Fulvestrant with or without anti‐HER2 therapy in patients in a postmenopausal hormonal state and with ER‐positive HER2‐positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG‐C06)

BACKGROUND: The role of endocrine therapy in the treatment of patients in a postmenopausal hormonal state and with estrogen receptor (ER)‐positive, human epidermal growth factor receptor 2 (HER2)‐positive advanced or metastatic breast cancer (AMBC) is unclear. METHODS: We analyzed the data from 94 patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study (UMIN000015168), a retrospective cohort study of 1072 ER‐positive AMBC patients in a postmenopausal hormonal state who received fulvestrant 500 mg (F500): (1) to compare time to treatment failure (TTF) and overall survival (OS) by treatment group, and TTF by treatment line; (2) in patients who received endocrine therapy (including F500) or anti‐HER2 therapy as initial systemic therapy before chemotherapy, to investigate relations between TTF for the first‐line therapy or time to chemotherapy (TTC) and OS; (3) to investigate factors associated with OS. RESULTS: The TTF was longer in the patients treated with F500 as first‐ or second‐line therapy (n = 20) than in those who received later‐line F500 therapy (n = 74) (6.6 vs. 3.7 months; HR, 1.98; p = 0.014). In the 59 patients who received endocrine therapy or anti‐HER2 therapy as initial systemic therapy before chemotherapy, those with TTC ≥3 years had longer median OS than those with TTC <3 years (10.5 vs. 5.9 years; HR, 0.32; p = 0.001). Longer TTC was associated with prolonged OS. CONCLUSIONS: In patients with ER‐positive HER2‐positive AMBC enrolled in the Safari study, TTF was longer in patients who received F500 as first‐ or second‐line therapy. In patients who received chemotherapy‐free initial systemic therapy, the prolonged OS in those with TTC ≥3 years suggests that this value may be a helpful cut‐off for indicating clinical outcomes.