Adjuvant Giredestrant Preserves QOL With Sustained Tolerability in ER+, HER2– Early Breast Cancer

Adjuvant giredestrant sustained physical functioning, role functioning, and health-related quality of life (HRQOL) and was associated with sustained low adverse effect (AE) bother vs standard-of-care (SOC) endocrine therapy in patients with estrogen receptor (ER)–positive, HER2-negative early breast cancer, according to Patient-reported outcome (PRO) data from the phase 3 lidERA Breast Cancer trial (NCT04961996) presented at the 2026 ESMO Congress.¹

Fewer patients receiving giredestrant also reported frequent or almost constant joint pain than those receiving SOC endocrine therapy, whereas hot flash and fatigue profiles were comparable between the arms. The findings add patient-reported context to the previously reported improvement in invasive disease–free survival (IDFS) seen with giredestrant in lidERA Breast Cancer.²

In the current analysis, PRO questionnaire completion rates exceeded 75% at baseline and remained above 75% through most treatment cycles.¹ At a median follow-up of 32.3 months, more than 50% of evaluable patients receiving giredestrant reported not being bothered at all by AEs on the Functional Assessment of Cancer Therapy–General (FACT-G) item GP5, a consistently higher proportion of patients than those who received SOC endocrine therapy at every time point assessed. At cycle 3, 53% of evaluable patients receiving giredestrant (812/1543) vs 45% of those receiving SOC (692/1533) reported no AE bother; these respective proportions of patients were 51% (n = 799/1572) vs 47% (n = 714/1508) at cycle 12, 54% (n = 820/1519) vs 50% (n = 701/1416) at cycle 24, and 51% (n = 130/256) vs 46% (n = 100/219) at cycle 42. Across these time points, 80% to 83% of patients receiving giredestrant reported being bothered a little bit or less by AEs vs 76% to 80% of those receiving SOC.

“This demonstrates a sustained tolerability with low overall bother from AEs, and this is relevant in clinical practice,” Gustavo Werutsky, MD, PhD, of the Centro de Pesquisa em Oncologia Hospital São Lucas PUCRS in Porto Alegre, Brazil, stated in a presentation of the data.

How was the lidERA Breast Cancer trial designed?

The global, randomized, open-label, multicenter phase 3 trial enrolled 4170 patients with ER-positive, HER2-negative stage I to III early breast cancer at medium or high risk of recurrence between August 2021 and September 2023.² Patients were randomly assigned 1:1 to receive giredestrant at 30 mg orally once daily (n = 2084) or SOC endocrine therapy (n = 2086) for at least 5 years. Premenopausal patients who received an aromatase inhibitor or giredestrant also underwent ovarian function suppression with a luteinizing hormone–releasing hormone agonist.

PROs were assessed with 3 instruments.¹ The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C-30 (EORTC QLQ-C30) evaluated physical function, role function, and HRQOL, with a deterioration of at least 10 points considered clinically meaningful. The PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) evaluated joint pain (frequency, severity, interference), hot flashes (frequency, severity), and fatigue (severity, interference). FACT-G item GP5 assessed overall bother from AEs. At the August 8, 2025, data cutoff, fewer than 50% of patients in the overall population had completed 36 cycles of treatment, and all PRO analyses were descriptive.

What did the primary analysis of lidERA Breast Cancer show?

Primary results from lidERA Breast Cancer were presented at the 2025 San Antonio Breast Cancer Symposium.² At a median follow-up of 32.3 months, giredestrant reduced the risk of invasive disease recurrence or death by 30% vs SOC (HR, 0.70; 95% CI, 0.57-0.87; P = .0014), with 3-year IDFS rates of 92.4% vs 89.6%, respectively. Distant recurrence–free interval was also improved with giredestrant (HR, 0.69; 95% CI, 0.54-0.89), and an interim overall survival analysis favored the giredestrant arm but was immature (HR, 0.79; 95% CI, 0.56-1.12; P = .1863).

AEs led to treatment discontinuation in 5.3% of safety-evaluable patients receiving giredestrant (n = 2060) vs 8.2% of those receiving SOC (n = 2074). Discontinuations due to arthralgia occurred in 1.6% vs 3.7% of patients, respectively, and discontinuations due to hot flashes occurred in less than 0.1% vs 0.8% of patients, respectively.

How did giredestrant affect functioning, joint pain, and other symptoms in lidERA Breast Cancer?

Baseline physical functioning (giredestrant, 86.8; SOC ET, 86.6), role functioning (83.9; 84.0), and HRQOL (74.6; 73.7) scores on the EORTC QLQ-C30 were high and comparable between the arms. These scores were maintained through more than 3 years of treatment, with no clinically meaningful deterioration observed in either arm.

More patients receiving giredestrant reported never experiencing joint pain compared with those receiving SOC, and although joint pain frequency increased in both arms with longer treatment, fewer patients in the giredestrant arm reported frequent or almost constant joint pain. Severity and interference of joint pain were comparable between the arms.

In an analysis limited to patients receiving aromatase inhibitors, the proportion of patients reporting never having joint pain was higher with giredestrant vs SOC at each assessment through cycle 15, with the largest differences during the first 6 months of treatment, when early discontinuation of endocrine therapy peaked: 34.9% vs 28.2%, respectively, at cycle 2 (+ 6.7%); 29.7% vs 22.2% at cycle 3 (+ 7.5%); and 23.4% vs 17.4% at cycle 6 (+ 6.0%). At cycle 6, the odds of reporting never having joint pain were 44% higher with giredestrant (OR, 1.44; 95% CI, 1.20-1.73; descriptive P = .0001). Clinician-reported arthralgia rates were similar between the giredestrant arm and the aromatase inhibitor subgroup.

Most patients in both arms reported hot flashes of low frequency and moderate or lower severity, and most patients reported mild fatigue severity with minimal interference with daily life; these results were comparable between the arms.

What are the next steps for developing giredestrant in early breast cancer?

The FDA granted priority review to a new drug application seeking the approval of adjuvant giredestrant for patients with ER-positive, HER2-negative stage I to III breast cancer based on the lidERA Breast Cancer data, with a Prescription Drug User Fee Act target action date of November 30, 2026.³

Disclosures: Werutsky reported performing advisory board/consultant roles for AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Merck & Co., Novartis, Olema, and Roche; receiving research grants to his institution from Astellas Pharma, AstraZeneca, Bayer, BeOne, Genmab, GlaxoSmithKline, Janssen, Libbs, Merck & Co., Novartis, Pfizer, Roche, Takeda Pharmaceutical; and receiving research support in the form of third-party medical writing assistance for the presentation from Daniel Clyde, PhD, of Nucleus Global, an Inizio Company, provided by F. Hoffmann-La Roche Ltd.

Supported in part by AstraZeneca and Daiichi Sankyo, content independently developed by OncLive.

References

1. Werutsky G, Bardia A, Geyer CE, et al. Patient (pt)-reported outcomes (PROs) from the phase III lidERA Breast Cancer (BC) trial of giredestrant (GIRE) in pts with oestrogen receptor-positive, HER2-negative early BC (ER+, HER2– eBC). Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 538RO.
2. Bardia AL, Schmid P, Martín M, 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: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract GS1-10.
3. FDA accepts new drug application for Roche’s giredestrant in ER-positive early-stage breast cancer, the first and only oral SERD with positive phase III results in the curative setting. News release. Roche. June 2, 2026. Accessed October 23, 2026. https://www.roche.com/media/releases/med-cor-2026-06-02