Abstract OT1-04-01: Adjuvant ovarian suppression plus aromatase inhibitor or tamoxifen for hormone receptor-positive breast cancer in women younger than 35 (ASPAIT): A multicenter randomized clinical trial

In SOFT study, subgroup analysis for hormone receptor-positive (HR+) breast cancer women younger than 35 years indicated better 5-year DFS in OFS+exemestane arm than OFS+tamoxifen. Since only about 11% of women included were younger than 35 years of age, this subgroup analysis result is underpowered. In addition, there still no specific randomized clinical trial focusing on endocrine treatment in women younger than 35 years of age. The purpose of this study is to compare the efficacy of gonadotropin releasing hormone agonists (GnRHa)+tamoxifen versus GnRHa+AIs in HR+ early breast cancer patients under age 35 with intermediate or high risk for disease recurrence. Study design This is a prospective, open label, multicentre, randomized controlled trial that compared the efficacy of GnRHa+tamoxifen versus GnRHa+AIs in HR+ early breast cancer patients under age 35 with intermediate or high risk for disease recurrence. This study was initiated by the first affiliated hospital of Sun Yat-sen university in 2016. Twenty-four hospitals in China participate in this trial. The protocol was approved by the appropriate regulatory and ethics authorities for each centre. This trial has been registrated at ClinicalTrials.gov. The NCT Number is NCT02914158. Criteria for patient eligibility: 1. Written informed consent must be signed. 2. ECOG≤2. 3. Histologically proven HR+ (ER≥1% by IHC) invasive breast cancer. 4. Age≤35, premenopausal. 5. No distant metastatic disease. 6. T≥2cm or with at least 1 axillary lymph node involved. 7. Patient must accept proper surgery, systemic therapy and radiation therapy if necessary. 8. Laboratory exam criteria for enrollment: hemoglobin ≥10g/dl, white blood cell ≥4,000/mm3, platelets ≥100,000/mm3, glutamic oxalacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase ≤2 times upper limit of normal (ULN), total bilirubin, creatinine clearance rate ≤1.5 times ULN. Criteria for patient ineligibility: 1. Patients who are pregnant or lactating at the time of randomization or refuse to contraception.2. Patients who received organ transplantation. 3. Patients who have other malignant diseases within 5 years. 4. Patients with psychiatric disorder, peripheral or central nerve system disease or any disorder, which compromises ability to give informed consent or participate in this study. 5. Patients with sever hepatic, renal, cardiovascular, respiratory, digestive diseases or uncontrolled diabetes. 6. Patients who participate in other clinical trials. 7. Patients who allergy to goserelin, leuprorelin, tamoxifen or AIs. Statistical analysis According to previous results, 5-year DFS for OFS+tamoxifen in HR+ breast cancer patients under age 35 with intermediate or high risk of disease recurrence was 73% vs. 81% for OFS+AIs. This trial designed 80% power to detect a between-group difference using a two-sample log-rank test (two-sided a=0.05). To allow for missing 10% data, the study planned to enroll 680 patients (340 patients for each group) in 5 years. The statistical design assumed that 197 primary end point events should occur during 5-year follow-up and OFS+AIs should decrease 30% DFS relative risk. The calculations were performed using PASS 11. Treatment details Patients enrolled are randomized 1:1 to two arms in 8 weeeks after surgery, adjuvant chemotherapy or radiation therapy. Goserelin 3.6mg or leuprorelin 3.75mg is injected subcutaneously every 28 days for 5 years. Arm A: Tamoxifen 20mg orally daily. Arm B: Exemestane 25mg, letrozole 2.5mg or anastrozole 1mg orally daily. Stratification Stratified by HER2 and axillary lymph node status. Primary end point: Disease free survival. Secondary end point: Overall survival. Invasive Breast Cancer Recurrence-Free Interval. Adverse Effects Rate. Citation Format: Zhen Shan, Nan Shao, Zhongyu yuan, Qianjun Chen, Anqin Zhang, Kun Wang, Ailing Zhang, Li Cai, Yuhua Song, Herui Yao, Hongmin Ma, Heng Huang, Jianwen Li, Yuanqi Zhang, Lehong Zhang, Jincai Zhong, Hui Liu, Zhiyong Wu, Li Zhao, Feihai Ling, Weixiong Yang, Rui Zhuo, Xiangyang Song, Ying Lin. Adjuvant ovarian suppression plus aromatase inhibitor or tamoxifen for hormone receptor-positive breast cancer in women younger than 35 (ASPAIT): A multicenter randomized clinical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-04-01.