Dr Mayer on Efficacy Data With Giredestrant Plus Everolimus in ER+/HER2– Breast Cancer

"What we found in the evERA study was that…in the ESR1-mutant population, patients receiving giredestrant and everolimus had a statistically significant and very clinically meaningful improvement in the primary end point of PFS."

Erica L. Mayer, MD, MPH, director of Breast Cancer Clinical Research and institute physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed primary efficacy findings from the phase 3 evERA trial (NCT05306340) evaluating the combination of the oral selective estrogen receptor degrader (SERD) giredestrant and everolimus (Afinitor) for patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer previously treated with a CDK4/6 inhibitor.

Findings presented at the 2025 ESMO Congress showed that giredestrant plus everolimus significantly reduced the risk of progression or death compared with standard-of-care (SOC) endocrine therapy plus everolimus. The evERA study met both of its primary end points by prolonging progression-free survival (PFS) in both the intent-to-treat (ITT) population and the ESR1 mutant population.

In the ITT population, the median PFS was 8.77 months (95% CI, 6.60-9.59) with the giredestrant combination compared with 5.49 months (95% CI, 4.01-5.59) for SOC (HR, 0.56; 95% CI, 0.44-0.71; P < .0001). The benefit was more pronounced in the subpopulation harboring the ESR1 mutation, where the combination elicited a median PFS of 9.99 months (95% CI, 8.08-12.94) compared with 5.45 months (95% CI, 3.75-5.62) for SOC (HR, 0.38; 95% CI, 0.27-0.54; P <.0001). Mayer noted that for the ESR1 mutant group, this represented a 62% improvement compared to the control arm.

Notably, the PFS benefit was also observed in the ITT and ESR1-mutated populations irrespective of endocrine therapy backbone used in the SOC arm.

Mayer noted that the totality of the data supports that the benefit of this combination is present for the ITT population. Although an exploratory subgroup analysis of the ESR1-negative population showed no difference in PFS between the 2 arms, it did present intriguing signals for improved response rate, duration of response, and a favorable overall survival trajectory. Furthermore, exploratory analysis found that PFS rates were similar regardless of whether the SOC arm utilized exemestane or fulvestrant.

Disclosures: Mayer reports receiving honoraria for consulting/advisory roles for AstraZeneca, Atkis, Genentech, Inc., Lilly and Novartis; research support in the form of third-party medical writing assistance for this presentation, furnished by Bena Lim, PhD, of Nucleus Global, an Inizio Company, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Reference

Mayer E, Tolaney SM, Martin M, et al. 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. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA16.