Roche’s investigational breast cancer drug giredestrant significantly extended progression-free survival when combined with everolimus, according to detailed results from the phase III evERA Breast Cancer study published in The New England Journal of Medicine.
The trial evaluated giredestrant, an investigational oral selective oestrogen receptor degrader (SERD), in combination with everolimus in people with oestrogen receptor (ER)-positive, locally advanced or metastatic breast cancer whose disease had progressed or recurred after treatment with a CDK4/6 inhibitor and endocrine therapy.
The benefit was particularly pronounced in patients whose tumours carried ESR1 mutations. Median progression-free survival (PFS) reached 10.0 months with giredestrant plus everolimus, compared with 5.5 months with standard endocrine therapy plus everolimus. The risk of disease progression or death was reduced by 62%.
In the overall intent-to-treat population, median PFS was 8.8 months versus 5.5 months, representing a 44% reduction in the risk of progression or death.
“Despite advancements with CDK4/6 inhibitor treatment in the first-line setting, many people with advanced breast cancer will eventually experience disease progression as their tumours become resistant to endocrine therapy,” said Erica L. Mayer, Medical Oncologist at Dana-Farber Cancer Institute.
"The evERA trial demonstrated that the giredestrant combination significantly delayed disease progression, potentially offering a promising all-oral treatment option in a setting where there remains a need for additional treatments to improve patient outcomes.”
Overall survival data remain immature, although the study showed a positive trend in both the overall population and the ESR1-mutated subgroup. Follow-up will continue through the next overall survival analysis.
The safety profile of the giredestrant combination was manageable and consistent with the established safety profiles of the individual medicines. Roche said there were no unexpected safety findings, including no photopsia and low rates of bradycardia.
“The evERA results represent an important step forward for people with ER-positive advanced breast cancer and underscore the potential for giredestrant to help address the challenge of disease progression in this setting,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development.
"Together with the positive phase III lidERA results in early breast cancer, these findings reinforce the potential of giredestrant to redefine care in both metastatic and early disease settings.”
HR-positive, HER2-negative breast cancer accounts for approximately 70% of breast cancer cases. Resistance to endocrine therapy, particularly after CDK4/6 inhibitor treatment, remains a major challenge and is associated with disease progression and poor outcomes.
The evERA study was the first positive phase III readout for giredestrant, followed by positive results from the phase III lidERA Breast Cancer study in early-stage disease.
Roche is continuing to develop giredestrant across different stages and lines of therapy in HR-positive breast cancer, with the aim of expanding treatment options for patients facing endocrine-resistant disease.
