Estrogen Receptor Antagonist Under Study for Locally Advanced or Metastatic Breast Cancer
Posted: Friday, August 6, 2021
In the nonrandomized, open-label, dose-escalation and -expansion, phase Ia/b GO39932 study, single-agent giredestrant (GDC-9545) was reported to be well tolerated at all administered doses in patients with estrogen receptor–positive, HER2-negative locally advanced or metastatic breast cancer, according to Komal L. Jhaveri, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues. These updated interim data, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 1017), also revealed clinical activity of this estrogen receptor antagonist.
“Many patients [with estrogen receptor–positive breast cancer] relapse during or after adjuvant endocrine therapy or develop resistance via ESR1 mutations that drive E-independent transcription and proliferation,” the investigators commented. “Giredestrant…is active despite ESR1 mutations.”
In this trial, patients were administered 10 (n = 6), 30 (n = 41), 90/100 (n = 51), or 250 (n = 9) mg daily of giredestrant. No adverse events led to the discontinuation of treatment, and no dose-limiting toxicities were reported; the maximum tolerated dose was not reached. Fatigue (21%), arthralgia (17%), and nausea (16%) were the most frequently reported adverse events; most were of grade 1 or 2. A total of 5% of patients experienced grade 3 treatment-related adverse events; per investigator assessment, there were no grade 4 or 5 reactions. Bradycardia was reported in 7% of patients.
The median durations of progression-free survival were 5.3, 7.2, 7.9, and 5.4 months with 10, 30, 90/100, and 250 mg of giredestrant, respectively. The clinical benefit rate was 17% with 10 mg, 48% with 30 mg, 53% with 90/100 mg, and 33% with 250 mg. The partial response rates were 17%, 5%, 10%, and 0% with 10, 30, 90/100, and 250 mg, respectively. A total of 55 cases of stable disease were reported (10 mg: 33%; 30 mg: 49%; 90/100 mg: 55%; 250 mg: 56%).
Disclosure: For full disclosures of the study authors, visit coi.asco.org.