- Giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in ITT and ESR1-mutated populations, respectively, versus standard endocrine therapy plus everolimus1
- By targeting resistance to endocrine treatments, the giredestrant combination seeks to delay disease progression and improve overall patient outcomes1
- The FDA has set a PDUFA goal date for giredestrant in early-stage breast cancer of 30 November 2026 and in advanced disease of 18 December 2026
Basel, 1 October 2026 - Roche (SIX: RO, ROP; OTCQX: RHHBY) announced today that detailed results from the evERA Breast Cancer study, showing investigational giredestrant in combination with everolimus significantly improved progression-free survival (PFS) versus standard endocrine therapy plus everolimus, were published in The New England Journal of Medicine (NEJM). The evERA trial is evaluating giredestrant, an investigational oral selective oestrogen receptor degrader (SERD), in combination with everolimus in people with oestrogen receptor (ER)-positive locally advanced or metastatic breast cancer who had disease progression or recurrence following treatment with a cyclin-dependent kinase (CDK)4/6 inhibitor and endocrine therapy.1
“Despite advancements with CDK4/6 inhibitor treatment in the first-line setting, many people with advanced breast cancer will eventually experience disease progression as their tumours become resistant to endocrine therapy,” said Dr Erica L. Mayer, Medical Oncologist at Dana-Farber Cancer Institute. “The evERA trial demonstrated that the giredestrant combination significantly delayed disease progression, potentially offering a promising all-oral treatment option in a setting where there remains a need for additional treatments to improve patient outcomes.”
In the ESR1-mutated population, the median PFS was 10.0 months with giredestrant plus everolimus compared with 5.5 months in the comparator arm (stratified hazard ratio [HR]=0.38, 95% CI: 0.27-0.54, p<0.001).1 In the intent-to-treat (ITT) population, the median PFS was 8.8 months compared with 5.5 months in the giredestrant and comparator arms, respectively (HR=0.56, 95% CI: 0.44-0.71, p<0.001).1 Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02).1 Follow-up for OS will continue to the next analysis. Adverse events for the giredestrant combination were manageable and consistent with the known safety profiles of the individual medicines.1 No unexpected safety findings were observed, including no photopsia and low rates of bradycardia.1
“The evERA results represent an important step forward for people with ER-positive advanced breast cancer and underscore the potential for giredestrant to help address the challenge of disease progression in this setting,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “Together with the positive phase III lidERA results in early breast cancer, these findings reinforce the potential of giredestrant to redefine care in both metastatic and early disease settings.”
Additional evERA analyses were presented at the 2026 American Society of Clinical Oncology Annual Meeting, showing that giredestrant plus everolimus prolongs PFS2 (time from randomisation to disease progression following second-line therapy) and chemotherapy-free survival compared with standard endocrine therapy, suggesting that the clinical benefit may be sustained beyond initial progression.2
Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer accounts for approximately 70% of breast cancer cases.3 Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes.3,4
evERA was the first positive phase III readout for giredestrant, followed by the lidERA Breast Cancer study in the early-stage setting.1,5 Based on these evERA data, the US Food and Drug Administration (FDA) accepted Roche’s New Drug Application (NDA) for giredestrant in combination with everolimus for the treatment of people with ER-positive, HER2-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease has recurred during or after completing endocrine-based adjuvant therapy, or who have progressed on at least one endocrine-based regimen in the metastatic setting. The FDA is expected to decide on the application by 18 December 2026. The FDA also accepted an NDA under Priority Review for giredestrant as an adjuvant treatment for adults with ER-positive, HER2-negative, stage I, II, and III breast cancer based on the lidERA results. The FDA has set a Prescription Drug User Fee Act goal date of 30 November 2026.
Roche’s expanding giredestrant clinical development programme spans distinct treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with HR-positive breast cancer as possible.
