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

Abstract

BackgroundLuteinizing hormone-releasing hormone (LH-RH) agonists provide effective adjuvant treatment for premenopausal women with endocrine-responsive breast cancer. Here, we investigated appropriate treatment durations of an LH-RH agonist, leuprorelin.MethodsWe conducted an open-label, randomized controlled pilot study to evaluate the safety and efficacy of leuprorelin subcutaneously administered every-3-months for 2 versus 3 or more, up to 5 years, together with daily tamoxifen for 5 years in premenopausal endocrine-responsive breast cancer patients. Primary endpoints were disease-free survival (DFS) and safety.ResultsEligible patients (N = 222) were randomly assigned to receive leuprorelin for either 2 years (N = 112) or 3 or more years (N = 110) with tamoxifen for 5 years after surgery. Leuprorelin treatment for 3 or more years provided no significant difference in DFS rate over 2 years: 94.1 versus 91.8 % at 144 weeks (3 years) after the second year (week 96) and 90.8 versus 90.4 % at the fifth year (week 240). The overall survival rate was 100 % for both groups during the third through fifth year study period. There were no significant differences in the incidence of adverse events (AEs) between the 2 groups: most AEs were rated grade 1 or 2.ConclusionsAdjuvant leuprorelin treatment for 3 or more years with tamoxifen showed a survival benefit and safety profile similar to that for 2 years in premenopausal endocrine-responsive breast cancer patients. No new safety signal was identified for long-term leuprorelin treatment. Longer follow-up observation is needed to determine the optimal duration of leuprorelin treatment.

Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer

“…In the current study, patients who chose GnRHa+T treatment received GnRH agonist for 2 years. Shiba et al [17] reported that adjuvant leuprorelin treatment for 3 or more years with tamoxifen showed a survival benefit and safety profile similar to that for 2 years in premenopausal patients with endocrine-responsive breast cancer in a randomized controlled study. Similar to our results, several trials using GnRH agonists for 2 years reported no differences in treatment outcomes between GnRH agonists and chemotherapy [6,13,16,18].…”

Tamoxifen Pharmacovigilance: Implications for Safe Use in the Future

“…23,30 Aromatase inhibitors come with their own set of concerns, including changes in lipid profiles that are generally considered to be small and the clinical significance is unclear. In some trials, aromatase inhibitors seem to offer more safety with regards to thrombosis, but there may be a trade off in terms of lack of cardiovascular protection offered by tamoxifen, like estrogen’s cardiovascular protective effect (outside the thrombotic effects).…”

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study

“…4) [23]. It is well recognized that serum E 2 level suppression with an LH–RH agonist can cause BMD reduction, which can be prevented or mitigated with the concomitant use of anti-osteoporosis drugs [24].…”