Systematic literature review of clinical trials of endocrine therapies for premenopausal women with metastatic HR+ HER2- breast cancer

Several endocrine-based therapies have recently been evaluated as treatments for premenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC). We conducted a systematic review and assessed the feasibility of an indirect treatment comparison (ITC) to characterize the comparative efficacy of endocrine-based therapies in this setting. A systematic literature review (SLR) of Medline, EMBASE, Cochrane Library and key conferences was performed to identify randomized clinical trials (RCTs) satisfying the following criteria: (a) included pre/perimenopausal women with HR+/HER2- mBC, (b) included endocrine-based therapies, (c) reported efficacy, safety, or quality of life outcomes, and (d) was published in 2007 or later (when HER2 testing was standardized). The clinical and methodological similarities across trials were assessed to evaluate the feasibility of an ITC. Four RCTs (PALOMA-3, MONARCH-2, KCSG BR10-04 and MONALEESA-7) and eight regimens (palbociclib + fulvestrant + goserelin, fulvestrant + goserelin, abemaciclib + fulvestrant + gonadotropin-releasing hormone agonist [GnRHa], fulvestrant + GnRHa, anastrozole + goserelin, goserelin, ribociclib + NSAI/tamoxifen + goserelin and NSAI/tamoxifen + goserelin) were selected. MONALEESA-7 was the only phase 3 trial investigating endocrine-based therapies as first-line in only pre/perimenopausal women with HR+/HER2- mBC; the other three trials focused on the ET-failure setting and their pre/perimenopausal populations were relatively small. ITCs were methodologically unfeasible due to critical differences in treatment settings and lack of common comparators across trials. Therefore, we were not able to characterize the relative efficacy of the different endocrine-based therapies available in the premenopausal HR+/HER2- mBC setting. This systematic review provides a comprehensive assessment of the available trial evidence on the efficacy and safety of endocrine-based therapies for premenopausal women with HR+/HER2- mBC. Only four trials have reported relevant data in this setting, and MONALEESA-7 is currently the only trial focused on premenopausal HR+ HER2- mBC in the first-line setting.