A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer

Background Fulvestrant, a selective estrogen receptor degrader, is approved for first- and second-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer (ABC). Methods Meta-analysis of randomized controlled trials (RCTs) evaluating fulvestrant 500 mg in postmenopausal hormone receptor-positive ABC, to evaluate differences in clinical benefit rate (CBR; proportion of patients experiencing best overall response of complete response, partial response, or stable disease for ≥ 24 weeks) between fulvestrant 500 mg and comparator endocrine therapies. Odds ratios (OR) and 95% confidence intervals (CI) for CBR were calculated; fixed effects (FE) models were constructed (first- and second-line data, alone and combined). Results Six RCTs were included. Four studies evaluated fulvestrant 500 mg vs. fulvestrant 250 mg; two evaluated fulvestrant 500 mg vs. anastrozole 1 mg. In total, 1054 and 534 patients were included (first- and second-line treatment, respectively). Analysis of OR and 95% CI of CBR by therapy line favored fulvestrant 500 mg vs. comparator therapy. Assessing all results combined in the FE model indicated significant improvement in CBR with fulvestrant 500 mg vs. comparator treatments (OR 1.33; 95% CI 1.13–1.57; p = 0.001). Restricting the FE model to therapy line demonstrated significant improvement in CBR vs. comparator treatments (OR 1.33; 95% CI 1.02–1.73; p = 0.035) for first-line, and a trend to improvement vs. comparator treatments (OR 1.27; 95% CI 0.90–1.79; p = 0.174) for second-line. Conclusions In postmenopausal patients with hormone receptor-positive ABC, fulvestrant 500 mg first-line was associated with significantly greater CBR (more patients benefiting from treatment) vs. comparator endocrine therapy.