Giredestrant Becomes First Oral SERD to Show iDFS Benefit As Adjuvant Therapy in Early ER+, HER2-Negative Breast Cancer

The oral selective estrogen receptor degrader (SERD) giredestrant demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival (iDFS) compared with standard-of-care (SOC) endocrine monotherapy for patients with estrogen receptor (ER)–positive, HER2-negative early-stage breast cancer, meeting the primary end point of the phase 3 lidERA Breast Cancer study (NCT04961996). 1

According to findings from a pre-planned interim analysis, overall survival (OS) data were immature at the time of interim analysis, but demonstrated a positive trend with giredestrant. The agent was also well tolerated, with no unexpected safety findings observed. These results mark giredestrant as the first oral SERD to show superior efficacy in the adjuvant setting, according to the news release.

Data from lidERA will be presented at an upcoming medical meeting and shared with health authorities in coming months.

“Today’s results underscore the potential of giredestrant as a new endocrine therapy of choice for people with early-stage breast cancer, where there is a chance for cure,” Levi Garraway, MD, PhD, Roche’s chief medical officer and head of Global Product Development shared in a news release. “Given that ER-positive breast cancer accounts for approximately 70% of cases diagnosed, these findings—together with recent data in the advanced ER-positive setting—suggest that giredestrant has the potential to improve outcomes for many people with this disease.”

lidERA Breast Cancer is the second positive phase 3 readout for giredestrant, following findings from the phase 3 evERA trial (NCT05306340), which were presented at the 2025 ESMO Congress. In this trial, a significant progression-free survival benefit was seen with giredestrant plus everolimus (Afinitor) vs SOC endocrine therapy plus everolimus in advanced ER-positive, HER2-negative disease.

What was the design of the lidERA Breast Cancer study?

The phase 3 lidERA Breast Cancer study is a randomized, open-label, multicenter trial designed to evaluate the efficacy and safety of adjuvant giredestrant compared with SOC endocrine therapy in patients with medium- or high-risk stage I to III ER-positive, HER2-negative early breast cancer.2 The study enrolled more than 4,100 participants across global sites, reflecting the broad population in whom adjuvant endocrine therapy is routinely indicated.

The primary end point of the study was iDFS excluding second primary non–breast cancers. Key secondary end points include OS, iDFS inclusive of second primary non–breast cancers, disease-free survival, and safety.

What other investigations of giredestrant in breast cancer are ongoing?

In addition to the lidERA Breast Cancer and evERA studies, Giredestrant is being evaluated in 3 other company-sponsored phase 3 trials spanning early-stage, locally advanced, and metastatic breast cancer settings.1 These include:

• persevERA Breast Cancer (NCT04546009): Giredestrant plus palbociclib vs letrozole plus palbociclib (Ibrance) in endocrine-sensitive, recurrent locally advanced or metastatic ER-positive, HER2-negative breast cancer.
• pionERA Breast Cancer (NCT06065748): Giredestrant plus investigator’s choice of CDK4/6 inhibitor vs fulvestrant (Faslodex) plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy.
• heredERA Breast Cancer (NCT05296798): Giredestrant plus pertuzumab (Perjeta), trastuzumab (Herceptin), and hyaluronidase (Phesgo) vs the combination in ER-positive, HER2-positive locally advanced or metastatic breast cancer.

References

1. [Ad hoc announcement pursuant to Art. 53 LR] Roche’s giredestrant becomes the first oral SERD to show superior invasive disease-free survival in early breast cancer. Roche. News Release. November 17, 2025. Accessed November 18, 2025. https://www.roche.com/media/releases/med-cor-2025-11-18
2. A study evaluating the efficacy and safety of adjuvant giredestrant compared with physician’s choice of adjuvant endocrine monotherapy in participants with estrogen receptor–positive, HER2-negative early breast cancer (lidERA Breast Cancer). Clinicaltrials.gov Updated August 24, 2025. Accessed November 18, 2025.