Positive phase III results show Roche’s giredestrant significantly improved progression-free survival in ER-positive advanced breast cancer
Roche (OTCQX: RHHBY) announced positive Phase III results from the evERA study evaluating giredestrant plus everolimus in ER-positive, HER2-negative advanced breast cancer patients previously treated with CDK4/6 inhibitor and endocrine therapy.
The trial met both co-primary endpoints, showing statistically significant and clinically meaningful improvement in progression-free survival in both intention-to-treat and ESR1-mutated populations compared to standard-of-care plus everolimus. While overall survival data were immature, a clear positive trend was observed.
This marks the first positive head-to-head phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus standard of care. The combination was well-tolerated with no new safety signals observed.
Roche (OTCQX: RHHBY) ha annunciato risultati positivi di fase III dallo studio evERA che valuta giredestrant più everolimus in pazienti con cancro al seno avanzato ER‑positivo/HER2‑negativo, precedentemente trattati con inibitore CDK4/6 e terapia endocrina.
Lo studio ha raggiunto entrambi gli endpoint co-primari, mostrando un miglioramento statisticamente significativo e clinicamente rilevante della sopravvivenza libera da progressione sia nella popolazione intent-to-treat sia in quella con mutazione ESR1 rispetto alla terapia standard più everolimus. Sebbene i dati sulla sopravvivenza globale siano ancora maturi, si è osservata una chiara tendenza positiva.
Questo segna il primo trial di fase III head-to-head positivo che confronta un regime contenente un degrador dell’estrogeno interamente orale con la terapia standard. La combinazione è stata ben tollerata, senza nuove segnalazioni di sicurezza osservate.
Roche (OTCQX: RHHBY) anunció resultados positivos de fase III del estudio evERA, que evalúa giredestrant más everolimus en pacientes con cáncer de mama avanzado ER‑positivo/HER2‑negativo previamente tratados con inhibidores de CDK4/6 y terapia endocrina.
El ensayo cumplió con ambos endpoints co-primarios, mostrando una mejora estadísticamente significativa y clínicamente relevante en la supervivencia libre de progresión tanto en la población de intención de tratar como en la de ESR1 mutante en comparación con la atención habitual más everolimus. Aunque los datos de supervivencia global están aún inmaduros, se observó una clara tendencia positiva.
Este hito marca el primer ensayo de fase III head-to-head positivo que investiga un régimen que contiene un degrador del receptor de estrógeno completamente oral frente a la atención estándar. La combinación se toleró bien y no se observaron nuevos señales de seguridad.
로체(Roche, OTCQX: RHHBY)가 giredestrant plus everolimus를 평가하는 evERA 연구의 3상 양성 결과를 발표했습니다. 이는 CDK4/6 억제제와 내분비 치료를 이전에 받은 ER‑양성/HER2‑음성 진행성 유방암 환자를 대상으로 합니다.
이 연구는 두 가지 공설적 주요 지표를 모두 충족했고, 사고진행 없이 생존(PFS)에서 통계적으로 의미 있고 임상적으로도 유의미한 개선을 ITT 집단과 ESR1 변이 집단 모두에서 표준 치료+에버로몰리스 대비 보였습니다. 전반 생존(OS) 데이터는 아직 미숙하지만 긍정적 경향이 관찰되었습니다.
이는 동일한 경구형 선택적 에스트로겐 수용체 분해제(SERD) 포함 요법과 표준 치료를 직접 비교한 최초의 긍정적인 3상 헤드-투-헤드 연구가 되는 기록입니다. 이 조합은 내약성이 양호했고 새로운 안전 신호는 관찰되지 않았습니다.
Roche (OTCQX: RHHBY) a annoncé des résultats positifs de phase III de l’essai evERA évaluant giredestrant plus everolimus chez des patientes atteintes d’un cancer du sein avancé ER‑positif/HER2‑négatif, préalablement traitées par inhibiteurs CDK4/6 et thérapie endocrinienne.
L’essai a atteint les deux critères co-primaires, montrant une amélioration statistiquement significative et cliniquement pertinente de la survie sans progression dans les populations ITT et ESR1-muté par rapport à la prise en charge standard plus everolimus. Bien que les données de survie globale soient immature, une tendance positive a été observée.
Cela marque le premier essai de phase III en tête-à-tête positif évaluant un régime contenant un dégradateur du récepteur des œstrogènes entièrement oral par rapport aux soins standards. Cette combinaison a été bien tolérée et aucune nouvelle signalisation de sécurité n’a été observée.
Roche (OTCQX: RHHBY) hat positive Phase-III-Ergebnisse der evERA-Studie bekannt gegeben, die Giredestrant plus Everolimus bei ER-positiven, HER2-negativen fortgeschrittenen Brustkrebspatientinnen bewertet, die zuvor mit CDK4/6-Inhibitoren und endokriner Therapie behandelt wurden.
