Giredestrant Plus Afinitor Delays Need For Chemotherapy in Breast Cancer

Treatment with giredestrant plus Afinitor (everolimus) helped patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer live longer without their cancer worsening after additional treatment and delayed the need for chemotherapy compared with standard endocrine therapy plus Afinitor, according to new findings from the phase 3 evERA BC trial presented at the 2026 ASCO Annual Meeting.

The analysis focused on outcomes after patients' disease progressed and they received subsequent treatment. Researchers found that patients who received giredestrant plus Afinitor experienced a median progression-free survival after next-line therapy (PFS2) of 19.2 months compared with 13.17 months for those who received standard endocrine therapy plus Afinitor.

PFS2 measures the time from the start of treatment until disease progression after a patient's next treatment or death. This endpoint helps researchers understand whether the benefits of a treatment continue even after patients move on to additional therapies.

Patients who received giredestrant plus Afinitor also remained free from chemotherapy longer. Median chemotherapy-free survival was 11.1 months compared with 7.89 months for patients who received standard endocrine therapy plus Afinitor.

Researchers reported that patients receiving giredestrant plus Afinitor had a 31% lower risk of disease progression after next-line therapy or death and a 39% lower risk of needing chemotherapy or dying compared with those receiving standard endocrine therapy plus Afinitor.

Lead study author Dr. Komal Jhaveri noted that treatments received after disease progression were generally similar between the study groups and reflected current standards of care. The post-progression findings were also consistent with encouraging overall survival results seen in the ongoing analysis.

Earlier Trial Results Showed Improved Disease Control

The evERA BC 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 plus endocrine therapy.

Patients were randomly assigned to receive either oral giredestrant plus Afinitor or one of several standard endocrine therapy options — exemestane, fulvestrant or tamoxifen — plus Afinitor.

The trial's primary endpoint was progression-free survival (PFS), which measures the length of time a patient lives without their cancer growing or spreading.

Results previously presented at the 2025 ESMO Congress showed that patients receiving giredestrant plus Afinitor experienced a median PFS of 8.77 months compared with 5.49 months for those receiving standard endocrine therapy plus Afinitor.

Among patients whose tumors carried an ESR1 mutation, a genetic change that can contribute to resistance to endocrine therapy, median PFS was 9.99 months with giredestrant plus Afinitor compared with 5.45 months with standard treatment.

Benefits Seen in Patients With and Without ESR1 Mutations

In the new analysis, benefits were observed regardless of ESR1 mutation status.

Among patients with ESR1-mutant tumors, median PFS2 was 19.2 months with giredestrant plus Afinitor compared with 12.54 months with standard endocrine therapy plus Afinitor. Researchers reported a 39% lower risk of disease progression after next-line therapy or death in this group.

For patients without a detected ESR1 mutation, median PFS2 was 17.25 months with giredestrant plus Afinitor compared with 12.59 months with standard endocrine therapy plus Afinitor.

The delay in chemotherapy was particularly notable among patients with ESR1-mutant disease. These patients experienced a median chemotherapy-free survival of 12.59 months compared with 8.54 months with standard endocrine therapy plus Afinitor, representing a 54% lower risk of requiring chemotherapy or dying.

Among patients without a detected ESR1 mutation, median chemotherapy-free survival was 9.53 months with giredestrant plus Afinitor compared with 7.29 months with standard treatment.

Researchers also reported updated interim overall survival data. Overall survival measures the length of time patients remain alive after starting treatment. At the time of the analysis, median overall survival had not yet been reached in the giredestrant arm, meaning more than half of patients were still alive. In the standard endocrine therapy arm, median overall survival was 26.87 months.

Safety Findings

The safety profile of giredestrant plus Afinitor was reported to be manageable and consistent with the known side effects of each treatment.

The most common side effects in the giredestrant and standard treatment groups, respectively, were stomatitis, or inflammation and sores in the mouth (47.2% versus 48.9%), diarrhea (26.9% versus 22.6%) and anemia (23.6% versus 21%).

Slow heart rate occurred in 3.8% of patients receiving giredestrant plus Afinitor and 0.5% of those receiving standard endocrine therapy plus Afinitor. No cases of photopsia, or flashes of light in vision, were reported.

Treatment was discontinued because of side effects in 17% of patients receiving giredestrant plus Afinitor and 11.8% of those receiving standard endocrine therapy plus Afinitor.

References

1. “Post-progression treatment analyses of evERA Breast Cancer (BC): a phase III trial of giredestrant (GIRE) + everolimus (E) in patients with ER-positive, HER2-negative advanced BC previously treated with a CDK4/6 inhibitor” by Dr. Komal Jhaveri, et al., presented at the 2026 ASCO Annual Meeting.
2. “Giredestrant (GIRE), an oral selective oestrogen receptor (ER) antagonist and degrader, + everolimus (E) in patients (pts) with ER-positive, HER2-negative advanced breast cancer (ER+, HER2– aBC) previously treated with a CDK4/6 inhibitor (i): Primary results of the phase III evERA BC trial” by Dr. Erin Mayer, et al., presented at the 2025 ESMO Congress.

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