Efficacy and safety of giredestrant (GIRE) in patients (pts) with estrogen receptor–positive, HER2-negative early breast cancer (ER+, HER2– eBC) in the phase III lidERA BC clinical trial: Results by menopausal status.

Abstract

502 Background: The lidERA BC trial (NCT04961996) demonstrated a statistically significant, clinically meaningful improvement in invasive disease-free survival (IDFS) with GIRE (a next-generation oral SERD and full ER antagonist) vs standard-of-care endocrine therapy (SOC ET) in ER+, HER2–, Stage I–III eBC (Bardia SABCS 2025). We report efficacy and safety in pre-menopausal (PRE-M) vs post-menopausal (POST-M) pts. Methods: Pts with ER+, HER2– eBC who had BC surgery and (neo)adjuvant chemotherapy (if indicated) were randomized 1:1 to once-daily 30 mg GIRE or SOC ET (anastrozole/letrozole/exemestane [aromatase inhibitors; AIs] or tamoxifen [TAM]) for 5 years (y) of treatment (tx). PRE-M pts on GIRE and on AIs received an LHRH. Results: In the efficacy-evaluable population (n = 4170), 40.7% of pts were PRE-M and 59.3% POST-M. 58.0% of pts on TAM received LHRH. PRE-M pts generally had a slightly higher baseline risk of recurrence vs POST-M pts (high risk, 70.5% vs 66.4%; medium risk, 28.4% vs 32.5%; higher use of [neo]adjuvant chemotherapy, 91.2% vs 78.9%). GIRE showed IDFS benefit and higher 3-y rates in both PRE-M and POST-M subgroups; a similar trend was observed for distant recurrence-free interval (DRFI) (Table). Adverse events (AE) were comparable in both subgroups and across txs (Table). Fewer pts discontinued GIRE due to AEs compared with pts receiving an AI, regardless of menopausal status. Discontinuation due to musculoskeletal pain occurred in 1.6% vs 4.5% of pts receiving GIRE vs AI, respectively. More pts switched to alternative ET in the SOC ET arm vs GIRE (10.1% vs 5.7%), mainly due to AEs for both arms. Conclusions: Adjuvant GIRE improved IDFS and DRFI vs SOC ET; benefit was consistent irrespective of menopausal status. PRE-M pts experienced a 42% reduction in the risk of developing metastatic disease and POST-M pts a 24% reduction. Safety was comparable between menopausal groups and there were few discontinuations, regardless of menopausal status, although PRE-M and POST-M pts receiving GIRE had fewer tx discontinuations than those receiving an AI or TAM in the PRE-M and POST-M settings. Clinical trial information: NCT04961996 . GIRE PRE-M n = 849 SOC ET PRE-M n = 838 GIRED POST-M n = 1220 SOC ET POST-M n = 1236 IDFS hazard ratio (HR) 0.65 0.74 3-yr rate, % 94.0 91.5 91.3 88.3 DRFI HR 0.58 0.76 3-yr rate, % 95.5 92.6 93.6 91.6 PRE-M n = 1672 POST-M n = 2440 Pts, % GIRE n = 840 SOC ET n = 832 SOC ET (AI) n = 563 SOC ET (TAM) n = 269 GIRE n = 1209 SOC ET n = 1231 SOC ET (AI) n = 1183 SOC ET (TAM) n = 48 All Grade/Grade 3–4 AE 95.5/18.2 95.3/17.3 96.3/16.9 93.3/18.2 94.5/20.7 93.7/18.4 94.1/18.6 85.4/14.6 AE leading to tx discontinuation 4.9 7.8 7.5 8.6 5.7 8.5 8.2 16.7 Musculoskeletal pain* 58.1 53.5 59.7 40.5 50.8 53.6 54.6 29.2 HRs are unstratified vs SOC ET. *Includes other related terms.