Die Studie erreichte beide Co-Primärendpunkte und zeigte eine statistisch signifikante und klinisch bedeutsame Verbesserung des progressionsfreien Überlebens sowohl in der Intention-to-Treat- als auch in der ESR1-Mutant-Population im Vergleich zur Standardtherapie plus Everolimus. Während die Gesamtüberlebensdaten noch unausgereift sind, wurde ein deutlicher positiver Trend beobachtet.
Dies markiert die erste positive Head-to-Head-Phase-III-Studie, die ein ausschließlich orales Regime mit einem Selektiven Östrogenrezeptor-Degrader (SERD) gegenüber der Standardbehandlung untersucht. Die Kombination wurde gut vertragen, es wurden keine neuen Sicherheitssignale beobachtet.
روش (OTCQX: RHHBY) أعلن عن نتائج إيجابية من المرحلة الثالثة لدراسة evERA التي تقيم جيريداسترانت مع إيفروليموس لدى مرضى سرطان الثدي المتقدم الإيجابي للهرمون المستهدف ER وAlHER2‑Neg، والذين تلقوا علاجاً مضاداً لـ CDK4/6 والعلاج الهرموني سابقاً.
حققت الدراسة كلا النقطتين الرئيسيتين المشتركتين، حيث أظهرت تحسناً ذا دلالة إحصائية وذو معنى سريري في البقاء خالٍ من تقدم المرض في كل من مجموعة النية في المعالجة ومجموعة ESR1‑متحورة مقارنةً بالرعاية القياسية مع Everolimus. بينما البيانات الخاصة بالبقاء على قيد الحياة الإجمالي لم تكن ناضجة، لوحظ اتجاه إيجابي واضح.
هذه هي أول تجربة من المرحلة الثالثة تقارن مباشرة بين نظام بروتيني فموي مضاد لمستقبِلات الإستروجين مع النظام القياسي. التوليفة استُقبلت جيداً ولم تَرُصد إشارات سلامة جديدة.
罗氏药业 (OTCQX: RHHBY) 公布了 evERA 研究的 III 期积极结果，该研究评估 吉雷德斯特兰特（giredestrant）+埃弗洛莫司（everolimus）在 ER 阳性、HER2 阴性且既往接受过 CDK4/6 抑制剂和内分泌治疗的晚期乳腺癌患者中的效果。
该试验达到两个共-primary 终点，显示在意向性治疗（ITT）人群和 ESR1 突变人群中，与标准治疗+ everolimus 相比，无进展生存期（PFS）有统计学显著且临床意义的改善。尽管总体生存数据尚不成熟，但观察到明确的积极趋势。
这是首个正向的直接对比 III 期头对头研究，比较含有全口服的选择性雌激素受体降解剂（SERD）方案与标准治疗。该联合方案耐受性良好，未观察到新的安全信号。
- First positive head-to-head Phase III trial for all-oral selective oestrogen receptor degrader combination
- Statistically significant improvement in progression-free survival for both patient populations
- Positive trend observed in overall survival data
- Well-tolerated safety profile with no new safety signals
- All-oral combination potentially reducing treatment burden on patients
- Overall survival data still immature and requires further follow-up
- Regulatory approval still pending
- evERA met its co-primary endpoints; giredestrant plus everolimus demonstrated significant benefit in ITT and ESR1-mutated populations in post-CDK inhibitor setting, compared with standard of care plus everolimus
- The all-oral combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments; no new safety signals were observed
- evERA is the first positive head-to-head phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus a standard of care combination1
- Data will be presented at an upcoming medical meeting and shared with health authorities
Basel, 22 September 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive results from the phase III evERA study evaluating investigational giredestrant in combination with everolimus in people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer previously treated with cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. The study met both co-primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the intention-to-treat and ESR1-mutated populations, compared with standard-of-care endocrine therapy plus everolimus. Overall survival (OS) data were immature, but a clear positive trend was observed. Follow-up continues to the next OS analysis. The giredestrant combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments, and no new safety signals were observed. This is the first positive head-to-head phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus a standard of care combination.1
“These results show that the giredestrant combination provided a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development. “We look forward to discussing these results with regulatory authorities with the goal of making this giredestrant-based regimen available to many people with advanced ER-positive breast cancer.”
ER-positive breast cancer accounts for approximately
Our extensive giredestrant clinical development programme spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.
