Phase II trial of CC-486, a DNA methyltransferase inhibitor, in combination with fulvestrant in postmenopausal women with ER+, HER2- metastatic breast cancer who have progressed on an aromatase inhibitor (AI).

TPS616Background: The HR+/HER2- subtype comprises ~70% of all breast cancers. Sequential endocrine therapy with SERMS ( tamoxifen), AIs (letrozole, anastrozole, exemestane), and SERDs (fulvestrant) are recommended for pts with HR+ metastatic breast cancer (MBC). However, development of resistance to endocrine therapy poses a major problem in the use of these agents. CC-486, an oral epigenetic modifying agent, is hypothesized to potentially restore sensitivity to endocrine therapy. This Phase II study will evaluate the efficacy of CC-486 in combination with fulvestrant in pts with ER+/HER2- MBC who have progressed on an AI. Methods: Approximately 92 pts will be randomized 1:1 to receive CC-486 300 mg orally on days 1 - 21 of each 28-day cycle plus fulvestrant 500 mg IM on days 1 and 15 in the first cycle and day 1 in cycles ≥ 2 or fulvestrant 500 mg on days 1 and 15 in the first cycle and day 1 in cycles ≥ 2. Key eligibility criteria include age ≥ 18 years, postmenopausal, metastatic disease, ER+/HER2− dis...