As reported in The New England Journal of Medicine by Langley et al, a UK phase III trial (PATCH/STAMPEDE-1) has shown noninferiority in metastasis-free survival with the use of transdermal estradiol (tE2) patches vs luteinizing hormone–releasing hormone (LHRH) agonist treatment in men with locally advanced prostate cancer.
Study Details
In the multicenter open-label trial, 1,360 patients were randomly assigned between 2007 and 2022 to receive tE2 patches providing 100 μg of estradiol every 24 hours at an initial dose of four patches twice weekly (n = 721) or LHRH agonist treatment every 4 or 12 weeks (n = 639) with treatment with bicalutamide or flutamide for up to 8 weeks being permitted. The primary outcome measure was 3-year metastasis-free survival; the noninferiority margin was four percentage points, corresponding to a target hazard ratio (HR) of 1.31.
Key Findings
Metastasis-free survival at 3 years was 87.1% in the tE2 patch group vs 85.9% in the LHRH agonist group (HR = 0.96, upper limit of the one-sided 95% confidence interval [CI] = 1.11, meeting the criterion for noninferiority).
Among patients who continued assigned treatment, castrate levels of testosterone were sustained during the first year in 85% of patients in each group. Overall survival at 5 years was 81.1% in the tE2 patch group and 79.2% with the LHRH agonist group (HR = 0.90, 95% CI = 0.75–1.07).
Adverse events of grade 3 or higher occurred in 16% of the tE2 patch group and 19% of the LHRH agonist group. Hot flashes of any grade occurred in 44% of the tE2 patch group and 89% of the LHRH agonist group, with grade ≥ 2 events occurring in 8% vs 37%. Gynecomastia of any grade occurred in 85% vs 42% of patients, with grade ≥ 2 events occurring in 37% vs 9%.
The investigators concluded: “In patients with locally advanced prostate cancer, tE2 was noninferior to LHRH agonists for 3-year metastasis-free survival, with a lower incidence of hot flashes but a higher incidence of gynecomastia.”
Ruth E. Langley, FRCP, PhD, of MRC Clinical Trials Unit at University College London, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by Cancer Research U.K. and U.K. Research Institute Medical Research Council. For full disclosures of the study authors, visit nejm.com.
