Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial
Fulvestrant plus anastrozole or placebo versus exemestane alone after progression on non-steroidal aromatase inhibitors in postmenopausal patients with hormone-receptor-positive locally advanced or metastatic breast cancer (SoFEA): a composite, multicentre, phase 3 randomised trial
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DOI：
10.1016/s1470-2045(13)70322-x
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发表时间：
2013-09-01
期刊：
影响因子：
51.1
通讯作者：
Bliss, Judith M.
中科院分区：
文献类型：
--
作者：
Johnston, Stephen R. D.;Kilburn, Lucy S.;Bliss, Judith M.
背景 对于使用非甾体芳香酶抑制剂 (NSAI) 治疗后进展的晚期激素受体阳性乳腺癌绝经后妇女的最佳内分泌治疗尚不清楚。 SoFEA 试验的目的是评估类固醇抗雌激素氟维司群与持续雌激素剥夺相结合的最大双内分泌靶向方法。 方法 在英国和韩国进行的一项综合、多中心、3 期随机对照试验中，患有激素受体阳性乳腺癌（雌激素受体 [ER] 阳性、孕激素受体 [PR] 阳性或两者）的绝经后妇女符合资格，如果她们接受 NSAI（作为辅助治疗至少 12 个月或作为一线治疗至少 6 个月）后出现局部晚期或转移性疾病复发或进展。此外，患者必须有足够的器官功能，并且 WHO 体能状态为 0-2。参与者被随机分配（1:1:1）接受氟维司群（第1天肌肉注射500毫克，随后第15天和第29天250毫克剂量，然后每28天一次）加每日口服阿那曲唑（1毫克）；氟维司群加阿那曲唑匹配的安慰剂；或每日口服依西美坦（25 毫克）。随机化是通过计算机生成的排列块进行的，分层是根据中心和之前使用 NSAI 作为辅助治疗或局部晚期或转移性疾病的情况进行的。参与者和研究人员知道分配到氟维司群或依西美坦，但不知道分配到阿那曲唑或安慰剂。主要终点是无进展生存期（PFS）。分析是按意向治疗进行的。该试验已在 ClinicalTrials.gov 注册，编号为 NCT00253422（英国）和 NCT00944918（韩国）。结果 2004 年 3 月 26 日至 2010 年 8 月 6 日期间，723 名患者接受了随机分组：243 名患者被分配接受氟维司群加阿那曲唑治疗，231 名患者被分配接受氟维司群加安慰剂治疗，249 名患者被分配接受氟维司群联合安慰剂治疗。依西美坦。分配至氟维司群加阿那曲唑的患者的中位 PFS 为 4.4 个月（95% CI 3.4-5.4），分配至氟维司群加安慰剂的患者为 4.8 个月（3.6-5.5），分配至依西美坦的患者为 3.4 个月（3.0-4.6）。分配至氟维司群加阿那曲唑组和氟维司群加安慰剂组的患者之间（风险比1.00，95% CI 0.83-1.21；对数秩p = 0.98），或分配至氟维司群加安慰剂和依西美坦组的患者之间（0.95，0.79-1.14；对数秩p = 0.56），没有记录到差异。报告了 87 例严重不良事件：36 例为氟维司群加阿那曲唑组患者，22 例为氟维司群加安慰剂组患者，29 例为依西美坦组患者。 3-4 级不良事件很少见；最常见的是关节痛（氟维司群加阿那曲唑组中 3 例；氟维司群加安慰剂组中 7 例；依西美坦组中 8 例）、嗜睡（3 例；11 例；11 例）和恶心或呕吐（5 例；2 例；8 例）。 250 mg 氟维司群联合雌激素剥夺并不比单独使用氟维司群或依西美坦更好。
Background The optimum endocrine treatment for postmenopausal women with advanced hormone-receptor-positive breast cancer that has progressed on non-steroidal aromatase inhibitors (NSAIs) is unclear. The aim of the SoFEA trial was to assess a maximum double endocrine targeting approach with the steroidal anti-oestrogen fulvestrant in combination with continued oestrogen deprivation.Methods In a composite, multicentre, phase 3 randomised controlled trial done in the UK and South Korea, postmenopausal women with hormone-receptor-positive breast cancer (oestrogen receptor [ER] positive, progesterone receptor [PR] positive, or both) were eligible if they had relapsed or progressed with locally advanced or metastatic disease on an NSAI (given as adjuvant for at least 12 months or as first-line treatment for at least 6 months). Additionally, patients had to have adequate organ function and a WHO performance status of 0-2. Participants were randomly assigned (1:1:1) to receive fulvestrant (500 mg intramuscular injection on day 1, followed by 250 mg doses on days 15 and 29, and then every 28 days) plus daily oral anastrozole (1 mg); fulvestrant plus anastrozole-matched placebo; or daily oral exemestane (25 mg). Randomisation was done with computer-generated permuted blocks, and stratification was by centre and previous use of an NSAI as adjuvant treatment or for locally advanced or metastatic disease. Participants and investigators were aware of assignment to fulvestrant or exemestane, but not of assignment to anastrozole or placebo. The primary endpoint was progression-free survival (PFS). Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, numbers NCT00253422 (UK) and NCT00944918 (South Korea).Findings Between March 26, 2004, and Aug 6, 2010, 723 patients underwent randomisation: 243 were assigned to receive fulvestrant plus anastrozole, 231 to fulvestrant plus placebo, and 249 to exemestane. Median PFS was 4.4 months (95% CI 3.4-5.4) in patients assigned to fulvestrant plus anastrozole, 4.8 months (3.6-5.5) in those assigned to fulvestrant plus placebo, and 3.4 months (3.0-4.6) in those assigned to exemestane. No difference was recorded between the patients assigned to fulvestrant plus anastrozole and fulvestrant plus placebo (hazard ratio 1.00, 95% CI 0.83-1.21; log-rank p = 0.98), or between those assigned to fulvestrant plus placebo and exemestane (0.95, 0.79-1.14; log-rank p = 0.56). 87 serious adverse events were reported: 36 in patients assigned to fulvestrant plus anastrozole, 22 in those assigned to fulvestrant plus placebo, and 29 in those assigned to exemestane. Grade 3-4 adverse events were rare; the most frequent were arthralgia (three in the group assigned to fulvestrant plus anastrozole; seven in that assigned to fulvestrant plus placebo; eight in that assigned to exemestane), lethargy (three; 11; 11), and nausea or vomiting (five; two; eight).Interpretation After loss of response to NSAIs in postmenopausal women with hormone-receptor-positive advanced breast cancer, maximum double endocrine treatment with 250 mg fulvestrant combined with oestrogen deprivation is no better than either fulvestrant alone or exemestane.