Genentech will be heading to regulators after the Phase III success of its oral selective oestrogen receptor degrader (SERD) and full antagonist therapy in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer.
In the evERA study (NCT05306340), giredestrant, used in combination with everolimus, met both co-primary endpoints. The drug demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in both the intention-to-treat and ESR1-mutated populations, compared with standard-of-care (SoC) endocrine therapy plus everolimus.
While overall survival (OS) data is currently immature, Genentech said there is a clear positive trend in favour of giredestrant.
The combination was well tolerated, with adverse events (AEs) remaining consistent with the known safety profiles of the individual study treatments, and no new safety signals were observed.
Genentech said its study marks the first positive head-to-head Phase III trial investigating an all-oral selective oestrogen receptor degrader-containing regimen versus a SoC combination.
The trial enrolled 373 patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer previously treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor and endocrine therapy.
A part of the Roche group, Genentech CMO and global product development head Dr Levi Garraway said: “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.
"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.”
Genentech's giredestrant is an investigational oral, next-generation SERD and full antagonist. It acts by blocking oestrogen from binding to the ER, triggering its breakdown to stop or slow down the growth of cancer cells. The drug is being investigated in five other Phase III trials, all in breast cancer indications.
If approved, GlobalData predicts the drug will reach $675m in sales in 2031. GlobalData is the parent company of Clinical Trials Arena.
Global burden of breast cancer grows
Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.
ER-positive breast cancer accounts for approximately 70% of breast cancer cases. Despite treatment advances, ER-positive breast cancer remains particularly challenging to manage due to its biological complexity.
Patients often face the risk of disease progression, AEs, and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.
Eli Lilly has also seen success with its oral SERD, imlunestrant, which cut the risk of disease progression or death by 38%; however, only a subset of patients benefited.
