Hope S. Rugo, MD; SABCS 2025: Selective Estrogen Degrader Giredestrant Brings Clinically Meaningful Improvements in Metastatic Breast Cancer: evERA Breast Cancer Trial

Hope S. Rugo, MD; SABCS 2025: Selective Estrogen Degrader Giredestrant Brings Clinically Meaningful Improvements in Metastatic Breast Cancer: evERA Breast Cancer Trial

An interview with:

Hope S. Rugo, MD, Director, Women’s Cancers Program; Division Chief, Breast Medical Oncology; Professor, Department of Medical Oncology and Therapeutic Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA

SAN ANTONIO, USA—Further improvements in hormone therapy for ER-positive breast cancer were on display at the San Antonio Breast Cancer Symposium where results from the Phase III evERA Breast Cancer trial were discussed.  The study investigated the use of the selective estrogen degrader agent giredestrant used together with everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancers that had previously been treated with a CDK4/6 inhibitor.

Hope S. Rugo, MD, Division Chief of Breast Medical Oncology at the  City of Hope Comprehensive Cancer Center in Duarte, California, delivered the latest findings at the conference.  Afterwards she talked with Peter Goodwin from the Audio Journal of Oncology.

Audio Journal of Oncology:  Hope S. Rugo

IN: [GOODWIN]”Peter Goodwin here with the ….

OUT:   …..thank you so much! Bye!  11:40 secs

San Antonio Breast Cancer Symposium, Abstract GS3-09:

Clinical and biomarker subgroup analysis of evERA Breast Cancer: A Phase III trial of giredestrant plus everolimus in patients with estrogen receptor-positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor.

S. Rugo; S. M. Tolaney; K. L. Jhaveri;  M. Martin;  G. A. Vidal;  L. Moscetti;  A. Brufsky;  W. J. Gradishar;  A. Schneeweiss;  N. Niikura; A. Favret;  M. Alfie;  K. S. Lee;  S. Khan;  M. Feldman;  B. M. Day;  L. H. Lam;  W. C. Darbonne;  T. M. Fernando;  P. Perez-Moreno;  E. L. Mayer

Background

The first-line standard of care (SOC) for patients (pts) with estrogen receptor-positive, HER2-negative advanced breast cancer (ER+, HER2- aBC) is CDK4/6 inhibitor (i) + endocrine therapy (ET) but effective post-CDK4/6i options remain limited. Giredestrant (GIRE) targets the ER pathway while everolimus (E) targets the PI3K/AKT/mTOR pathway; both of which are implicated in driving resistance in the post-CDK4/6i setting. evERA BC (NCT05306340) is the first Phase III trial to demonstrate statistically significant and clinically meaningful improvement in investigator-assessed progression-free survival (INV-PFS) with an all-oral selective ER antagonist and degrader combination of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET, both in pts whose tumors had a detectable ESR1 mutation (m) and in the intent-to-treat (ITT) population (Mayer ESMO 2025). The safety profile of GIRE + E was manageable with no unexpected findings (Mayer ESMO 2025). We report results from prespecified exploratory subgroup analyses.

Methods

Pts who had ER+, HER2- aBC with disease progression (PD) post-CDK4/6i + ET in the aBC setting, or relapse during/after CDK4/6i + ET in the adjuvant setting, were randomized 1:1 to once-daily oral 30 mg GIRE + 10 mg E or SOC ET (exemestane, fulvestrant, or tamoxifen) + E until PD or unacceptable toxicity. Mutational status was determined using circulating tumor DNA at baseline. The co-primary endpoints were INV-PFS per Response Evaluation Criteria in Solid Tumors v1.1 in pts whose tumors had detectable ESR1m and in the ITT population. INV-PFS was assessed by subgroup analyses.

Results

Three-hundred-and-seventy-three pts were randomized; 183 pts were randomized to GIRE + E and 190 to SOC ET + E. A total of 207 pts (55%) had tumors with ESR1m, 115 (31%) had PIK3CAm, and 137 (37%) had alterations (alt) in the PI3K pathway genes (PIK3CA/AKT1/PTEN). Sixty-four pts (17%) had both ESR1m and PIK3CAm; 76 (20%) had both ESR1m and PIK3CA/AKT1/PTEN alt. Ninety-eight percent of pts received a CDK4/6i in the metastatic setting. INV-PFS benefit was observed for GIRE + E vs SOC ET + E regardless of PIK3CAm status or PIK3CA/AKT1/PTEN alt in both the ESR1m and ITT populations (Table). Consistent benefit was observed regardless of duration of prior CDK4/6i (Table). Data for additional subgroup analyses for prior therapy will be presented.

Conclusions

GIRE + E led to clinically meaningful improvements in INV-PFS vs SOC ET + E irrespective of PIK3CAm and PIK3CA/AKT1/PTEN alt, and other key relevant subgroups, regardless of ESR1m status. These data support the use of GIRE + E vs SOC ET + E in pts with ER+, HER2- aBC post-CDK4/6i + ET.

Audio Journal of Oncology March 6th , 2026.