Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2− early breast cancer

BACKGROUND: Current standard of care for patients with HR+/HER2- early breast cancer (EBC) includes adjuvant endocrine therapy with an aromatase inhibitor (AI) or tamoxifen (TAM). We present a trial-level meta-analysis on efficacy of AI vs TAM in patients with HR+/HER2- EBC. METHODS: A systematic literature review was conducted using key medical literature databases (eg, PubMed; inception to October 2023) and data from conferences (to December 2023). Phase 3 randomized controlled trials (RCTs) that had ≥80 % of patients with HR+/HER2- EBC (or available subgroup data) and reported a disease-free survival (DFS) hazard ratio for AI vs TAM were included in the meta-analysis, regardless of menopausal status and ovarian function suppression (OFS) use. The generic invariance method was used to calculate a pooled effect estimate of DFS hazard ratios and 95 % CIs. A base-case analysis (all RCTs) and scenario analyses for NSAI-only, premenopausal, and postmenopausal RCTs were conducted. RESULTS: Five RCTs were identified for inclusion in the meta-analysis. In the base-case analysis, DFS significantly favored AI ± OFS vs TAM ± OFS (pooled hazard ratio, 0.68; 95 % CI, 0.61-0.76; P < .0001). Results from scenario analyses were consistent with the base case; NSAI-only (pooled hazard ratio, 0.68; 95 % CI, 0.59-0.78; P < .0001), premenopausal (pooled hazard ratio, 0.65; 95 % CI, 0.56-0.76; P < .0001), and postmenopausal (pooled hazard ratio, 0.72; 95 % CI, 0.61-0.86; P = .001) RCTs favored AI ± OFS over TAM ± OFS. CONCLUSIONS: This trial-level meta-analysis demonstrated a significant DFS benefit with AI vs TAM for patients with HR+/HER2- EBC, which was more pronounced in premenopausal women.