Genentech’s Giredestrant Shows Promise in Advanced Breast Cancer Trial
Genentech announced significant findings from its Phase III evERA study, revealing that the investigational drug giredestrant, when combined with everolimus, markedly improved progression-free survival (PFS) in patients with estrogen receptor (ER)-positive advanced breast cancer. The study demonstrated a 44% reduction in the risk of disease progression or death in the intention-to-treat (ITT) population and a 62% reduction in those with ESR1 mutations compared to standard endocrine therapy plus everolimus.
The evERA study is pivotal, examining giredestrant in individuals with locally advanced or metastatic ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who had previously undergone treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This trial represents the first positive head-to-head Phase III investigation of a regimen containing a selective estrogen receptor degrader versus a standard-of-care combination.
Key Findings and Implications
The results were presented at the European Society for Medical Oncology Congress 2025, with Genentech expressing commitment to share the findings with health authorities to expedite access for patients. “A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors,” stated Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer. He emphasized the potential of the giredestrant combination to establish a new standard of care.
Dr. Erica L. Mayer, a medical oncologist at Dana-Farber Cancer Institute, noted that resistance to standard therapies is common in this patient population. She remarked on the impressive clinically meaningful benefit observed with the all-oral giredestrant and everolimus combination, which could significantly improve patient outcomes.
The giredestrant combination achieved a median PFS of 8.77 months in the ITT population, compared to 5.49 months for the comparator arm (stratified hazard ratio [HR]=0.56; p-value <0.0001). In the ESR1-mutated group, median PFS was 9.99 months versus 5.45 months (HR=0.38; p-value <0.0001). These findings were consistent across various pre-specified subgroups. While overall survival (OS) data were not fully mature at the time of analysis, there was a positive trend in both the ITT (HR=0.69, p-value=0.0473) and ESR1-mutated populations (HR=0.62, p-value=0.0566). Follow-up analyses will continue to evaluate OS. Additionally, the giredestrant and everolimus combination exhibited improvements in secondary endpoints, including objective response rate and duration of response. Adverse events were manageable and aligned with known safety profiles, with no new safety signals reported.
Understanding ER-Positive Breast Cancer
Approximately 70% of breast cancer cases are classified as ER-positive. Patients with this type of cancer often encounter challenges with disease progression and treatment resistance, particularly after CDK inhibitor therapy. There is an urgent demand for new treatment options that can effectively combat these issues while minimizing treatment burdens.
Giredestrant, an investigational oral selective estrogen receptor degrader, aims to block estrogen from binding to the estrogen receptor, thereby promoting tumor cell degradation. Genentech’s extensive clinical development program for giredestrant includes five Phase III trials across various treatment settings, demonstrating their commitment to expanding treatment options for patients with ER-positive breast cancer.
As the landscape of breast cancer treatment continues to evolve, the findings from the evERA study underscore the importance of innovative therapies that address the specific needs of patients facing advanced disease. Genentech’s ongoing research efforts reflect a broader goal of enhancing patient outcomes and quality of life in this challenging therapeutic area.
