Giredestrant (oral SERD/full ER antagonist) cuts recurrence risk in ER+/HER2– early breast cancer—benefit holds in pre- and postmenopause

Giredestrant (GIRE) is a next-generation oral selective estrogen receptor degrader (SERD) and full ER antagonist tested as 5-year adjuvant endocrine therapy in the global, randomized Phase III lidERA BC trial (NCT04961996) versus physician’s choice standard endocrine therapy (SOC ET: aromatase inhibitor [anastrozole/letrozole/exemestane] or tamoxifen), with LHRH added for premenopausal patients receiving GIRE (and for those on AIs per protocol). In the efficacy-evaluable population (n=4170; 40.7% premenopausal), GIRE improved invasive disease-free survival (IDFS) in both subgroups: premenopausal IDFS HR 0.65 with 3-year IDFS 94.0% vs 91.5%, and postmenopausal IDFS HR 0.74 with 3-year IDFS 91.3% vs 88.3%; distant recurrence-free interval (DRFI) also favored GIRE (premenopausal DRFI HR 0.58; 3-year DRFI 95.5% vs 92.6%; postmenopausal DRFI HR 0.76; 3-year DRFI 93.6% vs 91.6%). Safety was reported as comparable across menopausal status and treatments, with fewer discontinuations on GIRE than on AI regardless of menopausal status; discontinuation due to musculoskeletal pain was 1.6% with GIRE vs 4.5% with AI, and switching to alternative endocrine therapy was more common on SOC ET than GIRE (10.1% vs 5.7%, mainly AE-driven)—directionally consistent with historical early follow-up adjuvant AI vs tamoxifen trials where 3-year DFS typically landed in the high-80%s to ~90% range (e.g., ATAC ~89.4% with anastrozole and 87.4% with tamoxifen at ~33 months), though lidERA’s heterogeneous SOC mix (AI or tamoxifen, with variable ovarian suppression) complicates clean cross-trial benchmarking.