FDA Accepts Application for Giredestrant Combo in Advanced Breast Cancer

Genentech has announced that the U.S. Food and Drug Administration (FDA) has accepted a new drug application for giredestrant in combination with Afinitor (everolimus) to treat adult patients with certain types of advanced breast cancer.

The application seeks approval for patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated locally advanced or metastatic breast cancer whose disease returned or spread following a prior endocrine-based regimen. The FDA is expected to reach a decision regarding the approval of this oral therapy by Dec. 18, 2026.

If approved, the combination of giredestrant and Afinitor would become the first and only oral selective estrogen receptor degrader (SERD) combination therapy available for patients in the post-cyclin-dependent kinase (CDK)4/6 inhibitor setting. Estrogen receptor-positive breast cancer represents approximately 70% of all breast cancer cases. While treatments have advanced, patients often face resistance to endocrine therapies, which increases the risk of the disease progressing.

Main data that support the findings

The FDA application is supported by data from the Phase 3 evERA Breast Cancer study. The trial results showed that the combination of giredestrant and Afinitor reduced the risk of disease progression or death by 44% in the intention-to-treat (ITT) population compared with the standard-of-care endocrine therapy plus Afinitor.

In patients specifically with ESR1 mutations, the risk reduction was more pronounced. Results showed a 62% reduction in the risk of disease progression or death for this group. The study measured median progression-free survival (PFS), which refers to the length of time a patient lives with the disease without it getting worse.

In the ESR1-mutated group, the median PFS was 9.99 months for those receiving the giredestrant combination, compared to 5.45 months for those in the comparator arm. For the ITT population, the median PFS reached 8.77 months with giredestrant versus 5.49 months for those receiving the standard-of-care combination.

While data regarding overall survival (OS) were not yet mature at the time of the analysis, researchers observed a positive trend. In the ITT population, the hazard ratio for OS was 0.69, and in the ESR1-mutated population, the hazard ratio was 0.62. Researchers will continue to follow up with participants for further survival analysis.

Trial details

The evERA Breast Cancer study is a phase 3, randomized, open-label, multicenter trial. It was designed to evaluate how giredestrant performs when paired with Afinitor versus the effectiveness of standard-of-care endocrine therapy combined with everolimus.

The trial included patients with ER-positive, HER2-negative locally advanced or metastatic breast cancer. All participants had previously received treatment with a CDK4/6 inhibitor and endocrine therapy. This treatment could have been administered either in the adjuvant setting (after initial surgery) or for locally advanced or metastatic disease.

The primary goals, or endpoints, of the study were investigator-assessed PFS in both the ITT and ESR1-mutated populations. To ensure a thorough evaluation, the trial was enriched with a higher number of patients with ESR1 mutations than typically found in nature. In the post-CDK inhibitor setting, ESR1 mutations are found in up to 40% of people with ER-positive disease. Secondary goals of the study included assessing overall survival, the duration of the response to treatment, the objective response rate, and the clinical benefit rate.

Giredestrant is an investigational, oral next-generation SERD. It is designed to work as a full antagonist, meaning it blocks estrogen from binding to the receptors on cancer cells. This process triggers the breakdown, or degradation, of the receptor, which can stop or slow the growth of the cancer. Because it is an oral medication, it may minimize the impact of treatment on the lives of patients by removing the need for injections.

Safety

According to the study findings, the safety profile of the giredestrant and Afinitor combination was manageable. The adverse events reported by participants were consistent with the safety profiles already known for each individual medicine.

Researchers reported that there were no unexpected safety findings during the trial. Notably, the study found no instances of photopsia, which is a visual symptom where a person experiences perceived flashes of light. The safety assessment remains a key secondary endpoint of the trial as researchers continue to monitor the long-term effects of the combination therapy in the study population.

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.

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