Giredestrant Plus Everolimus Extends Post-CDK4/6 Inhibitor PFS, Driven by ESR1 Mutations

This phase 3 trial tests an all-oral oral SERD plus mTOR inhibitor combination against standard endocrine therapy plus everolimus after CDK4/6 inhibitor progression, and it shows that benefit concentrates in ESR1-mutated disease.

📅 Journal publication: Oct 1, 2026 · Last updated: Oct 24, 2026

giredestranteverolimusexemestanefulvestranttamoxifenoral SERDmTOR inhibitorER-positive HER2-negative advanced breast cancerESR1 mutationpost-CDK4/6 inhibitorphase 3 randomized trialoncology pharmacystomatitispneumonitis Oncology Pharmacy

Background Information

Giredestrant boosts outcomes in resistant breast cancer.

New therapeutic strategies are needed for advanced breast cancer resistant to current therapies. Giredestrant plus everolimus significantly improved progression-free survival compared to standard therapy plus everolimus, notably in ESR1-mutated tumors. The oral giredestrant-everolimus regimen offers a promising alternative for patients with resistant ER-positive, HER2-negative breast cancer. Giredestrant and everolimus show potential in improving outcomes for advanced breast cancer with ESR1 mutations.

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Authors: Mayer EL, Tolaney SM, Martín M, Vidal GA, Moscetti L, Jhaveri KL, Brufsky A, Gradishar WJ, Schneeweiss A, Niikura N, Favret A, Alfie M, Lee KS, Khan S, Feldman MB, Day BM, Lam LH, Darbonne WC, Shah MD, Griffiths KL, DiLallo G, Pérez-Moreno PD, Rugo HS, evERA Breast Cancer Investigators

Citation: Mayer EL, Tolaney SM, Martín M, et al. Giredestrant plus Everolimus in Advanced Breast Cancer. The New England journal of medicine. 2026;395(13):1285-1298. doi:10.1056/NEJMoa2602457

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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