Giredestrant PersevERA Breast Cancer Trial Misses Primary Goal

The phase 3 persevERA Breast Cancer study evaluating investigational giredestrant in combination with Ibrance (palbociclib) for people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer did not meet its primary objective, Genentech announced in a news release.

The trial, which compared the combination against Femara (letrozole) plus Ibrance in the intent-to-treat population, did not show a statistically significant improvement in progression-free survival. Despite not reaching the primary goal, a numerical improvement was observed in the group receiving giredestrant, and Genentech plans to present the full results at an upcoming medical meeting.

Main data that support the findings

The study examined giredestrant, an oral, next-generation selective estrogen receptor degrader (SERD) designed to block estrogen from binding to the receptor and trigger its breakdown. While the primary endpoint of investigator-assessed progression-free survival was not met in this specific trial, the company reported that the clinical activity of giredestrant has been validated in other settings. Specifically, the evERA study provided the first positive phase 3 readout for the drug, and the lidERA study also showed positive results in the early-stage breast cancer setting.

The scientific rationale for these efforts was further supported by the phase 2 coopERA trial, which demonstrated that giredestrant was superior to an aromatase inhibitor in reducing Ki67 levels, a marker of malignant cell division. Based on the evERA data, the U.S. Food and Drug Administration (FDA) recently accepted the new drug application for giredestrant. Genentech also intends to submit the Phase 3 lidERA data to the FDA in the coming weeks.

Dr. Levi Garraway, the company’s chief medical officer and head of global product development, stated that while persevERA did not meet its primary objective, the company remains confident in the potential for giredestrant to become a new standard-of-care endocrine therapy. He noted that the company believes there is a path forward for combining the drug with a CDK4/6 inhibitor in the adjuvant setting and is conducting further studies.

Trial details

The persevERA Breast Cancer study is a phase 3, randomized, double-blind, placebo-controlled, multicenter study. It enrolled 992 patients globally to evaluate the efficacy and safety of giredestrant plus Ibrance versus Femara plus Ibrance as a first-line treatment. The study focused on patients with ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer.

The primary endpoint of the trial was investigator-assessed progression-free survival. Key secondary endpoints included overall survival, objective response rate, duration of response and safety.

Giredestrant is currently being investigated in five company-sponsored phase 3 clinical trials:

• lidERA: Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, HER2-negative early-stage breast cancer.
• evERA: Giredestrant plus Afinitor (everolimus) versus SoC ET plus Afinitor in ER-positive, HER2-negative, locally advanced or metastatic breast cancer.
• persevERA: Giredestrant plus Ibrance versus Femara plus Ibrance in first-line metastatic breast cancer.
• pionERA: Giredestrant plus physician’s choice of CDK4/6 inhibitor versus Faslodex (fulvestrant) plus a CDK4/6 inhibitor in endocrine-resistant advanced breast cancer. This study is expected to provide a readout in 2027.
• heredERA: Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer.

Safety

The adverse events reported in the persevERA study for the giredestrant combination were manageable. According to the announcement, the safety findings were consistent with the known safety profiles of each individual treatment used in the study.

Maintaining treatment is a significant factor for patients with ER-positive breast cancer, which accounts for about 70% of all breast cancer cases. In the early-stage setting, up to one-third of people eventually experience disease recurrence on or after adjuvant endocrine therapy. Many patients must interrupt or stop treatment early due to safety or tolerability issues, which increases the risk of death. In advanced settings, resistance to endocrine therapy can increase the risk of disease progression. Genentech stated that giredestrant is designed to address the urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

Reference

“Genentech Provides Update on Phase III persevERA Study in ER-positive Advanced Breast Cancer,” news release; https://www.businesswire.com/news/home/20260308597396/en/Genentech-Provides-Update-on-Phase-III-persevERA-Study-in-ER-positive-Advanced-Breast-Cancer

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