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). (November 2018)

• Record Type: Journal Article
• Authors: Kim, Ji-Yeon; Im, Seock-Ah; Jung, Kyung Hae; Ro, Jungsil; Sohn, Joohyuk; Kim, Jee Hyun; Park, Yeon Hee; Kim, Tae-Yong; Kim, Sung-Bae; Lee, Keun Seok; Kim, Gun Min; Kim, Se Hyun; Kim, Seonwoo; Ahn, Jin Seok; Lee, Kyung-Hun; Ahn, Jin-Hee; Park, In Hae; Im, Young-Hyuck
• Is Part Of: European journal of cancer. Volume 103(2018)
• Page Start: 127
• Page End: 136
• Publication Date: 2018-11
• Subjects: Metastatic breast cancer -- Premenopausal -- Fulvestrant -- Endocrine therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2018.08.004
• Languages: English
• ISSNs: 0959-8049

Abstract

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 < 0.05, respectively). 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. Highlights: In premenopausal women with hormone receptor-positive metastatic breast cancer, hormone treatment similar to that used in postmenopausal women is the standard treatment option after tamoxifen treatment failure. In this study, fulvestrant plus goserelin (G) has better clinical outcome than G alone in premenopausal women, especially those younger than 40 years. Aromatase inhibitor with G is not superior to G alone in tamoxifen-pretreated premenopausal women.