Factors Associated with Prolonged Time to Treatment Failure with Fulvestrant 500 Mg in Patients with Postmenopausal Estrogen Receptor-Positive Advanced/metastatic Breast Cancer (JBCRG-C06; Safari): A Subgroup Analysis

Background: This subanalysis of a retrospective, multicenter, cohort study of fulvestrant 500 mg (F500) in advanced/metastatic breast cancer (AMBC) patients in Japan (UMIN000015168) sought to identify clinical factors associated with prolonged time to treatment failure (TTF). Methods: We analyzed ER+/human epidermal growth factor receptor 2 (HER2)-negative and ER+/HER2-positive patients who received F500 as 2nd- or later-line treatment. Factors investigated were age (≥65/≤65 years), treatment line (≥4th/3rd/2nd), time from AMBC diagnosis to F500 use (<3/≥3 years), prior palliative chemotherapy (no/yes), nuclear or histological grade (1/2/3), visceral metastasis (no/yes), ER expression (+/−), and progesterone receptor expression (+/−). TTF was determined using Kaplan–Meier analysis. TTF data were analyzed using univariate and multivariate analyses with a Cox proportional hazards model. Results: We registered 1072 patients who received F500 between November 2011 and December 2014 at 16 sites in Japan. In the ER+/HER2− group (n = 828), median TTF was 5.4 months. By univariate analysis, higher age, earlier F500 use and no prior chemotherapy were associated with significantly longer TTF. By multivariate analysis, higher age, longer time from AMBC diagnosis to F500 use, no prior palliative chemotherapy and F500 treatment line were correlated with prolonged TTF (Table). In the ER+/HER2+ group (n = 132), treatment line was correlated with TTF (median 4.6 months) in the univariate analysis (P = 0.042); no factors significantly correlated with TTF in the multivariate analysis.Table302P Factors correlated with TTF in ER+/HER2− AMBC patientsER+/HER2−Hazard ratio95% confidence intervalPAge (≥65/<65 years)0.850.73–0.990.035Treatment line (≥4th/3rd/2nd)1.361.22–1.52<0.001Time from diagnosis (≥3/<3 years)0.650.54–0.79<0.001Prior chemotherapy (yes/no)1.341.13–1.58<0.001 Open table in a new tab Conclusions: In ER+/HER2− patients who received F500 as a ≥ 2nd-line treatment, treatment line, advanced age, no prior palliative chemotherapy and a longer time from AMBC diagnosis to F500 use were associated with longer TTF. Clinical trial identification: UMIN000015168 Legal entity responsible for the study: Japan Breast Cancer Research Group (JBCRG) Funding: Japan Breast Cancer Research Group (JBCRG) and AstraZeneca Disclosure: H. Kawaguchi: Leadership Position/Advisory Role: Chugai, AstraZeneca. Consulting fee/honorarium: Chugai, AstraZeneca, Eisai, Kyowa Kirin, Novartis, Taiho. K. Aogi: Personal fees as honoraria: Chugai, Eisai, Sanofi, SRL, AstraZeneca, Taiho, Novartis, Daiichi Sankyo, Mochida, Ono, Otsuka, and Eli Lilly Japan, and the institution received research funds from Chugai, Eisai and Sanofi. N. Masuda: Personal fees as honoraria: Chugai Pharmaceutical and AstraZeneca, and the institution received research funds from Chugai Pharmaceutical and Eisai. T. Nakayama: Lecture's Fee: AstraZeneca, Chugai Pharmaceutical Co., Ltd. Novartis Pharma K.K. Y. Ito: Research Funds: MSD, AstraZeneca, Novartis, Parexel, Chugai, Lilly. T. Takano: Research Funds: Chugai, Takeda, Novartis. S. Saji: Honoraria from AstraZeneca, Chugai Pharmaceutical, Eisai, Novartis Pharma, and research funds from AstraZeneca and Chugai Pharmaceutical. S. Morita: Lecture's Fee and Consulting fee/honorarium: AstraZeneca. H. Yamashita: Research Funds: Taiho Pharmaceutical, Daiichi Sankyo, Chugai Pharmaceutical, Takeda Pharmaceutical. T. Yamashita: Consulting fee/honorarium: Chugai, Eisai, Novartis Pharma, Taiho, Nippon Kayaku, AstraZeneca, Takeda, Kyowa Kirin, Pfizer. Y. Yamamoto: Consulting fee/honorarium: Chugai, AstraZeneca, Novartis, Esai, KyowaHakko-Kirin, Taiho, Nipponkayaku, Takeda. S. Ohno: Consulting fee/honorarium: Chugai, AstraZeneca, Eisai, Novartis. All other authors have declared no conflicts of interest.