Data from the evERA study will be submitted to health authorities with the view of bringing this potential treatment option to patients as soon 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-of-care endocrine therapy in combination with everolimus in people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.1
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. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to
About giredestrant
Giredestrant is an investigational, oral, next-generation selective oestrogen receptor degrader (SERD) and full antagonist.6
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.7,10-12
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 ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)13
- Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)1
- 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)14
- Giredestrant plus investigator’s choice of a cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor versus fulvestrant plus a CDK 4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)15
- 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)16
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.17 Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.18
ER-positive breast cancer accounts for approximately
Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity.3 Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy.3,20 There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.3,20
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
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045.
Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.
References
[1] 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 2025 September]. Available from: https://clinicaltrials.gov/study/NCT05306340.
[2] Kinslow C, et al. Prevalence of Estrogen Receptor Alpha (ESR1) Somatic Mutations in Breast Cancer. JNCI Cancer Spectrum; 2022 Oct;6(5):pkac060.
[3] Hanker A, et al. Overcoming Endocrine Resistance in Breast Cancer. Canc Cell. 2020 Apr 13;37(4):496–513.
[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] Wood L. A review on adherence management in patients on oral cancer therapies. Eur J Oncol Nurs. 2012 Sept; 16(4):432-38.
[6] Lloyd M, et al. Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role. Ther Adv Med Oncol. 2022 Jul 30;14:17588359221113694.
[7] Metcalfe C, et al. GDC-9545: A novel ER antagonist and clinical candidate that combines desirable mechanistic and pre-clinical DMPK attributes. Presented at: San Antonio Breast Cancer Symposium; 2018 December 4-8; San Antonio, Texas, USA. Abstract #P5-04-07.
[8] Liang J, et al. GDC-9545 (giredestrant): A potent and orally bioavailable selective estrogen receptor antagonist and degrader with an exceptional preclinical profile for ER+ breast cancer. J Med Chem. 2021;64(16):11841-56.
[9] Jhaveri K, et al. A first-in-human phase I study to evaluate the oral selective estrogen receptor degrader (SERD), GDC-9545, in postmenopausal women with estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer. Presented at: San Antonio Breast Cancer Symposium; 2019 December 10-14; San Antonio, Texas, USA. Abstract #PD7-05.
[10] 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 European Society for Medical Oncology Annual Meeting; 2022 September 9-13; Paris, France. Abstract #211MO.
[11] Hurvitz SA, et al. Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2023;24:1029-41.
[12] Hershman D, et al. Effect of early discontinuation and nonadherence to adjuvant hormone therapy on mortality in women with breast cancer. J Clin Oncol. 2010 May 20;28(15).
[13] 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 2025 September]. Available from: https://clinicaltrials.gov/study/NCT04961996.
[14] 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 2025 September]. Available from: https://clinicaltrials.gov/study/NCT04546009.
[15] 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 2025 September]. Available from: https://clinicaltrials.gov/study/NCT06065748.
[16] 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 2025 September]. Available from: https://clinicaltrials.gov/study/NCT05296798.
[17] World Health Organisation. Breast Cancer [Internet; cited 2025 September]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer.
[18] International Agency for Research on Cancer. Breast cancer cases and deaths are projected to rise globally [Internet; cited 2025 September]. Available from: https://www.iarc.who.int/wp-content/uploads/2025/02/pr361_E.pdf.
[19] National Cancer Institute. Hormone Therapy for Breast Cancer [Internet; cited 2025 September]. Available from: https://www.cancer.gov/types/breast/breast-hormone-therapy-fact-sheet.
[20] 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.
Roche Global Media Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche.com
| Hans Trees, PhD Phone: +41 79 407 72 58 | Sileia Urech Phone: +41 79 935 81 48 |
| Nathalie Altermatt Phone: +41 79 771 05 25 | Lorena Corfas Phone: +41 79 568 24 95 |
| Simon Goldsborough Phone: +44 797 32 72 915 | Karsten Kleine Phone: +41 79 461 86 83 |
| Kirti Pandey Phone: +49 172 6367262 | Yvette Petillon Phone: +41 79 961 92 50 |
| Dr Rebekka Schnell Phone: +41 79 205 27 03 |
Roche Investor Relations
| Dr Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com | Dr Sabine Borngräber Phone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com |
| Dr Birgit Masjost Phone: +41 61 68-84814 e-mail: birgit.masjost@roche.com |
Investor Relations North America
| Loren Kalm Phone: +1 650 225 3217 e-mail: kalm.loren@gene.com |
Attachment
FAQ
What were the main results of Roche's Phase III evERA trial for giredestrant?
How does RHHBY's giredestrant combination differ from current breast cancer treatments?
What type of breast cancer patients were included in Roche's evERA study?
What was the safety profile of Roche's giredestrant combination therapy?
When will Roche's giredestrant be available for breast cancer patients?
