Giredestrant Plus Afinitor May Help Some Patients With Metastatic Breast Cancer Delay Chemotherapy

For patients living with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, staying on effective treatment and delaying chemotherapy are important goals.

New research presented at the 2026 ASCO Annual Meeting suggests that a combination of giredestrant and Afinitor (everolimus) may help some patients do both.

Investigators reported that patients who received the combination continued to benefit even after their cancer progressed and moved on to another treatment. The findings came from a post-progression analysis of the phase 3 evERA Breast Cancer trial, which enrolled patients whose disease had previously been treated with a CDK4/6 inhibitor.

"The three key takeaways from this analysis today are, one, PFS benefit with giredestrant plus [Afinitor] everolimus was sustained through the next subsequent line of therapy, and the combination showed improved progression-free survival 2 and improved chemotherapy-free survival," said study presenter Dr. Komal Jhaveri of Memorial Sloan Kettering Cancer Center.

What Did Researchers Find?

Researchers looked at whether patients could remain free from a second disease progression after moving on to another treatment. They also examined how long patients were able to avoid chemotherapy or an antibody-drug conjugate (ADC).

Among all patients in the study, those treated with giredestrant plus Afinitor experienced a 31% reduction in the risk of a second disease progression or death compared with patients who received standard endocrine therapy plus Afinitor.

The benefit appeared even greater among patients whose tumors carried an ESR1 mutation, a common resistance mutation that can develop during endocrine therapy. In this group, treatment with giredestrant plus Afinitor reduced the risk of a second progression or death by 39%.

Jhaveri noted that the benefit seen with giredestrant plus Afinitor extended beyond the initial treatment period. "PFS benefit with giredestrant plus [Afinitor] was sustained through the next subsequent line of therapy," she said.

Researchers also found that patients receiving the combination were able to delay chemotherapy longer.

In the overall study population, the median time before chemotherapy, an ADC or death was 11.1 months with giredestrant plus Afinitor compared with 7.9 months with standard therapy.

Among patients with ESR1-mutated disease, the median time before chemotherapy or an ADC was 12.6 months with giredestrant plus Afinitor compared with 8.5 months in the control group.

Why Delaying Chemotherapy Matters for Patients

Many patients with metastatic breast cancer hope to remain on endocrine-based therapies for as long as possible before needing chemotherapy.

While chemotherapy can be effective, it is often associated with additional side effects and may require more frequent clinic visits. Delaying the need for chemotherapy while maintaining disease control can help preserve quality of life and provide patients with more treatment options over time.

The findings presented at ASCO suggest that giredestrant plus Afinitor may help extend that chemotherapy-free period for some patients, particularly those with ESR1-mutated disease.

In patients with ESR1 mutations, treatment with giredestrant plus Afinitor reduced the risk of needing chemotherapy, an ADC or experiencing death by 54% compared with standard endocrine therapy plus Afinitor.

What Is an ESR1 Mutation?

ESR1 mutations can develop after exposure to endocrine therapies and are a common cause of treatment resistance in HR-positive metastatic breast cancer.

The evERA study was designed to include a large proportion of patients with ESR1-mutated tumors because previous research suggested these patients may be especially likely to benefit from giredestrant, an oral selective estrogen receptor degrader (SERD).

In earlier results from the trial, patients with ESR1-mutated tumors experienced nearly 10 months of progression-free survival with giredestrant plus Afinitor compared with about 5.5 months with standard endocrine therapy plus Afinitor.

Understanding the evERA Breast Cancer Trial

The global phase 3 evERA Breast Cancer trial enrolled 373 patients with ER-positive, HER2-negative advanced breast cancer whose disease had progressed during or after treatment with a CDK4/6 inhibitor and endocrine therapy.

Patients were randomly assigned to receive either:

• Giredestrant plus Afinitor; or
• Standard endocrine therapy (exemestane, fulvestrant or tamoxifen) plus Afinitor.

The study's primary results previously showed that giredestrant plus Afinitor significantly improved progression-free survival compared with standard therapy.

The analysis presented at ASCO focused on what happened after patients stopped study treatment and moved on to subsequent therapies.

Researchers reported that follow-up treatments were generally balanced between study groups and reflected current standards of care, suggesting that the benefits observed were unlikely to be explained by differences in later treatment.

"The subsequent therapies were generally well balanced across the treatment arms and representative of the current standard of care," Jhaveri said.

Most patients in both groups received chemotherapy as their next treatment after leaving the study. Others received endocrine therapy with or without targeted therapies, and approximately one-quarter to one-third received an ADC.

Is Giredestrant Approved for Metastatic Breast Cancer?

Giredestrant is currently an investigational medicine and is not approved by the FDA for metastatic breast cancer.

Researchers continue to evaluate the drug across multiple clinical trials, including studies involving patients with ESR1-mutated disease.

Although overall survival data from evERA remain immature, investigators reported a favorable trend for patients receiving giredestrant plus Afinitor. Median overall survival had not yet been reached in the giredestrant-plus-Afinitor arm at the time of analysis.

Jhaveri said the overall survival findings were consistent with the improvements seen in other study outcomes. "Improved PFS2 and chemotherapy-free survival were consistent with the favorable overall survival data at this interim overall survival analysis," she said.

Additional follow-up will be needed to determine whether the combination ultimately improves overall survival.

References

1. Post-progression treatment analyses of evERA Breast Cancer: A phase 3 trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor. Komal Jhaveri et al. Presented at the 2026 ASCO Annual Meeting.

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