A phase II, randomized, open-label 3-arm clinical trial of fulvestrant (F) plus goserelin (G) versus anastrozole (A) plus goserelin (G) versus goserelin (G) alone for hormone receptor (HR) positive, tamoxifen (T) pretreated premenopausal women with recurrent or metastatic breast cance r(MBC) (KCSG BR10-04).
1041 Background: Endocrine therapy(ET) is the preferred treatment for HR(+) MBC. For premenopausal patients who were pretreated with T, ovarian function suppression with G ± aromatase inhibitor(A.I.) is a reasonable option. Fulvestrant yields favorable outcomes in postmenopausal women with MBC. We investigated the efficacy and safety of F+G and A+G in comparison with G alone in premenopausal women with HR(+), T-pretreated MBC. Methods: In this multicenter, open-label, randomized phase 2 study, women &gt; 18 years with HR(+), T-pretreated MBC were stratified by presence of visceral metastasis and recurrence within or after 1 year of completion of adjuvant T. Premenopausal women with T-pretreated MBC eligible for ET were randomly assigned (1:1:1) to F+G (F 500 mg IM + G 3.6 mg SC Q 4 wks), or A +G (A 1 mg P.O. qd + G 3.6 mg SC Q 4 wks) or G (G 3.6 mg SC Q 4 wks). The primary endpoint was time to progression(TTP), analyzed by intention to treat with log-rank test. Secondary endpoints included overall survival, overall response rate, clinical benefit rate and toxicities according to NCI CTCAE v3.0 (ClinicalTrials.gov, No. NCT01266213). Results: Of 138 eligible pts, 44 were randomly assigned to F+G, 47 to A+G, 47 to G. The median duration of follow-up was 28.8 months(mo) and median age was 43 (range; 23.0-55.0). The median TTP was 16.3 mo(95% C.I. 7.5-25.1) for F+G, 14.5 mo(95% C.I. 11.0-18.0) for A+G, and 13.5 mo(95% C.I. 10.3-16.8) for G alone, respectively. For the comparison of each experimental arm to control arm, 24-mo TTP were analyzed: F+G vs G(%±SE): 40.5±7.5 vs. 25.3±7.0, one-sided P = 0.048, A+G vs G(%±SE): 23.9±7.2 vs. 25.3±7.0, one-sided P = 0.304. Grade 3/4 toxicities were rarely observed. Most common adverse events were grade 1 joint stiffness and arthralgia which were more frequently observed in F+G compared to A+G and G (P = 0.018 and 0.015, respectively). Conclusions: The combination of F+G as well as G ±A.I. might be a valid option for HR(+) premenopausal women with T-pretreated MBC and further investigation is warranted. Clinical trial information: NCT01266213.