocrine therapy. The benefit was observed across clinically relevant patient subgroups. Overall survival data were still immature at the time of analysis, although a positive trend was reported, with further follow-up planned.

Roche said giredestrant was well tolerated in the study, with adverse events described as manageable and consistent with the medicine’s known safety profile. Treatment discontinuation was lower in the giredestrant arm, at 5.3%, compared with 8.2% among patients receiving standard endocrine therapy.

Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, said giredestrant could represent the first major advance in endocrine therapy for early-stage ER-positive breast cancer in decades. He noted that the FDA’s filing acceptance brings Roche closer to potentially introducing a new standard of care for patients diagnosed at an earlier stage, when the opportunity for cure is greatest.

The regulatory milestone follows additional giredestrant data presented at the 2026 American Society of Clinical Oncology Congress. Roche said the expanding evidence base continues to support the medicine’s clinical benefit profile across ER-positive breast cancer, including both early-stage and advanced disease.

The company is also pursuing giredestrant in advanced breast cancer. The FDA recently accepted a separate application for giredestrant in combination with everolimus for patients with ESR1-mutated, ER-positive advanced breast cancer, based on results from the evERA study. A decision for that application is expected in December 2026.

Breast cancer remains one of the world’s most common and deadly cancers. Globally, around 2.3 million people are diagnosed with the disease each year. ER-positive breast cancer accounts for approximately 70% of all breast cancer cases, and most of these cases are detected at an early stage. However, recurrence remains a major challenge, with up to one-third of patients eventually experiencing disease recurrence on or after adjuvant endocrine therapy. Treatment interruptions and early discontinuation caused by safety or tolerability challenges can also increase the risk of poorer outcomes.

About the lidERA Breast Cancer study
lidERA Breast Cancer [NCT04961996] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of adjuvant giredestrant versus standard-of-care endocrine therapy in people with medium- or high-risk stage I-III oestrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.15 Over 4,100 patients were enrolled in the study.15

The primary endpoint is invasive disease-free survival (iDFS) excluding unrelated cancers in other organs (second primary non-breast cancers).15 Key secondary endpoints include overall survival, iDFS including second primary non-breast cancers, disease-free survival and safety.15

About giredestrant
Giredestrant is an investigational, oral, potent next-generation selective oestrogen receptor degrader and full antagonist.16

Giredestrant is designed to block oestrogen from binding to the oestrogen receptor, triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.17

Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

• Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)15
• Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)18
• Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)19
• Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)20
• Giredestrant plus Phesgo® (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)21

About oestrogen receptor (ER)-positive breast cancer
Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year.8 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.22

ER-positive breast cancer accounts for approximately 70% of breast cancer cases, and the majority are diagnosed in the early-stage.9 A defining feature of ER-positive breast cancer is that its tumour cells have receptors that attach to oestrogen, which can contribute to tumour growth.23

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.24 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.24, 25 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.24, 25

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years, and it continues to be a major focus of research and development. Our legacy began with the development of the first targeted therapy for human epidermal growth factor receptor 2-positive breast cancer, and we continue to push the boundaries of science to address the complexities of all breast cancer subtypes.

By leveraging our dual expertise in pharmaceuticals and diagnostics, we are dedicated to providing tailored treatment approaches and improving outcomes for every patient, from early to advanced stages of the disease. Together with our partners, we are relentlessly pursuing a cure, as we strive for a future where no one dies from breast cancer.

About Roche
Roche (SIX: RO, ROP; OTCQX: RHHBY) is a healthcare company uniquely placed to prevent, stop and cure diseases by uniting leading science and technology across diagnostics, medicines and digital solutions.

Roche was founded in Basel, Switzerland in 1896 and today is a leading provider of transformative medicines and diagnostics for millions of people in over 150 countries around the world. It is dedicated to tackling healthcare challenges that place the greatest strain on patients, families, communities and healthcare systems. Across its Diagnostics and Pharmaceutical divisions, Roche focuses on areas including oncology, neurology, cardiovascular and metabolic diseases, ophthalmology, infectious diseases and immunology with the aim of providing real and positive change for patients, the people they love and the professionals who care for them.

Genentech in the United States is a fully owned subsidiary in the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, a major innovator in the Japanese therapeutic antibody market.

For more information, please visit www.roche.com.

All trademarks used or mentioned in this release are protected by law.

References
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[15] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician’s Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2- Negative Early Breast Cancer (lidERA Breast Cancer) [Internet; cited 2026 June]. Available from: https://clinicaltrials.gov/study/NCT04961996
[16] Martin M, et al. Giredestrant (GDC-9545) vs physician choice of endocrine monotherapy (PCET) in patients (pts) with ER+, HER2– locally advanced/metastatic breast cancer (LA/mBC): Primary analysis of the phase 2, randomised, open-label acelERA BC study. Presented at: ESMO Annual Meeting; 2022 September 9-13; Paris, France. Abstract #211MO.
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[18] ClinicalTrials.gov. A 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) [Internet; cited 2026 June]. Available from: https://clinicaltrials.gov/study/NCT05306340
[19] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2- Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer) [Internet; cited 2026 June]. Available from: https://clinicaltrials.gov/study/NCT04546009
[20] ClinicalTrials.gov. A Study to Evaluate Efficacy and Safety of Giredestrant Compared With Fulvestrant (Plus a CDK4/ 6 Inhibitor), in Participants With ER-Positive, HER2-Negative Advanced Breast Cancer Resistant to Adjuvant Endocrine Therapy (pionERA Breast Cancer) [Internet; cited 2026 June]. Available from: https://clinicaltrials.gov/study/NCT06065748
[21] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer) [Internet; cited 2026 June]. Available from: https://clinicaltrials.gov/study/NCT05296798.
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[25] Başaran G, et al. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer. Cancer Treat Rev. 2018;63:144-55.

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