A meta-analysis of anastrozole in combination with fulvestrant in the first line treatment of hormone receptor positive advanced breast cancer

Fulvestrant is a highly active systemic therapy in patients with metastatic hormone receptor positive breast cancer. Preclinical work suggested potential synergy of fulvestrant in combination with aromatase inhibitor therapy and delayed development of endocrine resistance. The purpose of this meta-analysis is to evaluate the effectiveness of fulvestrant plus anastrozole, compared to anastrozole alone, as first line treatment of postmenopausal stage IV hormone receptor positive, HER2-negative breast cancer. The literature search was performed using PubMed, Google Scholar, Embase, ASCO, and ESMO to search for abstracts published during the last 10 years using relevant keywords. Two prospective randomized clinical trials were found to fulfill the search criteria for combination of anastrozole plus fulvestrant versus anastrozole alone. Meta-estimates were calculated by combining study estimates using the DerSimonian and Laird random effects model. The linear mixed-effects model was used to generate 95 % prediction intervals (PIs) for study-specific hazard and odds ratios. Pooled hazard ratio for progression-free survival is 0.88 (95 % CI 0.72-1.09, 95 % PI 0.65-1.21), overall survival 0.88 (95 % CI 0.72-1.08, 95 % PI 0.68-1.14) and pooled odds ratio for response rate is 1.13 (95 % CI 0.79-1.63, 95 % PI 0.78-1.65). A non-significant trend was observed with anastrozole plus fulvestrant being only marginally better than anastrozole alone in the endpoints of: progression-free survival, overall survival, and response rates. Based on these data, there is not solid evidence that the addition of fulvestrant at a dose of 250 mg monthly is better than anastrozole alone as first line therapy in women with postmenopausal hormone receptor positive breast cancer.