588 Background: The aim was to provide an endocrine therapy option against advanced (ABC) or recurrent breast cancer (RBC) in premenopausal women. We conducted an exploratory phase II trial in combination with an LH-RH analogue (LH-RHa) and an aromatase inhibitor (AI) to assess the efficacy and tolerability after failure of standard LH-RHa plus tamoxifen (TAM). Methods: Premenopausal patients (pts) with ER+ and/or PgR+ ABC or RBC refractory to LH-RHa + TAM were treated with LH-RHa (goserelin: GOS) and AI (anastrozole: ANA). The primary endpoint was an objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) based on RECIST, and safety assessed using CTCAE ver. 3.0. Pts with only bone legions were assessed using the criteria by Japanese Breast Cancer Society (14th Ed.). Local assessment (CR, PR or long SD of 24 weeks or longer) was confirmed independently by two radiologists. Results: Between September 2008 and November 2010, 37 pts were enrolled at 10 clinical institutions in Japan. Eleven had recurrence either during, or within one year after the end of adjuvant GOS + TAM (including GOS + TAM followed by only TAM). The disease progressed in 26 women during GOS + TAM. Mean age and BMI were 43.5 years and 22.2 kg/m2, respectively. Thirty-five pts (94.6%) were ER+, and 36 pts (97.3%) were HER2- (one with unknown HER2 status). Non-endocrine treatment included chemotherapy (20 pts; 54%) and radiation therapy (13 pts; 35%). The viscera, soft tissue, and bones were treated in 17, 15 and 14 pts, respectively. Pts with both measurable lesions and bone metastasis, measurable lesions only, and only bone metastasis were 21 (57%), 15 (41%) and 1 (2%), respectively. ORR was 18.9% (95%CI: 8.0-35.2%, 1 CR and 6 PR cases), CBR 62.2% (23 pts, 95%CI: 44.8-77.5%), and median PFS was 7.2 months. Eight pts (21.6%) had adverse events, but none resulted in treatment discontinuation. GOS + ANA was well tolerated. Conclusions: LH-RHa (GOS) + ANA can be a subsequent endocrine treatment for premenopausal pts with ABC or RBC after failure of GOS + TAM.
Randomized Phase II, Double-Blind, Placebo-Controlled Study of Exemestane With or Without Entinostat in Postmenopausal Women With Locally Recurrent or Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Treatment With a Nonsteroidal Aromatase Inhibitor
