Giredestrant Plus Afinitor Improves Outcomes in ER-Positive Breast Cancer

Phase 3 study results show that giredestrant significantly improved survival without tumor progression in ER-positive advanced breast cancer, according to a news release from Roche.

This marks the first positive phase 3 head-to-head trial of an all-oral selective estrogen receptor degrader regimen compared with standard care.

The trial met its co-primary goals, showing that giredestrant plus Afinitor (everolimus) improved outcomes for both the overall study population and those with ESR1 mutations after prior CDK inhibitor treatment, compared with standard care plus Afinitor. Overall survival — the time from treatment start or diagnosis until death from any cause — results were not yet mature, but a positive trend was seen, and follow-up will continue.

“These results show that the giredestrant combination provided a meaningful benefit for ER-positive breast cancer patients whose disease has progressed following treatment with a CDK inhibitor,” Levi Garraway, Roche’s chief medical officer and head of Global Product Development, said in the release. “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.”

Regarding side effects, the giredestrant combination was well tolerated, with side effects consistent with the known safety profiles of the individual drugs and no new safety concerns.

The breast cancer study is a randomized, open-label, multicenter trial. It is testing the safety and effectiveness of giredestrant combined with Afinitor compared with standard endocrine therapy combined with Afinitor in people with ER-positive, HER2-negative locally advanced or metastatic breast cancer. All patients enrolled have already been treated with a CDK4/6 inhibitor and endocrine therapy, either in the early-stage or advanced setting.

The trial’s main goals are to measure progression-free survival — the time patients live without their disease worsening or dying from any cause — in both the overall group and in those with ESR1 mutations. ESR1 mutations, which can make breast cancer resistant to hormone therapy, occur in up to 40% of people with ER-positive breast cancer after CDK4/6 inhibitor treatment. The study includes a higher number of patients with ESR1 mutations than usually seen in the general population to better understand outcomes in this group.

Other important measures include overall survival, response rates, duration of response, clinical benefit and safety.

The phase 3 study data will be submitted to health authorities in hopes of making this potential treatment option available to patients as soon as possible.

For more information on the trial, visit clinicaltrials.gov using the identification number: NCT05306340.

About giredestrant in breast cancer

Giredestrant is an investigational, oral next-generation drug known as a selective estrogen receptor degrader (SERD). It works by blocking estrogen from attaching to the ER, causing the receptor to break down and helping slow or stop cancer growth.

Giredestrant is currently being studied in five global phase 3 trials across different breast cancer stages and treatment settings to understand how it may help the widest range of patients.

Breast cancer is the most common cancer in women, with 2.3 million diagnosed and 670,000 dying from the disease each year. About 70% of cases are ER-positive, meaning the cancer cells use estrogen to grow. While treatments have advanced, ER-positive breast cancer remains difficult to manage because of its complexity, risks of disease progression, treatment side effects and resistance to endocrine therapy.

More effective options are urgently needed to delay progression and ease the burden of treatment, as per the release.

Reference

1. “Positive phase III results show Roche’s giredestrant significantly improved progression-free survival in ER-positive advanced breast cancer.” Roche. News Release. Sep. 22, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.