Ovarian Suppression With @entity19040 During Adjuvant XXXX Chemotherapy and Long-term Ovarian Function, Pregnancies, and Disease-Free Survival: A Randomized Clinical Trial.

@entity1 @entity19040 @entity0 @entity7793 @entity2670
Importance: Whether the administration of luteinizing hormone-releasing hormone analogues (LHRHa) during chemotherapy is a reliable strategy to preserve ovarian function is controversial owing to both the lack of data on long-term ovarian function and pregnancies and the safety concerns about the potential negative interactions between endocrine therapy and chemotherapy. Objective: To evaluate long-term results of LHRHa-induced @entity2670 during @entity0 chemotherapy. Design, Setting, and @entity1 : Parallel, randomized, open-label, phase 3 superiority trial conducted at 16 Italian sites. Between October 2003 and January 2008, 281 premenopausal @entity1 with stage I to III hormone receptor-positive or hormone receptor-negative @entity0 were enrolled. Last annual follow-up was June 3, 2014. Interventions: @entity1 were randomized to receive adjuvant or neoadjuvant chemotherapy alone (control group) or chemotherapy plus @entity19040 (LHRHa group). Main Outcomes and Measures: The primary planned end point was incidence of chemotherapy-induced @entity7793 . Post hoc end points were long-term ovarian function (evaluated by yearly assessment of menstrual activity and defined as resumed by the occurrence of at least 1 menstrual cycle), pregnancies, and disease-free survival (DFS). Results: A total of 281 @entity1 (median age, 39 [range, 24-45] years) were randomized. Median follow-up was 7.3 years (interquartile range, 6.3-8.2 years). The 5-year cumulative incidence estimate of menstrual resumption was 72.6% (95% CI, 65.7%-80.3%) among the 148 @entity1 in the LHRHa group and 64.0% (95% CI, 56.2%-72.8%) among the 133 @entity1 in the control group (hazard ratio [HR], 1.28 [95% CI, 0.98-1.68]; P   =   .07; age-adjusted HR, 1.48 [95% CI, 1.12-1.95]; P   =   .006). Eight pregnancies (5-year cumulative incidence estimate of pregnancy, 2.1% [95% CI, 0.7%-6.3%]) occurred in the LHRHa group and 3 (5-year cumulative incidence estimate of pregnancy, 1.6% [95% CI, 0.4%-6.2%]) in the control group (HR, 2.56 [95% CI, 0.68-9.60]; P   =   .14; age-adjusted HR, 2.40 [95% CI, 0.62-9.22]; P   =   .20). Five-year DFS was 80.5% (95% CI, 73.1%-86.1%) in the LHRHa group and 83.7% (95% CI, 76.1%-89.1%) in the control group (LHRHa vs control: HR, 1.17 [95% CI, 0.72-1.92]; P   =   .52). Conclusions and Relevance: Among premenopausal @entity1 with either hormone receptor-positive or hormone receptor-negative @entity0 , concurrent administration of @entity19040 and chemotherapy, compared with chemotherapy alone, was associated with higher long-term probability of ovarian function recovery, without a statistically significant difference in pregnancy rate. There was no statistically significant difference in DFS for @entity1 assigned to @entity19040 and those assigned to chemotherapy alone, although study power was limited. Trial Registration: clinicaltrials.gov Identifier:NCT00311636.
