CONFIRM: A Phase III, Randomized, Parallel-Group Trial Comparing Fulvestrant 250 mg vs Fulvestrant 500 mg in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer.

Abstract

Abstract Background: Fulvestrant (Faslodex®) is an estrogen-receptor (ER) antagonist licensed for the treatment of postmenopausal women with advanced breast cancer who have progressed or recurred following prior endocrine therapy. The efficacy of fulvestrant at the approved dose (250 mg/month; F250) is well established; however, increasing the dose to 500 mg (500 mg i.m. on Day 0, then 500 mg i.m. on Days 14 and 28 and every 28 days thereafter; F500) may further improve clinical outcome. Data from the NEWEST and FIRST studies have suggested improved biological and clinical activity for F500 in the neoadjuvant and 1st-line advanced disease settings respectively. Further data are required to clarify the clinical role of F500 in ER+ advanced breast cancer.Methods: CONFIRM (COmparisoN of Faslodex In Recurrent or Metastatic breast cancer) is a randomized, double-blind, parallel-group, multicenter, Phase III study (9238IL/0064; NCT00099437) comparing F250 with F500 in postmenopausal women with ER+ advanced disease recurring or progressing after prior endocrine therapy (anti-estrogen or aromatase inhibitor). Eligible patients (pts) were randomized 1:1 to F250 or F500, and assessed for tumor progression every 12 weeks. The primary objective was to compare the efficacy of F250 and F500 in terms of time to progression (TTP). Secondary objectives included: objective response rate (ORR), clinical benefit rate (CBR; complete or partial response or stable disease lasting ≥24 weeks), duration of clinical benefit (DoCB)(all by modified RECIST criteria), overall survival and quality of life (QoL). Safety and tolerability were also assessed. Treatment with fulvestrant continued until disease progression, or discontinuation for any other reason. All patients were followed up for disease progression and survival, regardless of treatment discontinuation, unless consent was withdrawn.Results: In total, 736 women (median age 61.0yrs) were recruited between Feb '05 and Aug '07 from 128 centers in 17 countries (F500: n=362; F250: n=374). TTP was significantly longer for F500 vs F250 (HR 0.80 [95% CI: 0.68, 0.94]; p=0.006), corresponding to a 20% reduction in risk of progression. The treatment effect was consistent for all predefined subgroups analysed. ORR was similar for F500 and F250 (13.8% vs 14.6%; odds ratio 0.94 [95% CI 0.57, 1.55]; p=0.795). There was a numerical advantage in CBR for pts receiving F500 vs F250 (45.6% vs 39.6%; odds ratio 1.28 [95% CI 0.95, 1.71]; p=0.1) and in DoCB (16.6 vs 13.9 months for F500 [n=165] and F250 [n=148] respectively). There was a trend for improved overall survival for pts treated with F500 compared with F250 (HR 0.84 [95% CI: 0.69, 1.03] p=0.091). QoL (n=145) was similar for both arms. F500 was well tolerated, with a safety profile consistent with that of F250 and no evidence of dose-dependence for any AE.Discussion: The CONFIRM trial has shown a statistically significant increase in TTP for F500 compared with F250, without increase in toxicity. This translates into a clinically meaningful advantage for F500 over F250. We anticipate that the 500mg regimen will become the established dose for fulvestrant. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 25.