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2025 San Antonio Breast Cancer Symposium: Selective Estrogen Degrader Giredestrant Improves on Standard Endocrine Therapy for Patients with ER-positive, HER2-negative Early Breast Cancer: Phase III lidERA Breast Cancer trial Findings
An interview with: Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration, University of California, Los Angeles and Jonsson Comprehensive Cancer Center, Los Angeles, California USA.
SAN ANTONIO, USA—Significant and clinically meaningful improvements in disease-free survival were reported from the Phase III lidERA Breast Cancer trial at the 2025 San Antonio Breast Cancer Symposium, in San Antonio, USA. First author of the study, Aditya Bardia MD MPH, Professor of Medicine and Director of Translational Research Integration at University of California, Los Angeles and the Jonsson Comprehensive Cancer Center, in Los Angeles, California, met up with Audio Journal Oncology reporter, Peter Goodwin.
Audio Journal of Oncology with: Aditya Bardia MD MPH
IN “[GOODWIN] I am at the San Antonio ……. OUT: …….of Oncology. I’m Peter Goodwin” 7:42 secs
San Antonio Breast Cancer Symposium ABSTRACT: GS1-10
“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
Speaker:
Aditya Bardia, University of California Los Angeles, Los Angeles, CA
Authors:
Bardia1, P. Schmid2, M. Martín3, S. Hurvitz4, K. Jung5, M. Rimawi6, S. Saji7, G. Werutsky8, N. Harbeck9, S. Loi10, A. Ogiya11, M. Ruiz-Borrego12, A. Alacacıoğlu13, J. Wu14, C. Ye15, M. Liste-Hermoso16, N. Withana16, T. Badovinac Crnjevic17, M. Shah18, P. Pérez-Moreno19, C. Geyer, Jr.20; 1University of California Los Angeles, Los Angeles, CA, 2Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UNITED KINGDOM, 3Universidad Complutense, GEICAM, CIBERONC, Madrid, SPAIN, 4Department of Medicine, UW Medicine, Fred Hutchinson Cancer Center, Seattle, WA, 5Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA, REPUBLIC OF, 6Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 7Department of Medical Oncology, Fukushima Medical University, Fukushima, JAPAN, 8Breast Cancer Program, Latin American Cooperative Oncology Group and Centro de Pesquisa em Oncologia, Hospital Sao Lucas PUCRS, Porto Alegre, JAPAN, 9Department of Obstetrics and Gynecology, LMU University Hospital, Munich, GERMANY, 10Division of Cancer Research, Peter MacCallum Cancer Centre and The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, AUSTRALIA, 11Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, JAPAN, 12Breast Cancer Unit, Hospital Universitario Virgen del Rocío, Sevilla, SPAIN, 13Department of Oncology, İzmir Kâtip Çelebi University, Atatürk Training and Research Hospital, İzmir, TURKEY, 14Department of Breast Surgery, Cancer Hospital/Institute, Fudan University, Shanghai, CHINA, 15Department of Oncology Biostatistics, Genentech, Inc., South San Francisco, CA, 16Global Product Development – Clinical Science Oncology (PDOH), F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 17PDO – Clinical Science Oncology, F. Hoffmann-La Roche Ltd, Basel, SWITZERLAND, 18Product Development Safety, Genentech, Inc., South San Francisco, CA, 19Product Development Oncology/Hematology (PDOH), Genentech, Inc., South San Francisco, CA, 20Department of Medicine, University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center, Pittsburgh, PA.
Background:
Adjuvant (adj) endocrine therapy (ET) is the mainstay treatment (tx) for estrogen receptor-positive, HER2-negative early breast cancer (ER+ HER2- eBC). However, up to 1/3 of patients (pts) eventually experience recurrence. Clinically, there is an unmet need for more tolerable and efficacious ET to improve adherence and pt outcomes. Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs (Liang 2021; Bardia 2023) and demonstrated superior antiproliferative activity vs anastrozole in the neoadj coopERA BC trial (Hurvitz 2023). Results of the prespecified interim analysis of the global, randomized lidERA BC trial (NCT04961996) are presented.
Methods: Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr). The primary endpoint was invasive disease-free survival (IDFS). Key secondary endpoints were overall survival (OS), distant recurrence-free interval (DRFI), and safety.
Results: 4170 pts were randomized (Aug 2021-Sep 2023): 2084 to giredestrant; 2086 to standard-of-care ET. Median age was 54.0 yr; 59.3% of pts were postmenopausal; 13.0%, 47.4%, and 39.6% had Stage I, II, and III BC, respectively. Median follow-up at clinical cutoff (Aug 8, 2025) was 32.3 months, with 336 IDFS events. Efficacy is shown in the table. Giredestrant demonstrated superior IDFS vs standard-of-care ET (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.57, 0.87; p = 0.0014). 3-yr IDFS rates were 92.4% and 89.6%, respectively. There was a trend towards OS improvement in the giredestrant arm vs the standard-of-care ET arm (HR 0.79; 95% CI, 0.56,1.12). The DRFI HR was 0.69 (95% CI, 0.54, 0.89). The most common adverse events (AEs) in the giredestrant vs standard-of-care ET arms, respectively, were arthralgia (48.0% vs 47.1%), hot flush (27.4% vs 28.8%), and headache (15.3% vs 13.2%); the most common Grade 3-4 AEs, hypertension (2.6% vs 2.0%) and arthralgia (1.5% vs 1.8%). Discontinuations due to AEs occurred in 5.3% with giredestrant vs 8.2% with standard-of-care ET.
