Abstract P5-14-03: A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer

Abstract

Abstract Background A network meta-analysis (NMA) of randomized controlled trials compared overall survival (OS) and serious adverse events (SAEs) of fulvestrant 500 mg with alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. Methods Data were identified by systematic literature review. Study level hazard ratios (HRs) were obtained by modeling survival data using Weibull distribution, based on statistical and visual fit. SAEs were calculated as rate of grade 3/4 adverse events per patient year. Fixed effect Bayesian NMA were conducted for both outcomes.The base case included the following comparators of interest: anastrozole 1 mg, letrozole 2.5 mg, fulvestrant 250 mg, exemestane 25 mg, everolimus 10 mg plus exemestane 25 mg. The first three comparators were included in a subgroup analysis of treatment post-antiestrogen (antiestrogen subgroup), the last three were included in a subgroup analysis of treatment post-aromatase inhibitor (aromatase inhibitor subgroup). Results Ten studies were included; all studies reported SAEs, 7 studies reported OS. In the base case, fulvestrant 500 mg improved OS versus all comparators and in the antiestrogen subgroup versus fulvestrant 250 mg (HR 0.74; 95% credible interval [CrI] 0.56, 1.00), anastrozole (HR 0.73; 95% CrI 0.52, 1.03), and letrozole (HR 0.69; 95% CrI 0.44, 1.09). In the aromatase inhibitor subgroup, fulvestrant 500 mg improved OS versus fulvestrant 250 mg (HR 0.89; 95% CrI 0.59, 1.33) and exemestane (HR 0.93; 95% CrI 0.58, 1.47); OS for fulvestrant 500 mg versus everolimus plus exemestane was similar (HR 1.02; 95% CrI 0.62, 1.69). Decreased SAE rates were seen for fulvestrant 500 mg versus letrozole, exemestane, and everolimus plus exemestane (13.22 versus 20.65, 46.63, 67.30 events, respectively) in base case and versus fulvestrant 250 mg and letrozole (14.88 versus 15.67, 23.41 events, respectively) in the antiestrogen subgroup. NMA in the aromatase inhibitor subgroup was not performed (lack of reporting SAEs). Conclusions This analysis suggests improved efficacy for fulvestrant 500 mg versus fulvestrant 250 mg and aromatase inhibitors, similar efficacy to everolimus plus exemestane, and decreased toxicity amongst a majority of the comparators. Fulvestrant 500 mg can be considered an efficacious and better tolerated alternative endocrine treatment in this setting. Citation Format: Telford C, Jones N, Batson S. A network meta-analysis of fulvestrant 500 mg versus alternative therapies for second-line treatment of postmenopausal, estrogen receptor-positive advanced breast cancer. [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 P5-14-03.