Roche announced results from the phase III persevERA Breast Cancer study evaluating investigational giredestrant in combination with palbociclib for people with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. The study did not meet its primary objective of a statistically significant improvement in progression-free survival in the intent-to-treat population versus letrozole plus palbociclib, but a numerical improvement was observed. The adverse events for the giredestrant combination were manageable and consistent with the known safety profiles of each individual treatment.
The giredestrant clinical development programme is made up of distinct studies designed to reflect the specific disease biology of each stage of breast cancer. Roche will continue to advance the clinical development programme to identify the people with ER-positive breast cancer who can derive the greatest benefit from giredestrant. evERA was the first positive phase III readout for giredestrant, followed by lidERA in the early-stage setting.
The scientific rationale for lidERA was supported by prior results in the neoadjuvant setting, including the phase II coopERA trial showing that giredestrant was superior to an aromatase inhibitor in reducing malignant cell division (Ki67 levels). This growing body of evidence underscores the potential of giredestrant to become a new standard-of-care endocrine therapy across ER-positive early-stage and advanced breast cancer. persevERA is the first of two distinct phase III studies in the first-line setting; the pionERA study of giredestrant in combination with physician?s choice of cyclin-dependent kinase (CDK)4/6 inhibitor in endocrine-resistant ER-positive, HER2-negative breast cancer is expected to readout in 2027.
The United States Food and Drug Administration (FDA) recently accepted the New Drug Application based on the evERA data. In the coming weeks, Roche will submit the giredestrant phase III lidERA data in early-stage breast cancer to the FDA. The full results from persevERA will be presented at an upcoming medical meeting.
persevERA Breast Cancer [NCT04546009] is a phase III, randomised, double-blind, placebo-controlled, multicentre study evaluating the efficacy and safety of giredestrant plus palbociclib versus letrozole plus palbociclib as first-line treatment for people with oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, locally advanced or metastatic breast cancer. The study enrolled 992 patients globally. The primary endpoint is investigator-assessed progression-free survival.
Key secondary endpoints include overall survival, objective response rate, duration of response and safety. Giredestrant is an investigational, oral, potent next-generation selective oestrogen receptor degrader and full antagonist. Giredestrant is designed to block oestrogen from binding to the oestrogen receptor, triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.
Giredestrant has an extensive clinical development programme and is being investigated in five company-sponsored phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible: Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996); Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340); Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009); Giredestrant plus investigator?s choice of a cyclin-dependent kinase (CDK)4/6 inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748); Giredestrant plus Phesgo (pertuzumab, trastuzumab, and hyaluronidase subcutaneous) versus Phesgo in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798).
