Abstract P1-13-07: A phase III study of fulvestrant 500 mg versus 250 mg in postmenopausal Chinese women with advanced breast cancer and disease progression following failure on prior antiestrogen or aromatase inhibitor therapy: Supporting superior clinical benefit for the
Authors: Jiang Zefei , Zhang Qingyuan , Shao Zhimin , Shen Kunwei , Li Li , Feng Jifeng , Tong Zhongseng , Gu Kangsheng , Wang Xiaojia , Xu Binghe , Sun Guofang , Chen Huifang , Rukazenkov Yuri 
Published: May 2015

Abstract
Background: In the international Phase III COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) study, fulvestrant 500 mg was associated with significantly longer progression-free survival (PFS) over the 250 mg dose (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.68, 0.94; p=0.006) in postmenopausal women with advanced breast cancer (ABC) following failure on prior endocrine therapy. There were no clinically meaningful differences between the treatment groups in terms of the incidence or severity of adverse events. The present study was designed to compare the efficacy and safety of fulvestrant 500 mg versus 250 mg in a Chinese population for registration purposes.
Methods: This was a Phase III randomized, double-blind study in a Chinese population (ClinicalTrials.gov: NCT01300351). Postmenopausal women with estrogen receptor positive (ER+) ABC following failure on prior endocrine (antiestrogen [AO] or aromatase inhibitor [AI]) therapy were randomized 1:1 to fulvestrant 500 mg or 250 mg. Patients (pts) were stratified by post-AO/post-AI status and enrollment of post-AI pts was capped at 45%. Primary study endpoint was PFS. Consistency with the global CONFIRM study was to be concluded if the HR for the treatment comparison of PFS was &lt;1 (full analysis set; stratified log-rank test); the study was not powered to detect significant differences between treatment groups. Secondary endpoints included pharmacokinetics, ORR, CBR, DoR, DoCB, safety and tolerability.
Results: 221 pts were randomized to fulvestrant 500 mg (n=111) or fulvestrant 250 mg (n=110). 121 pts were in the post-AO subgroup and 100 pts were in the post-AI subgroup. Demographic and baseline characteristics were balanced between fulvestrant 500 mg and fulvestrant 250 mg and comparable with those in the global CONFIRM study. 98% (119/121) in the post-AO subgroup and 92% (92/100) in the post-AI subgroup had adjuvant endocrine therapy, while only 12% (14/121) in the post-AO subgroup and 51% (51/100) in the post-AI subgroup used salvage endocrine therapy. At the time of the primary analysis, 152 progression events (69%) had occurred (post-AO 59% [71/121]; post-AI 81% [81/100]). Median PFS was 8.0 months (m) in the fulvestrant 500 mg group vs 4.0 m in the 250 mg group (HR 0.75; 95% CI 0.54, 1.03; p=0.078); the predefined criterion for consistency with the global CONFIRM study was met. In a predefined subgroup analysis of PFS, the HR for fulvestrant 500 mg vs 250 mg was &lt;1 in both post-AO (median PFS 8.1 m vs 5.6 m; HR 0.86; 95% CI 0.54, 1.37) and post-AI (median PFS 5.8 m vs 2.9 m; HR 0.65; 95% CI 0.42, 1.03) subgroups. Secondary endpoints favored fulvestrant 500 mg over 250 mg, with the exception of median DoR. Safety and tolerability profiles were consistent with the known safety profile of fulvestrant.
Conclusions: Data from the present study support the superior clinical benefit of fulvestrant 500 mg vs 250 mg demonstrated in the global CONFIRM study, in postmenopausal Chinese women with ER+ ABC. Hazard ratios favoring fulvestrant 500 mg were observed in both the post-AO and post-AI settings.
Citation Format: Zefei Jiang, Qingyuan Zhang, Zhimin Shao, Kunwei Shen, Li Li, Jifeng Feng, Zhongseng Tong, Kangsheng Gu, Xiaojia Wang, Binghe Xu, Guofang Sun, Huifang Chen, Yuri Rukazenkov. A phase III study of fulvestrant 500 mg versus 250 mg in postmenopausal Chinese women with advanced breast cancer and disease progression following failure on prior antiestrogen or aromatase inhibitor therapy: Supporting superior clinical benefit for the [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-13-07.