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evERA — Giredestrant + Everolimus, ER+/HER2− advanced breast cancer, post-CDK4/6i

Abstract: 1016 · Session: Breast Cancer—Metastatic (poster/oral presentation) · Presenter: Komal Jhaveri (Memorial Sloan Kettering Cancer Center), on behalf of evERA investigators · Conference: 2026 ASCO Annual Meeting, May 29 – Jun 2, Chicago

At a glance

  • Sponsor: Roche / Genentech
  • PI / presenter: Komal Jhaveri (MSKCC); co-authors incl. Hope S. Rugo, Sara M. Tolaney, Miguel Martín, Erica L. Mayer
  • NCT ID: NCT05306340
  • Phase: 3
  • Design: Randomized, open-label, multicenter; giredestrant + everolimus vs physician's-choice endocrine therapy (exemestane) + everolimus
  • N: ~320 randomized
  • Primary endpoint(s): Investigator-assessed PFS in ITT and in the ESR1-mutant population (co-primary)
  • Comparator: Exemestane + everolimus (standard-of-care endocrine therapy + everolimus)
  • Indication: ER+/HER2− locally advanced or metastatic breast cancer
  • Line: Post-CDK4/6 inhibitor (prior CDK4/6i + endocrine therapy)

Headline result

The ASCO 2026 presentation (Abstract 1016) reported post-progression analyses of evERA. PFS2 (progression-free survival on next-line therapy) favored giredestrant + everolimus over standard endocrine therapy + everolimus in the ITT population (median 19.0 vs 13.2 mo; HR 0.69, 95% CI 0.51–0.92) and in the ESR1-mutant subgroup (median 19.0 vs 12.5 mo; HR 0.61, 95% CI 0.40–0.93). Chemotherapy-free survival also favored the giredestrant arm (median 11.1 vs 7.9 mo; HR 0.61), with the largest benefit in ESR1-mutant patients (HR 0.46, 95% CI 0.32–0.66). These follow the previously reported (ESMO 2025) co-primary PFS results: ITT median 8.77 vs 5.49 mo (HR 0.56, 95% CI 0.44–0.71; P < .0001) and ESR1-mutant median 9.99 vs 5.45 mo (HR 0.38, 95% CI 0.27–0.54; P < .0001).

Mechanism / class

Giredestrant is an oral selective estrogen receptor degrader (SERD) and full ER antagonist. Combined with the mTOR inhibitor everolimus, the regimen targets endocrine resistance — including ESR1-mutant clones that drive resistance after CDK4/6i. The FDA accepted an NDA for giredestrant + everolimus in ESR1-mutated ER+ advanced breast cancer.

Practice-changing?

Pending. evERA is the first phase 3 to pair a next-generation oral SERD with everolimus in the post-CDK4/6i setting, and the PFS2 and chemotherapy-free-survival data strengthen the benefit signal beyond the primary PFS, particularly in ESR1-mutant disease. With an NDA under FDA review, a positive label could establish giredestrant + everolimus as a chemotherapy-sparing option after CDK4/6i, but final OS data are immature.

  • Other ASCO 2026 trials: see other ER+/HER2− post-CDK4/6i SERD trials in trials/

Sources

  • ASCO Meeting Library (Abstract 403182 / Abstract 1016): https://www.asco.org/abstracts-presentations/ABSTRACT403182
  • OncLive — PFS2 / chemotherapy-free survival: https://www.onclive.com/view/giredestrant-everolimus-drives-pfs2-chemotherapy-free-survival-benefits-in-er-her2-advanced-breast-cancer
  • CancerNetwork — PFS results: https://www.cancernetwork.com/view/giredestrant-combo-significantly-boosts-pfs-in-er-advanced-breast-cancer
  • ClinicalTrials.gov NCT05306340: https://clinicaltrials.gov/study/NCT05306340
  • The ASCO Post — primary PFS: https://ascopost.com/news/october-2025/metastatic-er-positive-her2-negative-breast-cancer-novel-treatment-combination-improves-progression-free-survival/