Abstract OT1-1-11: The B-YOND study: A phase II three-arm randomized trial of the combination of tamoxifen plus goserelin acetate with BYL719 or buparlisib (BKM120) in premenopausal patients with hormone receptor-positive/HER2-negative locally advanced or metastatic breast
Authors: Lu Yen-Shen , Park Yeon Hee , Shao Zhimin , Valenti Roberta 
Published: May 2015

Background:

The incidence of breast cancer (BC) has been rapidly increasing in many countries in the last decades. In contrast to Western countries, approximately 50% of BC patients in Eastern countries are premenopausal, with hormone receptor-positive (HR+) disease, or luminal subtype by molecular classification. Benefit from the most recent advances in endocrine treatments for patients with HR+ BC is currently confined to postmenopausal women. For premenopausal metastatic BC (MBC) tamoxifen and/or ovary ablation/suppression remain the recommended first-line therapies for metastatic disease through category 2 evidence, calling for further clinical investigations.

In the context of growing evidence of the role of PI3K/AKT/mTOR pathway inhibition in enhancing and extending the benefit of endocrine therapies in HR+ MBC pre-clinical and clinical models, the B-YOND study is a phase II, three-arm randomized trial aimed at exploring the PI3K inhibitors buparlisib and BYL719 in combination with tamoxifen in the context of ovarian suppression in premenopausal patients with MBC.

Design & Objectives:

Premenopausal women with HR+/HER2-negative locally advanced or MBC who a) are newly diagnosed or b) recurred during or after adjuvant treatment with tamoxifen monotherapy, and received no endocrine treatment in the metastatic setting, will be randomized to receive tamoxifen plus goserelin (control arm, Arm 3) or the same combination with buparlisib (Arm 2) or BYL719 (Arm 1) until progression. Stratification based on previous treatment with tamoxifen and presence of liver and/or lung metastasis will be applied. Primary objective is the efficacy comparison of Arm 1 vs Arm 3 and Arm 2 vs Arm 3 in terms of 9-month progression free survival (PFS) rate. Secondary objectives include additional efficacy evaluations (median PFS, overall response rate, clinical benefit), safety and tolerability, quality of life, and pharmacokinetics.

Statistical Methods:

Based on previous reports, the estimated proportion of patients who are alive without progression at 9 months is 50% for the control arm (P0=0.50), and we hypothesize that this proportion is 75% for both experimental arms (P1=0.75). Using a two-sided 0.05 level of significance for both the comparisons [Arm 1 vs Arm 3; Arm 2 vs Arm 3], with an overall type-I error not greater than 0.10, with 80% power, the estimated patient numbers needed is 58 patients for each arm. With an assumption that approximately 10% patients will be lost to follow-up, a total of 192 patients will need to be randomized to the three treatment arms in 1:1:1 ratio.

Accrual

This study will be open for recruitment in Taiwan, South Korea, China, Hong Kong and Thailand and potentially extended to additional Eastern countries. Enrollment started in May 2014 and will last for an estimated period of 18 months.

Citation Format: Yen-Shen Lu, Yeon Hee Park, Zhimin Shao, Roberta Valenti. The B-YOND study: A phase II three-arm randomized trial of the combination of tamoxifen plus goserelin acetate with BYL719 or buparlisib (BKM120) in premenopausal patients with hormone receptor-positive/HER2-negative locally advanced or metastatic breast [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT1-1-11.