Abstract P5-14-02: Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials

Background: While fulvestrant is approved by the United Stated Food and Drug Administration as an alternate endocrine therapy for treatment of advanced breast cancer, data on its efficacy compared to other endocrine treatments are inconsistent. Clinical markers predictive of greater benefit from fulvestrant compared to the alternate endocrine agents have not been identified. Methods: We searched the literature from inception to May, 2015 from MEDLINE, EMBASE, and major conference proceedings. We included randomized controlled trials that evaluated Fulvestrant compared to either tamoxifen or an AI. We collected the efficacy data reported as Time to Progression (TTP) or Progression Free Survival (PFS) on 7 distinct subgroup of patients from the RCTs defined by: age, time to cancer reoccurrence from primary diagnosis, presence of visceral metastasis, previous chemotherapy exposure, presence of measurable disease, hormone receptor status and, HER-2 status. Data on rates of occurrences of 9 most frequently reported adverse events were also collected from both arms of the studies. Data on both efficacy and toxicity were then weighted using generic inverse variance approach and pooled in a meta-analysis using RevMan 5.3 software. Results: We identified 8 RCTs that fulfilled our criteria and involved 4,024 patients (2,032 on fulvestrant and 1,992 on control arms). TTP/PFS was the primary endpoint in 7 out of 8 RCTs and secondary endpoint in one. Compared to an AI or tamoxifen, there was a statistically significant improvement in TTP favoring fulvestrant in patients who had visceral metastasis [Hazards Ratio (HR) 0.86; 95% Confidence Interval (CI) 0.77 to 0.96, pl0.01], measurable disease [HR 0.74; 95% CI 0.58 to 0.93, p=0.01], and HER-2 overexpression [HR 0.43; 95% CI 0.27 to 0.70, pl0.001]. Similar effect sizes were observed in a sensitivity analysis excluding the trials of combinations of fulvestrant and AI in the experimental arm. Rates of occurrences of adverse events were similar between fulvestrant and other endocrine agents. Conclusion: Patients with advanced breast cancer that have visceral disease, measurable disease, or HER-2 driven disease are likely to derive higher benefits from treatment with fulvestrant compared to tamoxifen or an AI. These results may have implications for selection of patients in the design of future clinical trials and to inform treatment decisions in clinical practice. Citation Format: Niraula S, Pitz M, Gordon V, Grenier D, Amir E, Brandes L. Clinical predictors of benefit from fulvestrant in advanced breast cancer: A meta-analysis of randomized controlled trials. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-14-02.