Anastrozole plus fulvestrant vs. anastrozole alone for hormone receptor-positive advanced breast cancer: a meta-analysis of randomized controlled trials

Background For patients with hormone receptor (HR)-positive advanced breast cancer, whether the combination of anastrozole and fulvestrant is more effective than anastrozole alone is controversial. Our meta-analysis aimed to compare the efficacy and safety of the two therapies. Methods We retrieved relevant studies in Embase, the Cochrane Library, Ovid MEDLINE, PubMed, ScienceDirect, Web of Science, Scopus, and Google Scholar. The primary outcomes were overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the disease control rate (DCR), the objective response rate (ORR), and adverse events (AEs). Results Five articles based on 4 randomized controlled trials containing 2146 patients were identified in our meta-analysis. The combination group had better efficacy in the endpoints of OS (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.74-0.99, p = 0.03) and PFS (HR 0.87; 95% CI 0.77-0.97, p = 0.02). Regarding the ORR, DCR, total AEs and grade 3-5 AEs, we found no difference between the two treatments. The combination group showed a clearly higher rate of treatment discontinuations (95% CI 1.05-3.60, p = 0.03) and AEs leading to death (95% CI 1.12-9.11, p = 0.03). The subgroup analysis of AEs showed an increased incidence of extremity or muscle pain, hematologic effects, gastrointestinal disorders, and hot flashes in the combination group. Conclusions For HR-positive advanced breast cancer patients, the combination of anastrozole and fulvestrant appears to be superior to anastrozole alone in extending PFS and OS, despite relatively serious AEs.