Clinical Summary: 

• Design/Population: The phase 2 PREcoopERA window-of-opportunity trial randomized premenopausal patients with previously untreated ER-positive, HER2-negative early breast cancer to recieve giredestrant alone, giredestrant plus triptorelin, or anastrozole plus triptorelin.
• Key Outcomes: Giredestrant-based regimens demonstrated robust antiproliferative activity, though giredestrant alone did not match the activity of giredestrant plus triptorelin, and superiority over standard endocrine therapy was not established.
• Clinical Relevance: These findings suggest ovarian function suppression remains important for optimal endocrine response in premenopausal patients, while supporting continued development of oral SERD-based strategies.

Results from the phase 2 PREcoopERA trial demonstrated that giredestrant, an oral selective estrogen receptor degrader, shows antiproliferative activity among premenopausal patients with ER-positive, HER2-negative early breast cancer. 

These results were presented by Lajos Pusztai, MD, DPhil, Yale Cancer Center, New Haven, Connecticut, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this study, 204 previously untreated patients were randomized to receive 30 mg of once daily giredestrant either alone (n = 82) or in combination with 3.75 mg of triptorelin on day 1 (n = 80) or 1 mg of once daily anastrozole plus triptorelin (n = 42), in 28-day cycles with repeat tumor biopsies conducted on day 29. The primary end point was change in Ki67, assessed centrally on paired tumor samples. A key secondary end point was safety.

At analysis, geometric mean change in Ki67 was –79.6% in the giredestrant plus triptorelin arm and –73.7% in the anastrozole plus triptorelin arm (log difference, −0.19; 95% confidence interval [CI], −0.47 to 0.09; P = .18), indicating no statistically significant superiority. Giredestrant monotherapy achieved a geometric mean Ki67 reduction of −68.2% (log difference, 0.45) but did not meet the predefined noninferiority margin (log difference 0.40) compared with giredestrant plus triptorelin. 

Grade 3 adverse events were reported in 2.2% of patients in the giredestrant plus triptorelin arm, 4.4% of patients in the giredestrant monotherapy arm, and 4.4% of patients in the anastrozole plus triptorelin arm. Two patients in the giredestrant monotherapy arm developed ovarian cysts. No grade 4/5 events were reported.

“[Giredestrant plus triptorelin] and [giredestrant] showed robust anti-proliferative activity, though [giredestrant plus triptorelin] superiority to [anastrozole plus triptorelin] was not demonstrated,” concluded Dr Munzone. “The results support the biological activity of [giredestrant]-based [treatment] in premenopausal [patients] and inform future endocrine strategies in this setting.”

Source: 

Munzone E. A window-of-opportunity (WOO) trial of giredestrant +/- LHRH analogue vs anastrozole + LHRHa in premenopausal patients with ER+/HER2- early breast cancer: PREcoopERA. Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. LBA2.