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

Background: Luteinizing 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.

Methods: We 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.

Results: Eligible 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.

Conclusions: 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 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.

Keywords: Adjuvant endocrine therapy; Disease-free survival (DFS); Leuprorelin acetate; Premenopausal endocrine-responsive breast cancer; Safety.

Fig. 1

Patient disposition, N number of patients evaluated

Fig. 2

Kaplan–Meier analysis of disease-free survival for patients a during the overall 5-year study period and b during the third through fifth year study period. HR hazard ratio, CI confidence interval

Fig. 3

Time course of mean changes from baseline in serum estradiol levels throughout the 5-year study period. Data indicate the mean + SD. SD standard deviation, E ₂ estradiol

Fig. 4

Time course of the mean change rates from baseline in bone mineral density in the lumbar spine in patients a without or b with concomitant anti-osteoporosis treatment throughout the 5-year study period. Data indicate the mean + SD. SD standard deviation