Genentech Reports Promising Results for Giredestrant in Breast Cancer Trials

Genentech, a member of the Roche Group, announced significant findings from its Phase III evERA Breast Cancer study on October 18, 2025. The study revealed that the investigational drug giredestrant, when combined with everolimus, notably improved progression-free survival (PFS) for patients with estrogen receptor (ER)-positive advanced breast cancer. The results indicated a 44% reduction in the risk of disease progression or death in the overall study population and a remarkable 62% in those with ESR1 mutations compared to standard endocrine therapy plus everolimus.

Study Highlights and Implications

The evERA study evaluated giredestrant in patients diagnosed with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer who had previously been treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy. This trial represents a pivotal moment, being the first positive head-to-head Phase III trial that explores a selective estrogen receptor degrader (SERD) combination against standard-of-care therapies.

Dr. Levi Garraway, Genentech’s Chief Medical Officer, expressed optimism about the findings, stating, “A particularly high unmet need remains for people who become resistant to endocrine therapies and CDK inhibitors.” He highlighted the potential for the giredestrant combination to establish a new standard of care in this challenging treatment landscape. Dr. Erica L. Mayer, a medical oncologist at Dana-Farber Cancer Institute, noted the impressive benefits of the all-oral combination, emphasizing its ability to improve patient outcomes in need of new therapies.

The trial demonstrated a statistically significant improvement in PFS, with the median PFS reaching 8.77 months for the combination therapy versus 5.49 months for the standard of care in the intention-to-treat (ITT) population. For those with ESR1 mutations, the median PFS was 9.99 months compared to 5.45 months in the comparator group. Both populations saw consistent PFS benefits across various pre-specified subgroups.

While overall survival (OS) data remains immature, a positive trend was noted in both the ITT (hazard ratio [HR]=0.69) and ESR1-mutated populations (HR=0.62). Continuous follow-up for OS will be essential in subsequent analyses of the data.

Potential Impact on Treatment Options

The giredestrant and everolimus combination also showed significant improvements in key secondary endpoints, including objective response rate and duration of response, compared to standard therapies. Adverse events associated with the combination were manageable and consistent with existing safety profiles, with no new safety signals reported.

ER-positive breast cancer is a major subtype, accounting for approximately 70% of all breast cancer cases. The risk of disease progression remains high, particularly for patients experiencing resistance to endocrine therapies. The all-oral nature of the giredestrant and everolimus combination could provide a patient-friendly alternative, reducing the need for injections while effectively targeting different cancer signaling pathways.

Genentech is committed to advancing treatments for ER-positive breast cancer and has initiated a comprehensive clinical development program for giredestrant, with multiple ongoing Phase III trials. This dedication reflects the urgency for effective treatments that can alleviate the burden of disease progression and enhance patients’ quality of life.

The full results of the evERA study are set to be presented at the European Society for Medical Oncology Congress 2025, and findings will be shared with health authorities in hopes of expediting access to this promising treatment option.