Giredestrant Outperforms Standard of Care in ER+/HER2– Early Breast Cancer

According to interim data from the phase 3 lidERA trial (NCT04961996), giredestrant (GDC-9545) as adjuvant treatment generated significant invasive disease-free survival (IDFS) improvements in estrogen receptor (ER)–positive, HER2-negative early-stage breast cancer, outperforming standard of care.¹

Showing a statistically significant and clinically meaningful improvement in IDFS vs standard of care endocrine monotherapy, the trial met its primary end point, becoming the first agent in its class to demonstrate such a superior benefit in the adjuvant setting.

While overall survival (OS) data were immature at the time of the analysis, a positive trend favoring giredestrant was observed. In terms of safety, the agent exhibited a safety profile that was expected and consistent with what was previously established for the agent, with no new safety signals. Full data will be presented at an upcoming medical meeting and shared with regulatory authorities.

“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,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Genentech, in a news release.¹ “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.”

Giredestrant is an oral selective estrogen receptor degrader (SERD) that is emerging as a promising endocrine treatment option for patients with hormone receptor–positive breast cancer.² These encouraging data contribute to a growing body of positive clinical data supporting oral SERDs, feeding into a greater potential shift in the breast cancer treatment paradigm. As evidence continues to build, oral SERDs like giredestrant are poised to play an increasingly central role in the management of this common breast cancer subtype.

Studies of Giredestrant

The phase 3 lidERA trial is a randomized, open-label, multicenter study evaluating the efficacy and safety of adjuvant giredestrant against standard endocrine therapy in patients with ER-positive, HER2-negative early breast cancer.³ The primary end point of the trial is IDFS; secondary end points include OS, disease-free survival, quality of life, and safety.

The study has enrolled approximately 4200 patients with medium- and high-risk, stage I through III, ER-positive, HER2-negative early breast cancer across 626 global sites. Patients have been randomly assigned to receive either 30 mg of oral giredestrant administered once daily or physician’s choice of endocrine therapy. Treatment is to continue for 5 years or until disease recurrence or unacceptable toxicity.

Additionally, in an exploratory substudy evaluating a giredestrant-based combination, a subset of the patient population is receiving 30 mg of oral giredestrant once daily plus the cyclin-dependent kinase 4/6 inhibitor abemaciclib (Verzenio) at 150 mg twice daily.

In the same indication, the completed phase 2 coopERA trial (NCT04436744) evaluated giredestrant plus palbociclib (Ibrance) against the aromatase inhibitor anastrozole (Arimidex) plus palbociclib. Here, the giredestrant combination resulted in a greater relative reduction in Ki67 score compared with anastrozole, suggesting that giredestrant induces greater Ki67 suppression.

Giredestrant is also under clinical evaluation in the randomized phase 3 evERA trial (NCT05306340) in combination with everolimus (Afinitor) in 373 patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. The trial is assessing the efficacy and safety of the combination compared with standard of care endocrine therapy.

Preliminary findings from the evERA trial recently presented at the 2025 European Society for Medical Oncology Congress showed an improvement in progression-free survival (PFS) by the combination vs standard of care (median PFS, 8.77 vs 5.49 months), amounting to a 44% reduction in the risk of progression or death (HR, 0.56; 95% CI, 0.44-0.71; P < .0001).

REFERENCES

1. Genentech’s giredestrant becomes the first oral SERD to show superior invasive disease-free survival in early breast cancer. News release. Genentech. November 17, 2025. Accessed November 18, 2025. https://tinyurl.com/78kt7txy

2. Gheysen M, Punie K, Wildiers H, Neven P. Oral SERDs changing the scenery in hormone receptor positive breast cancer, a comprehensive review. Cancer Treat Rev. 2024;130:102825. doi:10.1016/j.ctrv.2024.102825

3. 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. https://clinicaltrials.gov/study/NCT04961996