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

Abstract

BackgroundLeuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer.MethodsThis was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48.ResultsIn total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2 suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval −5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2 suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed.ConclusionsTAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).

Chemoprevention Agents to Reduce Mammographic Breast Density in Premenopausal Women: A Systematic Review of Clinical Trials

“…Adverse events were reported in 4 studies, although only 3 actively and systematically monitored for them. Although some studies did not assess for side effects of the interventions such as tamoxifen and leuprolide acetate, its use in other studies has been associated with vasomotor symptoms, menstrual abnormalities, uterine cancer, and thromboembolic phenomena ( 64 , 65 ). Goserelin was associated with vasomotor symptoms and sexual dysfunction, as well as weight gain and headaches ( 29 ).…”

Effectiveness of a 6-Month 22.5-mg Leuprolide Acetate Depot Formulation With Tamoxifen for Postoperative Premenopausal Estrogen Suppression in Hormone Receptor-Positive Breast Cancer

“…( 18 ) compared 6M and 3-month LHRHa treatments in a phase III, randomized, open-label, parallel-group comparative study. The E2 suppression rate was 97.6% and 96.4% in a total of 167 patients treated for 6 (n=83) and 3 (n=84) months, respectively, and there was no difference in the safety profiles or tolerability ( 18 ). In contrast to chemotherapy, LHRHas have no direct cytotoxicity, and their primary function is OFS.…”

Long-Acting Luteinizing Hormone-Releasing Hormone Agonist for Ovarian Hyperstimulation Induced by Tamoxifen for Breast Cancer

“…The 3-month depot formulation of 11.25 mg leuprorelin acetate produced similar pharmacodynamic effects of hormonal suppression to those achieved with monthly injections of 3.75 mg leuprorelin acetate [ 19 ]. Three-month depot leuprorelin with oral tamoxifen can suppress serum estradiol to the menopausal level within 4 weeks after injection in premenopausal women [ 20 ]. In the present case, after treatment with 3-month depot LHRH agonist, ovarian cysts and increased estrogen levels disappeared within 2 months.…”