In the phase II acelERA BC trial reported in the Journal of Clinical Oncology, Miguel Martín, MD, PhD, and colleagues found that the selective estrogen receptor (ER) antagonist and degrader giredestrant did not significantly improve progression-free survival vs physician’s choice of endocrine therapy in previously treated patients with ER-positive, HER2-negative advanced breast cancer.
Miguel Martín, MD, PhD
Study Details
In the open-label trial, 303 post-/pre-/perimenopausal women or men with measurable disease/evaluable bone lesions and disease progression after one or two lines of systemic therapy were enrolled between November 2020 and October 2021 at sites in 17 countries. Prior fulvestrant treatment was permitted if treatment was terminated at least 28 days before random assignment. Patients were randomly assigned to receive giredestrant at 30 mg once daily (n = 151) or physician’s choice of endocrine therapy with fulvestrant or an aromatase inhibitor (ET group; n = 152). Pre-/perimenopausal women and men also received a luteinizing hormone-releasing hormone agonist. The primary endpoint was investigator-assessed progression-free survival.
Key Findings
At clinical cutoff in February 2022, median follow-up was 7.9 months. Median progression-free survival was 5.6 months in the giredestrant group vs 5.4 months in the ET group (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.60–1.10, P = .176).
In a prespecified secondary endpoint analysis according to the presence of ESR1 mutations in circulating tumor DNA (n = 252 evaluable patients), median progression-free survival was 5.3 months vs 3.5 months (HR = 0.60, 95% CI = 0.35–1.03) among 51 vs 36 patients with detectable mutations. The hazard ratio for 66 vs 76 patients with no detectable mutation was 0.88 (95% CI = 0.54–1.42). Hazard ratios favored giredestrant in the majority of subgroups examined, including among patients who had or had not received prior fulvestrant treatment.
Treatment-related grade 3 or 4 adverse events occurred in 4.0% vs 2.6% of patients, and treatment-related serious adverse events occurred in 2.0% vs 0.7%. Adverse events led to discontinuation of treatment in 1.3% vs 2.0%. Adverse events led to death in one patient in the giredestrant group (from ischemic stroke) and one patient in the ET group (from pulmonary embolism).
The investigators concluded: “Although the acelERA BC study did not reach statistical significance for its primary investigator-assessed progression-free survival endpoint, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to physician’s choice of endocrine therapy and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.”
Dr. Martín, of Hospital Gregorio Marañón, Universidad Complutense, GEICAM, CIBERONC, Madrid, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by F. Hoffmann–La Roche Ltd. For full disclosures of the study authors, visit ascopubs.org.
