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 [Ful250 + AI], fulvestrant 500 mg [Ful500], and AI) were selected. LEE + AI, Pal + AI, Ful250 + AI, and Ful500 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 Ful250 + 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. Implications: Pal + AI, LEE + AI, Ful250 + AI, or Ful500 as first-line treatment for HR+/HER2– mBC had longer PFS than AI alone. Given the lack of head-to-head clinical trials comparing the efficacy of recently approved first-line ETs for HR+/HER2– mBC, these results have important clinical implications for the treatment of HR+/HER2– mBC in the first-line setting.