A Phase II Study (FINDER 2) Comparing Three Dosing Regimens of Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer.

Abstract

Abstract Background: The Faslodex Investigation of Dose evaluation in Estrogen Receptor-positive (ER+) advanced breast cancer (FINDER) 2 study investigated the efficacy, safety, and pharmacokinetic (PK) profile of 3 fulvestrant dosing regimens in postmenopausal women with ER+ advanced breast cancer, recurring/progressing after prior endocrine therapy.Objectives: Primary: to evaluate the objective response rate (ORR). Secondary included assessment of: time to progression (TTP), clinical benefit rate (CBR), duration of response (DOR), tolerability, and PK parameters.Methods: This randomized, double-blind, parallel-group, multicenter, Phase II study, evaluated patients (pts) randomized 1:1:1 to different doses of fulvestrant: 250 mg (approved dose [AD]; given on Days 0, 28 and every 28 days thereafter), 250 mg plus loading dose (LD; 500 mg on Day 0, then 250 mg on Days 14, 28 and every 28 days thereafter), and 500 mg (high dose [HD]; Days 0, 14 and 28 and every 28 days thereafter). Treatment continued until disease progression, or until any other criterion for discontinuation was met.Results: In total, 144 pts were randomized from 34 centers in 8 countries and 143 received treatment: fulvestrant AD (n=47); LD (n=50); HD (n=46). ORRs were: 8.5% (95% confidence interval [CI] 2.4-20.4%), 5.9% (1.2-16.2%), and 15.2% (6.3-28.9%) in the AD, LD, and HD arms, respectively. CBRs were: 31.9% (95% CI 19.1-47.1%), 47.1% (32.9-61.5%), and 47.8% (32.9-63.1%) for the AD, LD, and HD arms, respectively. Median TTP was numerically longer for the HD (6.0 months) and LD (6.1 months) arms vs the AD arm (3.1 months). The low number of responders in all treatment arms prevented DOR assessment. The incidence of adverse events (AEs) was similar in all groups (76.6% AD, 72.0% LD, 69.6% HD); few pts experienced serious AEs (4 pts AD, 9 LD, 4 HD) with no clustering of event type. AEs with an incidence of ≥10% (in any arm) were back pain, arthralgia, fatigue, injection-site pain, nausea, dyspnea, cough, and hot flash. Concentrations in the AD arm approached steady state in the 3rd month of dosing and within the 1st month for LD and HD. Exposure (AUC, Cmin and Cmax) appeared to be linear across the dose range studied and, for the 250mg arms, similar to that previously reported in Western populations (Studies 9238IL/0020 & 0021).Conclusion: No statistically significant differences in efficacy could be proven between AD, LD and HD given the widely overlapping CIs for median TTP. The tolerability profile was similar across the three dosing regimens. Steady-state concentrations were achieved earlier with LD and HD. A parallel study in Japanese pts will be used for comparisons of fulvestrant efficacy and tolerability in Japanese and non-Japanese pts. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4095.