Conclusions: lidERA BC is the first Phase III trial to demonstrate benefit with an oral SERD in eBC. Giredestrant tx resulted in a statistically significant and clinically meaningful IDFS improvement vs standard-of-care ET in ER+, HER2- eBC. OS trended in favor of the giredestrant arm, and DRFI was improved vs standard-of-care ET. The safety profile was favorable and consistent with known profiles, and the discontinuation rate was slightly lower with giredestrant compared with standard-of-care ET. Overall, the results support giredestrant as a potential new standard for pts with HR+ eBC.
PRESS RELEASE:
Novel Endocrine Therapy Giredestrant Improves Disease-free Survival Over Standard of Care for Patients With Early-stage Breast Cancer in Phase III lidERA Trial
SAN ANTONIO – The investigational, oral selective estrogen receptor degrader (SERD) giredestrant given as an adjuvant therapy showed significant improvement in invasive disease-free survival (iDFS) compared with the current standard-of-care endocrine therapy in patients with early-stage, hormone receptor (HR)-positive, HER2-negative breast cancer, according to the results of the phase III IidERA trial presented at the San Antonio Breast Cancer Symposium (SABCS), held December 9-12, 2025.
“For patients with HR-positive breast cancer—which accounts for about 70% of breast cancer cases— effective adjuvant therapy at the early stage offers a real opportunity to eradicate micrometastatic disease and improve survival in the curative setting,” said presenter Aditya Bardia, MD, MPH, professor of medicine and director of translational research integration at the University of California, Los Angeles Jonsson Comprehensive Cancer Center. “Currently, up to a third of these patients eventually experience recurrence on or after adjuvant endocrine therapy for early breast cancer, and many struggle with tolerating treatment. A more effective, more tolerable treatment option is needed.”
In the global, randomized, open-label, multicenter trial, Bardia and colleagues enrolled patients with HR- positive, HER2-negative breast cancer in stages 1-3 to evaluate the safety and efficacy of giredestrant compared with the current standard-of-care therapies. All patients enrolled had received surgery and, if indicated, completed adjuvant or neoadjuvant chemotherapy. The median age of participants was 54, and 59% were postmenopausal.
In the randomized clinical trial, the researchers assigned 4,170 patients 1:1 to receive either 30 mg of giredestrant or one of four standard-of-care endocrine therapies selected at the discretion of the prescribing physician: tamoxifen, letrozole, anastrozole, or exemestane. Patients received their treatment daily for every 28-day cycle until five years had passed or unacceptable toxicity had occurred.
The researchers assessed patients for the primary endpoint of iDFS, and secondary endpoints included overall survival (OS) and distant recurrence-free interval (DRFI).
The trial met its primary endpoint at a prespecified interim analysis. After a median follow-up of 32.3 months, patients who received giredestrant had significantly better iDFS than their counterparts who received standard-of-care endocrine therapy and were 30% less likely to develop invasive disease progression at the time of follow-up.
The secondary endpoint of DRFI was also met. Patients who received giredestrant were 31% less likely than those in the standard-of-care arm to experience distant recurrence at the time of follow-up.
“Giredestrant demonstrated clinically meaningful superiority to currently well-established standard-of-care endocrine agents: aromatase inhibitors and tamoxifen,” Bardia said. “What is particularly striking and relevant is early separation of curves,” he added, referring to the preliminary OS data. Due to the limited follow-up window, the OS data were immature but showed a positive trend in favor of giredestrant over the standard of care, he explained.
The most common treatment-emergent adverse events (TEAEs) in both the giredestrant and standard-of- care arms were arthralgia, hot flashes, and headache (all of which were primarily low grade and nonnonserious), and the frequency of all of these TEAEs were similar between arms. Grade 3 and 4 TEAEs included hypertension and arthralgia. Few patients died of TEAEs (six and 16 patients died in the giredestrant and standard-of-care arms, respectively), with no treatment-related deaths in the giredestrant arm (one in the standard-of care arm).
Bradycardia—a known class effect of oral SERDs, according to Bardia—was higher in the giredestrant arm at 11.3% than in the standard-of-care arm at 3.2%. The majority were grade 1, asymptomatic, and nonserious, not requiring treatment interruption/discontinuation. Grade 2 adverse events (<1%) were confounded by concurrent conditions/antihypertensives, and all resolved. Treatment discontinuations due to TEAEs were numerically lower in the giredestrant arm at 5.3% than in the standard-of-care endocrine therapy arm at 8.2%.
“For more than a quarter of a century, tamoxifen and aromatase inhibitors have remained the standard endocrine therapy option for patients with early breast cancer,” said Bardia. “Results from lidERA demonstrate clinical superiority of giredestrant to tamoxifen and aromatase inhibitors, placing giredestrant as a new standard in endocrine therapy for patients with early-stage, HR-positive, HER2-negative breast cancer.”
The study’s limitations include limited follow-up and immature OS data.
The study was funded by F. Hoffmann-La Roche Ltd. Bardia has served as a consultant and/or advisory board member to Pfizer, Novartis, Genentech, Merck, Menarini, Gilead Sciences, Alyssum Therapeutics, Vyome, Sanofi, Daiichi Sankyo/AstraZeneca, Bristol Myers Squibb, and Eli Lilly. Bardia has conducted contracted research for or received research grants from Genentech, Novartis, Pfizer, Merck, Sanofi, OnKure Therapeutics, Menarini, Gilead Sciences, Daiichi Sankyo/AstraZeneca, and Eli Lilly.