The FDA will review data for adjuvant giredestrant in ER-positive, HER2-negative early-stage breast cancer after positive iDFS data from LidERA.
The FDA has accepted and granted priority review to a new drug application (NDA) seeking the approval of giredestrant as adjuvant treatment for adult patients with estrogen receptor (ER)–positive, HER2-negative, stage I to III breast cancer; the Prescription Drug User Fee Act target action date is November 30, 2026.1
The NDA is supported by data from the phase 3 lidERA Breast Cancer trial (NCT04961996), which demonstrated that adjuvant giredestrant reduced the risk of invasive disease recurrence or death vs standard-of-care (SOC) endocrine therapy by 30% in patients with medium- or high-risk stage I to III ER-positive, HER2-negative early-stage breast cancer (HR, 0.70; 95% CI, 0.57-0.87; P = .0014). At the 3-year landmark analysis, 92.4% of patients in the giredestrant arm were alive and free of invasive disease compared with 89.6% in the SOC endocrine therapy arm.
“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, stated in a news release. “The FDA’s filing acceptance brings us closer to delivering a new SOC with the potential to fundamentally change the treatment paradigm for people with early-stage disease.”
LidERA Breast Cancer was a randomized, open-label, multicenter phase 3 study that evaluated adjuvant giredestrant vs physician’s choice of SOC endocrine monotherapy in patients with ER-positive, HER2-negative early-stage breast cancer at medium or high risk of recurrence.2 Other key inclusion criteria included undergoing definitive surgery of primary breast tumor(s) and axillary lymph nodes, an ECOG performance status of 0 to 2, and adequate organ function.
In the investigational arm, patients received oral giredestrant at 30 mg once daily on days 1 through 28 of each 28-day cycle for 5 years or until disease recurrence or unacceptable toxicity. Patients in the comparator arm received physician’s choice of endocrine therapy, limited to tamoxifen or one of the specified third-generation aromatase inhibitors: letrozole (Femara), anastrozole (Arimidex), or exemestane (Aromasin).
The primary end point was invasive disease–free survival (iDFS), excluding second primary non-breast cancers. Key secondary end points included overall survival (OS), iDFS including second primary non-breast cancers, DFS, and safety.
The iDFS benefit was consistent across clinically relevant subgroups. OS data were immature at the time of the reported analysis, and follow-up for OS is continuing to the next analysis. However, a clear positive trend in OS was observed in favor of giredestrant.
Giredestrant was described as well tolerated, with adverse effects characterized as manageable and consistent with the known safety profile of the agent. Treatment discontinuation occurred in 5.3% of patients in the giredestrant arm vs 8.2% of patients in the endocrine therapy arm.
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