Fulvestrant plus goserelin versus anastrozole plus goserelin versus goserelin alone for hormone receptor-positive, HER2-negative tamoxifen-pretreated premenopausal women with recurrent or metastatic breast cancer (KCSG BR10-04): a multicentre, open-label, three-arm, randomised phase II trial (FLAG study)

Abstract Background We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC). Patients and methods In this multicentre, open-label, randomised phase II study, premenopausal women aged ≥18 years with HR+, HER2–, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or G alone. The primary end-point was time to progression (TTP). Secondary end-points included overall survival, overall response rate, clinical benefit rate and toxicity. Results Of 138 eligible patients, 44 were randomly assigned to receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was 32.2 months (interquartile range: 23.69–40.86) and the median age was 43.0 years (range 23.0–55.0). The median TTP was 16.3 months (95% confidence interval [CI] 7.5–25.1) for F + G, 14.5 months (95% CI 11.0–18.0) for A + G and 13.5 months (95% CI 10.3–16.8) for G alone. Compared with G alone, the hazard ratios were 0.608 for F + G (95% CI, 0.370–0.998; p = 0.049) and 0.982 for A + G (95% CI, 0.624–1.546; p = 0.937). In terms of visceral metastasis, a stratification factor, there were no TTP differences according to treatment arm. Grade III or IV toxicities were rarely observed. Of the common adverse events, grade I arthralgia and joint stiffness were more frequently observed in the F + G than in the A + G or G-alone groups (p  Conclusions F + G provides a promising new option for the treatment of premenopausal women with HR+, HER2-, tamoxifen-pretreated MBC. Trial registration ClinicalTrials.gov number NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number BR10-04.