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

摘要: Summary 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. aim of the SoFEA trial was to assess a maximum double targeting approach steroidal anti-oestrogen fulvestrant in combination continued oestrogen deprivation. Methods In composite, multicentre, phase 3 randomised controlled done UK and South Korea, (oestrogen receptor [ER] positive, progesterone [PR] or both) were eligible if they had relapsed locally metastatic disease an NSAI (given as adjuvant at least 12 months first-line 6 months). Additionally, patients have adequate organ function WHO performance status 0–2. Participants randomly assigned (1:1:1) receive (500 mg intramuscular injection day 1, followed by 250 doses days 15 29, then every 28 days) plus daily oral anastrozole (1 mg); anastrozole-matched placebo; exemestane (25 mg). Randomisation computer-generated permuted blocks, stratification centre previous use disease. investigators aware assignment exemestane, but not placebo. primary endpoint progression-free survival (PFS). Analyses intention treat. This registered ClinicalTrials.gov, numbers NCT00253422 (UK) NCT00944918 (South Korea). Findings Between March 26, 2004, Aug 6, 2010, 723 underwent randomisation: 243 anastrozole, 231 placebo, 249 exemestane. Median PFS 4·4 (95% CI 3·4–5·4) 4·8 (3·6–5·5) those 3·4 (3·0–4·6) No difference recorded between placebo (hazard ratio 1·00, 95% 0·83–1·21; log-rank p=0·98), (0·95, 0·79–1·14; p=0·56). 87 serious adverse events reported: 36 22 29 Grade 3–4 rare; most frequent arthralgia (three group anastrozole; seven eight exemestane), lethargy (three; 11; 11), nausea vomiting (five; two; eight). Interpretation After loss response NSAIs cancer, combined deprivation no better than either alone Funding Cancer Research AstraZeneca.