Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer according to prior therapy.

Abstract

e11528 Background: Hormone therapy (HT) is limited by the onset of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) with the ER antagonist Fulvestrant (F) can overcome this resistance. The aim of this study was to evaluate the efficacy and tolerability of F in postmenopausal women with hormone-responsive (HR) metastatic breast cancer (MBC) previously treated with Tamoxifen (T) or Aromatase Inhibitors (AI). Methods: From May 2006 to July 2008 83 patients with HR MBC progressing after T or AI for adjuvant or metastatic disease receiving F 250 mg/month were identified. Median time to progression (TTP), overall survival (OS), clinical benefit rate (CBR) defined as the proportion of partial or complete responses (CR, PR) or stable disease (SD) lasting ‡6 months were analyzed. Results: Six, 32, 33 and 12 patients received F as 1st, 2nd, 3rd and 4thline of HT for MBC, respectively. Fulvestrant resulted in an overall CBR of 38.6% (32/83) with 0% CR, 9% PR, 30%SD, 56% PD. Disease was not evaluable in 4.8% of cases. Median TTP to F was 4.9 months (4 - 5.8; 95% C.I.) and OS was 20.1 months (15.8 - 24.4; 95% C.I.). Patients with visceral metastases and with more advanced lines of overall therapy had worse outcome (OR 3.13, 1.17-8.37, 95% C.I.; p 0.023 and OR 0.72, 0.54-0.96, 95% C.I.; p 0.025, respectively). However, Fulvestrant showed activity up to the fourth line of endocrine therapy regardless of number of metastatic sites and previous AI or T therapy. Overall treatment was well tolerated. Arthralgia, swelling, and myalgia were the most common adverse all were grade 1 or 2. No injection-related adverse events were reported. Conclusions: Fulvestrant is an active treatment in HR MBC previously challenged with HT. Safety profile is optimal and it may be a suitable option in extensively pre-treated patients. Further exploration of its use in this patient population is warranted.