FDA Accepts NDA for Giredestrant in Early-Stage ER-Positive Breast Cancer Under Priority Review

The FDA has accepted the new drug application (NDA) for giredestrant (Genentech), an investigational oral selective estrogen receptor degrader (SERD), under priority review for the adjuvant treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage 1 to 3 breast cancer. If approved, giredestrant could become the first oral SERD available in the curative setting and the first major advance in adjuvant endocrine therapy for early-stage ER-positive breast cancer in more than two decades.¹

The application is supported by positive findings from the phase 3 lidERA (NCT04961996) breast cancer trial, which demonstrated that giredestrant significantly reduced the risk of invasive disease recurrence or death compared with standard-of-care endocrine therapy. The FDA has assigned a Prescription Drug User Fee Act target action date of November 30, 2026.¹

“Giredestrant represents the first major endocrine therapy advance in early-stage ER-positive breast cancer in decades, where the chance for cure is highest,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a company news release. “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.”¹

LidERA Trial Demonstrates Significant Clinical Benefit

The priority review designation is based on results from the global phase 3 lidERA breast cancer trial, which enrolled more than 4100 patients with medium- or high-risk stage 1 to 3 ER-positive, HER2-negative breast cancer following surgery.¹ Patients were randomly assigned to receive either once-daily oral giredestrant or physician-selected standard endocrine therapy, including tamoxifen or an aromatase inhibitor.²

At a prespecified interim analysis after a median follow-up of about 32.3 months, giredestrant reduced the risk of invasive disease recurrence or death by 30% compared with standard endocrine therapy (HR, 0.70 [95% CI, 0.57-0.87]; P = .0014).^1,2 Three-year invasive disease-free survival rates were approximately 92.4% in the giredestrant arm compared with 89.6% in the standard-of-care group.¹ The benefit was observed across clinically relevant patient subgroups, and investigators also reported a favorable trend toward improved overall survival, although the data remain immature.^1,2

Investigators also reported that giredestrant met the secondary endpoint of distant recurrence-free interval, reducing the risk of distant recurrence by 31% relative to standard endocrine therapy.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,” Aditya Bardia, MD, MPH, professor of medicine and director of translational research integration at the University of California, Los Angeles Jonsson Comprehensive Cancer Center, said during a presentation of the study findings. “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.”²

Safety Profile Supports Long-Term Adjuvant Use

Giredestrant demonstrated a manageable safety profile that was generally consistent with previous studies.¹ Common adverse events (AEs) included arthralgia, hot flashes, and headache, with most events being low grade.² Treatment discontinuation due to AEs occurred less frequently with giredestrant than with standard endocrine therapy (5.3% vs 8.2%, respectively), suggesting favorable treatment tolerability during prolonged adjuvant therapy.¹

Although bradycardia, a recognized class effect of oral SERDs, occurred more frequently with giredestrant, most cases were grade 1, asymptomatic, and did not require treatment interruption or discontinuation.²

Potential Implications for Clinical Practice

ER-positive breast cancer accounts for approximately 70% of all breast cancer diagnoses, with the majority identified at an early stage. Despite current endocrine therapies, up to one-third of patients ultimately experience disease recurrence following adjuvant treatment, underscoring the need for more effective and better-tolerated therapeutic options.^1,3

For pharmacists, approval of giredestrant could expand endocrine therapy options in early-stage breast cancer while introducing the first oral SERD into the adjuvant setting. Pharmacists would play an important role in patient counseling, monitoring adherence during long-term therapy, identifying class-specific adverse effects such as bradycardia, and collaborating with oncology teams to optimize supportive care and treatment persistence.

REFERENCES

1. Media Release. 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. Roche. News release. June 1, 2026. Accessed June 26, 2026. https://www.roche.com/media/releases/med-cor-2026-06-02

2. Novel Endocrine Therapy Giredestrant Improves Disease-free Survival Over Standard of Care for Patients With Early-stage Breast Cancer in Phase III lidERA Trial. AACR. News release. December 10, 2025. Accessed June 26, 2026. https://www.aacr.org/about-the-aacr/newsroom/news-releases/novel-endocrine-therapy-giredestrant-improves-disease-free-survival-over-standard-of-care-for-patients-with-early-stage-breast-cancer-in-phase-iii-lidera-trial/

3. Hormone Therapy for Breast Cancer. National Cancer Institute. Updated December 2, 2025. Accessed June 26, 2026. https://www.cancer.gov/types/breast/treatment/hormone-therapy