About the evERA Breast Cancer study
evERA Breast Cancer [NCT05306340] is a phase III, randomised, open-label, multicentre study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard endocrine therapy in combination with everolimus in people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase (CDK)4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.6
The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomisation to the time when the disease progresses or a patient dies from any cause.6 In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations.7,8 Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.6
About giredestrant
Giredestrant is an investigational, oral, potent next-generation selective oestrogen receptor degrader and full antagonist.9
Giredestrant is designed to block oestrogen from binding to the oestrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.10
Giredestrant has an extensive clinical development programme including five company-sponsored phase III clinical trials to address the needs of patients acrossmultiple treatment settings and lines of therapy:
- Giredestrant versus standard endocrine therapy as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)11
- Giredestrant plus everolimus versus standard endocrine therapy plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)6
- 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)12
- Giredestrant plus investigator’s choice of a cyclin-dependent kinase (CDK)4/6 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)13
- 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)14
About hormone receptor (HR)-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.15 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.16
HR-positive, human epidermal growth factor receptor 2-negative breast cancer accounts for approximately 70% of breast cancer cases and the majority are diagnosed in the early-stage.3 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to hormones like oestrogen, which can contribute to tumour growth.17
Despite treatment advances, HR-positive breast cancer remains particularly challenging to treat due to its biological complexity.18 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.18,19 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.18,19
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.
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References
[1] Mayer E, et al. Giredestrant plus Everolimus in Advanced Breast Cancer. NEJM; 2026 October. DOI:10.1056/NEJMoa2602457.
[2] Jhaveri K, et al. Post-progression treatment (tx) analyses of evERA Breast Cancer (BC): A phase III trial of giredestrant (GIRE) + everolimus (E) in patients (pts) with estrogen receptor–positive, HER2-negative advanced BC (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i). Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; 2026 May 29 – June 02; Chicago, Illinois, US. #1016.
[3] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696.
[4] Sahin T, et al. Post-progression treatment options after CDK4/6 inhibitors in hormone receptor-positive, HER2-negative metastatic breast cancer. Cancer Treatment Reviews. 2025 April;135:102924.
[5] Bardia A, et al. Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial. Presented at: San Antonio Breast Cancer Symposium (SABCS); 2025 December 9-12; San Antonio, Texas, United States. #GS1-10.
[6] 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 September]. Available from: https://clinicaltrials.gov/study/NCT05306340.
[7] Meisel J L, et al. Real-world estrogen receptor 1 (ESR1) testing patterns and results in U.S. patients with metastatic breast cancer, 2018-2024. JCO Oncol Pract. 2025;21:579.
[8] Chaudhary N, et al. CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. npj Breast Cancer. 2024;10,15.
[9] 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: The ESMO Annual Meeting; 2022 September 9-13; Paris, France. Abstract #211MO.
[10] Metcalfe C, et al. GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes. Presented at: SABCS; 2018 December 4-8; San Antonio, Texas, USA. Abstract #P5-04-07.
[11] 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 September]. Available from: https://clinicaltrials.gov/study/NCT04961996.
[12] 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 September]. Available from: https://clinicaltrials.gov/study/NCT04546009.
[13] 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 September]. Available from: https://clinicaltrials.gov/study/NCT06065748.
[14] 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 September]. Available from: https://clinicaltrials.gov/study/NCT05296798.
[15] World Health Organization. Breast Cancer [Internet; cited 2026 September]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer.
[16] World Health Organization. Cancer Today [Internet; cited 2026 September]. Available from: https://gco.iarc.fr/today/en/dataviz/bars?mode=cancer&types=1&group_populations=1&sexes=2&key=asr&age_end=14.
[17] National Cancer Institute. Hormone Therapy for Breast Cancer [Internet; cited 2026 September]. Available from: https://www.cancer.gov/types/breast/breast-hormone-therapy-fact-sheet.
[18] Hanker A, et al. Overcoming Endocrine Resistance in Breast Cancer. Canc Cell. 2020 Apr 13;37(4):496–513.
[19] Başaran G, et al. Ongoing unmet needs in treating estrogen receptor-positive/HER2-negative metastatic breast cancer. Cancer Treat Rev. 2018 Feb;63:144-55.
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