Progression-free Survival With First-line Endocrine-based Therapies Among Postmenopausal Women With HR+/HER2-Metastatic Breast Cancer: A Network Meta-analysis

Purpose: The comparative efficacy of endocrine based therapies (ETs) for hormone receptor-positive/human epidermal growth factor receptor 2 negative (HR+/HER2) metastatic breast cancer (mBC) is not well characterized. This network meta-analysis (NMA) synthesized available evidence on progression-free survival (PFS) with first-line ETs for postmenopausal HR+/HER2 mBC. Methods: A systematic literature review identified randomized controlled trials of first-line ETs. Pairwise hazard ratios and 95% credible intervals (CrIs) were obtained via a Bayesian NMA model. Subgroup NMAs were conducted among late progressors (disease-free interval >= 12 months from completion of [neo] adjuvant therapy with letrozole or anastrozole at the time of randomization) and de novo patients, defined as patients whose initial BC diagnosis is mBC. Findings: Five trials and 5 regimens (ribociclib + an aromatase inhibitor [AI] [LEE + AI], palbociclib + AI [Pal + AI], fulvestrant 250 mg + AI [Fu1250 + AI], fulvestrant 500 mg [Fu1500], and AI) were selected. LEE + AI, Pal + AI, Fu1250 + AI, and Fu1500 had significantly longer PFS versus AI (95% CrI upper bound <= 1). LEE + AI had a 30% and 29%, and Pal + AI had a 31% and 30%, reduced hazard of progression or death versus Fu1250 + AI and Ful500 (95% CrI upper-bound <= 1), respectively. The probability of being the most efficacious was 46% for LEE + AI and 54% for Pal + AI. In subgroup analyses among late progressors, LEE + AI had a 4% reduced hazard of progression or death versus Pal + AI but was not statistically significant. In the de novo analysis, Pal + AI and LEE + AI had a 29% and 40% reduced hazard of progression or death versus Ful500, respectively, but were not statistically significant. In both subgroup analyses, all therapies had significantly longer PFS compared with AI. (C) 2018 Elsevier HS Journals, Inc. All rights reserved.