FDA Grants Priority Review to Giredestrant in ER+/HER2– Early Breast Cancer

The FDA has both accepted and granted priority review to a new drug application (NDA) for giredestrant as an adjuvant treatment for patients with estrogen receptor (ER)–positive, HER2-negative stage I to III breast cancer, according to a press release from the developer, Genentech.¹ The FDA has established a Prescription Drug User Fee Act date of November 30, 2026.

Giredestrant is an oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist designed to block estrogen from binding to the estrogen receptor.

The NDA contained data from the phase 3 lidERA Breast Cancer study (NCT04961996), which were previously sharedat the 2025 San Antonio Breast Cancer Symposium (SABCS), showing that giredestrant reduced the risk of invasive disease recurrence or death (iDFS) by 30% vs standard endocrine therapy (HR, 0.70; 95% CI, 0.57-0.87; P = .0014).² The 3-year iDFS rate was 92.4% with giredestrant vs 89.6% with standard of care. Notably, the iDFS benefit was consistent across all key prespecified subgroups, with particular benefit in patients aged 46 to 55 years (HR, 0.54, 95% CI, 0.36-0.80) and with AJCC stage II disease at surgery (HR, 0.58; 95% CI, 0.39-0.85).

Recently, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, findings from lidERA were shared on patients stratified by menopausal status.³ Regardless of menopausal status, the giredestrant benefit for iDFS was sustained across patients. Among pre-menopausal patients, the 3-year iDFS rate was 94.0% with giredestrant vs 91.5% with standard of care (HR, 0.65; 95% CI, 0.44-0.95). Exploratory analyses showed that, when divided by standard-of-care endocrine therapy received, the HR for giredestrant vs aromatase inhibitors was 0.66 (95% CI, 0.43-1.01) and 0.62 (95% CI, 0.38-1.03) vs tamoxifen.

Among post-menopausal patients, the 3-year iDFS rate was 91.3% with giredestrant vs 88.3% with standard endocrine therapy (HR, 0.74; 95% CI, 0.57-0.96). Exploratory analyses revealed HRs of 0.77 (95% CI, 0.59-1.00) and 0.37 (95% CI, 0.19-0.73) in favor of giredestrant with aromatase inhibitor and tamoxifen, respectively.

At the time of these analyses, overall survival (OS) data were immature, although a “clear” positive trend was observed, per the press release. Investigators plan to continue OS follow-up to the next analysis.

“Giredestrant represents the first major endocrine therapy advance in early-stage ER-positive breast cancer in decades, where the chance for cure is highest,” stated Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech.¹ “The FDA’s filing acceptance brings us closer to delivering a new standard-of-care with the potential to fundamentally change the treatment paradigm for people with early-stage disease.”

lidERA was a randomized, open-label trial that enrolled 4170 patients with stage I to III, ER-positive, HER2-negative early breast cancer who had completed breast cancer surgery within 12 months and any indicated neoadjuvant/adjuvant chemotherapy.

Patients were randomly assigned 1:1 to receive either giredestrant orally at 30 mg daily or endocrine therapy with either tamoxifen, anastrozole, letrozole, and exemestane; treatment continued for at least 5 years, and after treatment concluded, follow-up was at least 5 years.

The primary end point of the trial was iDFS. Secondary end points included disease-free survival, OS, and safety.

Regarding safety, giredestrant was well tolerated, with manageable adverse effects consistent with previously known data. In the giredestrant arm, 5.3% of patients discontinued treatment compared with 8.2% of the standard-of-care endocrine therapy arm.

References

1. FDA accepts new drug application for Genentech’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. Genentech. June 1, 2026. Accessed June 3, 2026. https://tinyurl.com/4wh537hv
2. Bardia A, 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. Schmid P, Geyer CE Jr, Martín M, et al. Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor-positive, HER2-negative early breast cancer (ER+, HER2- eBC) in the phase III lidERA BC clinical trial: results by menopausal status. J Clin Oncol. 2026;44(suppl 16):502. doi:10.1200/JCO.2026.44.16_suppl.502