A follow-up study of a randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-month depot for 2 versus 3 or more years with tamoxifen for 5?years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer

摘要

Background Previously, we conducted the 5-year open-label, randomized controlled trial (RCT) of leuprorelin adjuvant therapy in post-operative premenopausal patients with endocrine-responsive breast cancer, which was a pilot study to investigate the optimal duration of leuprorelin treatment. Since, however, long-term outcomes became required for the adjuvant endocrine therapy, we performed this follow-up observation study. Methods Follow-up observation study was performed up to 10th year after randomization, continuing RCT to evaluate the efficacy and safety of leuprorelin every 3?months for?≥?3 versus 2?years, with daily tamoxifen for 5?years. Primary endpoints were disease-free survival (DFS) and 2-year landmark DFS. Results Eligible patients ( N ?=?222) were randomly assigned to receive leuprorelin for either 2?years ( N ?=?112) or?≥?3?years ( N ?=?110) with tamoxifen. Leuprorelin treatment for?≥?3?years versus 2?years provided no significant difference in DFS (HR 0.944, 95% CI 0.486–1.8392) or 2-year landmark DFS ( N ?=?99 and 102 in 2-year and?≥?3-year groups, HR 0.834, 0.397–1.753). In small, higher-risk subgroup ( n ?=?17); however, 2-year landmark DFS in?≥?3-year group was significantly longer (HR 0.095, 0.011–0.850) than that in 2-year group. The incidence of bone-related adverse events was around 5% in both groups. Conclusions Adjuvant leuprorelin treatment for?≥?3?years with tamoxifen only showed similar efficacy and safety profiles to those for 2?years in analyses among all patients but suggested greater benefit in higher-risk patients. No new safety signal was identified for long-term leuprorelin treatment. Trial registration number Not applicable. This was an observational study.