[12] Fulvestrant versus exemestane following prior non-steroidal aromatase inhibitor therapy: first results from EFECT, a randomized, phase III trial in postmenopausal women with advanced breast cancer.

Gradishar W, Chia S, Piccart M, on behalf of the EFECT writing committee.. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago; British Columbia Cancer Agency, Vancouver, Canada; Jules Bordet Institute, Brussels, Belgium.

Background: The third-generation, non-steroidal aromatase inhibitors (AIs; anastrozole and letrozole) are increasingly used as adjuvant and first-line advanced treatments for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As many patients subsequently progress or relapse, it is important to identify agents with efficacy following AI failure.
Materials and Methods: EFECT is a randomized, double-blind, double-dummy, multicenter, phase III trial comparing the efficacy and tolerability of fulvestrant (Faslodex) vs exemestane (Aromasin) in postmenopausal women with HR+ advanced breast cancer (ABC) progressing/recurring after prior non-steroidal AI therapy. Primary endpoint: time to progression (TTP); secondary endpoints included: objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR) [RECIST criteria] and tolerability. A fulvestrant loading-dose regimen was used (IM injection): 500 mg on Day 0, 250 mg on Days 14, 28, and 250 mg every 283days, thereafter. Exemestane 25 mg PO, was given once-daily. All patients received corresponding placebo medication. Treatment was administered until progression, death or withdrawal for any other reason.
Results: 693 women were randomized to fulvestrant (n=351) or exemestane (n=342) from August 2003 to November 2005. Overall, 60% of patients had received 2 prior endocrine therapies and 60% had visceral involvement. At the time of analysis, 288 patients (82.1%) receiving fulvestrant had progressed compared with 299 (87.4%) receiving exemestane; median TTP was 3.7months in both groups (hazard ratio: 0.963; 95% confidence intervals: 0.819, 1.133; p=0.6531).[table1]Median DoR (responding patients only) was 13.5months vs 9.8 months for fulvestrant and exemestane, respectively. Median duration of CB (retrospective analysis) was 9.3 months vs 8.3 months in the two groups. Fulvestrant and exemestane both showed good activity in patients with visceral disease (CBR 29.1% fulvestrant, 27.2% exemestane). Both treatments were very well tolerated, with no significant differences in the incidence of pre-specified adverse events (weight gain, increased appetite, hot flashes, joint disorders, nausea/vomiting, diarrhea, androgenic effects, injection-site reactions). Fulvestrant plasma level data confirm that steady state was reached within 1 month.
Conclusion: Fulvestrant loading-dose offers a potentially effective and well-tolerated treatment option for postmenopausal women with ABC who have progressed/recurred on non-steroidal AI therapy.

Friday, December 15, 2006 9:45 AM

General Session 3 (9:30 AM-11:15 AM)