Giredestrant Significantly Improves Progression-Free Survival in ER-Positive Advanced Breast Cancer: Positive Phase III Results

09/22/2025 – 01:05 AM

– evERA met its co-primary endpoints; giredestrant plus everolimus demonstrated significant benefit in ITT and ESR1-mutated populations in the post-CDK inhibitor setting, compared with standard of care plus everolimus –

– The all-oral combination was well tolerated and adverse events were consistent with the known safety profiles of the individual study treatments; no new safety signals were observed –

– evERA is the first positive head-to-head Phase III trial investigating an all-oral selective estrogen receptor degrader-containing regimen versus a standard of care combination –

– Data will be presented at an upcoming medical meeting and shared with health authorities –

SOUTH SAN FRANCISCO, Calif. — Genentech, a Roche Group member, has announced positive results from its Phase III evERA study. The trial investigated giredestrant in combination with everolimus in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. These patients had previously been treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy.

The evERA study met its co-primary endpoints, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the intention-to-treat (ITT) and ESR1-mutated populations, when compared to standard-of-care endocrine therapy plus everolimus. While overall survival (OS) data remains immature, an encouraging positive trend has been observed, warranting further follow-up. The giredestrant combination exhibited a favorable safety profile, with adverse events aligning with the established safety profiles of the individual study treatments, and no new safety signals detected.

This marks a crucial milestone, as evERA is the first positive head-to-head Phase III trial evaluating an all-oral selective estrogen receptor degrader (SERD)-containing regimen against a standard-of-care combination. The implications of these findings could reshape treatment paradigms for ER-positive breast cancer.

“These results show that the giredestrant combination provides a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor,” said Genentech’s Chief Medical Officer and Head of Global Product Development. “We look forward to discussing these results with regulatory authorities with the goal of making this giredestrant-based regimen available to many people with advanced ER-positive breast cancer.”

ER-positive breast cancer represents approximately 70% of all breast cancer cases. Despite continuous advancements in treatment, this subtype remains a significant therapeutic challenge, largely due to its inherent biological complexity.
Resistance to endocrine therapies, particularly after CDK 4/6 inhibitor treatment, significantly elevates the risk of disease progression and poor patient outcomes.

Combination therapies, such as giredestrant plus everolimus, offer a promising strategy by simultaneously targeting distinct signaling pathways. This dual approach holds the potential to enhance therapeutic efficacy and improve patient outcomes. Furthermore, the all-oral administration of this regimen could significantly improve patient convenience and quality of life, eliminating the need for injections. From a commercial perspective, the user-friendly all oral option could make this combination product more desirable compared to other treatments.

Genentech’s comprehensive giredestrant clinical development program encompasses multiple treatment settings and lines of therapy, reflecting the company’s dedication to delivering innovative medicines to a broad spectrum of patients with ER-positive breast cancer.

The data from the evERA study will now be submitted to health authorities, with the objective of expediting the availability of this potential treatment option to patients in need. The company anticipates a potentially accelerated approval pathway given the unmet clinical need and significant benefit demonstrated in the trial.

About the evERA Breast Cancer study

The evERA trial (NCT05306340) is a Phase III, randomized, open-label, multicenter study designed to evaluate the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. All participants had prior treatment with a CDK 4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints of the study are investigator-assessed progression-free survival in the intention-to-treat (ITT) and ESR1-mutated populations, measured from randomization to disease progression or death from any cause. The trial design incorporated enrichment for ESR1-mutated patients to assess efficacy in this specific subgroup, which accounts for up to 40% of ER-positive disease cases post-CDK inhibitor treatment. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate, and safety.

About estrogen receptor (ER)-positive breast cancer

Globally, breast cancer’s impact continues to grow, with 2.3 million diagnoses and 670,000 deaths anually. Breast cancer is the leading cause of cancer-related deaths among women and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining characteristic is the presence of estrogen receptors on tumor cells, which can contribute to tumor growth when bound by estrogen.

Despite treatment advances, the biological complexity of ER-positive breast cancer makes it a challenging disease to treat. Patients often face the risk of disease progression, treatment side effects, and resistance to endocrine therapies. Thus, there is a significant need for more effective treatments that can delay clinical progression and reduce the treatment burden in patient’s lives.

About giredestrant

Giredestrant is an investigational oral, next-generation selective estrogen receptor degrader (SERD) and full antagonist. It represents a potential advancement in endocrine therapy for ER-positive breast cancer.

The mechanism of action of giredestrant involves blocking estrogen from binding to the estrogen receptor (ER), leading to the receptor’s breakdown (degradation) and thereby halting or slowing down the growth of cancer cells.

Currently, the giredestrant clinical development program involves five company-sponsored Phase III clinical trials across multiple treatment settings and lines of therapy, aimed at benefiting as many patients as possible:

• Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
• Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
• Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
• Giredestrant plus investigator’s choice of a cyclin-dependent kinase (CDK) 4/6 inhibitor versus fulvestrant plus a CDK 4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
• Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

About Genentech in Breast Cancer

Genentech has dedicated over 30 years to advancing breast cancer research, striving to improve outcomes for as many people with this disease as possible. Their established medicines, along with companion diagnostic tests, have facilitated breakthroughs in HER2-positive and triple-negative breast cancers. Continiously seeking to understand breast cancer deeply, Genentech aims to use new biomarkers and approaches to treatment for other subtypes of the disease, including estrogen receptor-positive breast cancer.

About Genentech

Founded nearly 50 years ago, Genentech is a biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.