Genentech’s Giredestrant Shows Promise in Advanced Breast Cancer Trials

Genentech has announced significant findings from its Phase III evERA study regarding the investigational drug giredestrant. The study results indicate that giredestrant, when combined with everolimus, markedly improves progression-free survival (PFS) in patients with estrogen receptor (ER)-positive advanced breast cancer. Specifically, the combination reduced the risk of disease progression or death by 44% in the intention-to-treat (ITT) population and by 62% in patients with ESR1 mutations compared to standard endocrine therapy plus everolimus.

The evERA study is pivotal as it evaluates giredestrant in individuals with locally advanced or metastatic ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have previously undergone treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy. This marks the first positive head-to-head Phase III trial to investigate a selective estrogen receptor degrader-containing regimen against a standard-of-care combination.

Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer, highlighted the urgent need for effective treatments for patients resistant to current therapies. He stated, “These study results support the potential for the giredestrant combination to become a new standard-of-care for all patients in this setting.” Dr. Erica L. Mayer, a medical oncologist at the Dana-Farber Cancer Institute, echoed this sentiment, noting the impressive benefits of the all-oral combination for patients in need of new treatment options.

The data showed a median PFS of 8.77 months for the giredestrant combination in the ITT population, compared to 5.49 months for the comparator arm. Similarly, in the ESR1-mutated group, the median PFS was 9.99 months, versus 5.45 months for standard treatment. Both populations demonstrated consistent PFS benefits across various pre-specified subgroups.

While overall survival (OS) data were not fully matured at the time of the analysis, positive trends were observed, with a hazard ratio of 0.69 in the ITT group and 0.62 in the ESR1-mutated population. Further follow-up for OS will continue in future analyses.

The trial also reported improvements in key secondary endpoints, including objective response rate and duration of response, with adverse events for the giredestrant-based combination remaining manageable and in line with known safety profiles. Notably, no new safety signals were identified.

Approximately 70% of breast cancer cases are categorized as ER-positive, a type that often develops resistance to endocrine therapies, especially after CDK inhibitor treatment. The giredestrant and everolimus combination presents a potential solution by targeting different signaling pathways while minimizing treatment impacts on patients’ daily lives.

The evERA Breast Cancer study, identified by the clinical trial number NCT05306340, is a randomized, open-label, multicenter trial assessing giredestrant’s efficacy and safety in combination with everolimus. The trial has been particularly enriched for patients with ESR1 mutations, which are prevalent in up to 40% of those with ER-positive disease in the post-CDK inhibitor setting.

As the global burden of breast cancer continues to escalate, with 2.3 million women diagnosed and 670,000 deaths annually, innovative treatments are critically needed. Genentech remains committed to advancing research to deliver effective therapies for patients with ER-positive breast cancer.

Giredestrant, a next-generation selective estrogen receptor degrader, is designed to inhibit estrogen’s effect on tumor growth by promoting the degradation of estrogen receptors. The comprehensive clinical development program for giredestrant includes five ongoing Phase III trials aimed at expanding treatment options for various breast cancer subtypes.

Founded nearly 50 years ago, Genentech is dedicated to developing and commercializing therapies for serious medical conditions, continuously striving to improve outcomes for patients facing tough diagnoses.