Abstract OT2-05-01: FAMILY: A randomized, multicenter, open-label, phase III trial of fulvestrant versus capecitabine as maintenance therapy after first-line combination chemotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer
Authors: Yao H , Wu W , Ding L , Yu Y , Wang Y , Zeng Y , Zhao J , Li Q 
Published: May 2019

Background: Metastatic breast cancer (MBC) is incurable. Although first-line endocrine therapy is preferred to hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) MBC, combination chemotherapy should be reserved as the initial treatment for patients with rapid clinical progression, life-threatening visceral metastases, and need for rapidly symptom control. Either prolonged chemotherapy or endocrine therapy may be used as maintenance after disease control. However, which maintenance strategy is superior in terms of delaying disease progression as well as maintaining quality of life (QOL) remains uncertain. This phase III trial aims to compare the efficacy and safety of fulvestrant or capecitabine as maintenance therapy after first-line combined chemotherapy in HR+/HER2- MBC.

Trial Design: FAMILY is a multicenter, randomized, open-label phase III trial for HR+ and HER2- MBC. Eligible participants are randomized (1:1) to receive capecitabine (2000mg/m2 twice daily x 14 days followed by 7 days off) or fulvestrant (500mg Days 0, 14, 28, then every 28 days) until disease progression, unacceptable toxicity, or patient refusal. Stratification factor for randomization is sensitivity to adjuvant hormonal therapy (disease-free interval ≤24 months vs. &gt;24 months).

Eligibility Criteria: Eligible patients must have HR+ (ER and/or PR&gt;1%, by IHC) and HER2- MBC; achieved a complete or partial response or stable disease (investigator assessed) after 4-8 cycles of first-line combination chemotherapy. Patients with central nervous system metastasis and/or prior use of endocrine therapy for advanced breast cancer are excluded.

Specific Aims: The primary endpoint is progression free survival (PFS). Secondary endpoints include overall survival, overall response rate, disease control rate, safety and QOL. A prospective translational research is also planned to assess the correlations between biomarkers and response.

Statistical Design: The planned sample size of 256 patients provides approximately 80% of power to detect a 6 months difference of PFS using a log-rank test with two-sided alpha of 0.05.

Target Accrual: Recruitment is ongoing. Up to 256 evaluable subjects will be enrolled within 24 months. (ChiCTR-IIR-17014036).

Citation Format: Yao H, Wu W, Ding L, Yu Y, Wang Y, Zeng Y, Zhao J, Li Q. FAMILY: A randomized, multicenter, open-label, phase III trial of fulvestrant versus capecitabine as maintenance therapy after first-line combination chemotherapy in patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-05-01.