- A meta-analysis finds that fulvestrant plus a targeted agent is more efficacious than fulvestrant monotherapy in patients with hormone receptor (HR)-positive metastatic breast cancer (MBC) who had progressed on prior endocrine therapy.
Why this matters
- Endocrine resistance is nearly universal in MBC.
- Previous individual studies have shown conflicting results.
- Meta-analysis of phase 2 or 3 randomized controlled trials (RCTs) of fulvestrant combination therapy vs fulvestrant monotherapy (n=13 studies; 2247 patients received combination therapy, 1663 received monotherapy) after a search of PubMed, EMBASE, and Cochrane Library.
- Funding: Youth Science Foundation of Jianxi Province, China.
- Across all studies, combination therapy was superior to monotherapy:
- PFS: HR, 0.73 (95% CI, 0.63-0.86).
- Objective response rate (ORR): risk ratio (RR), 2.07 (95% CI, 1.67-2.58).
- In subgroup analysis, fulvestrant+cyclin-dependent kinase (CDK4/6) inhibitor was superior to monotherapy:
- PFS: HR, 0.51 (95% CI, 0.43-0.61).
- ORR: RR, 2.72 (95% CI, 1.93-3.83).
- In subgroup analysis, fulvestrant+PI3K/mTOR inhibitor was superior to monotherapy:
- PFS: HR, 0.73 (95% CI, 0.66-0.81).
- ORR: RR, 1.60 (95% CI, 1.15-2.23).
- In subgroup analysis, fulvestrant+other targeted therapies had no different PFS but superior ORR, 2.19 (95% CI, 1.21-3.98).
- Heterogeneity in drug doses, combination strategy, and treatment regimens.