Metronomic Capecitabine Plus Aromatase Inhibitor as Initial Therapy in Patients With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer: The Phase III MECCA Trial
Ruoxi Hong, Fei Xu, Wen Xia, Yue-E Teng, Quchang Ouyang, Qiufan Zheng, Zhongyu Yuan, Dongshao Chen, Kuikui Jiang, Ying Lin, Zhen Dai, Xinlan Liu, Qianjun Chen, Xinhong Wu, Yanxia Shi, Jiajia Huang, Xin An, Cong Xue, Xi-Wen Bi, Meiting Chen, Hui Li, Herui Yao, Guorong Zou, Heng Huang, Jingmin Zhang, Shusen Wang
Abstract
PURPOSE: The effects of metronomic chemotherapy plus endocrine therapy have yet to be elucidated through a randomized phase III clinical trial. METHODS: Randomized clinical trials were conducted at 12 centers in China from August 22, 2017, to September 24, 2021, and the final follow-up date was August 25, 2023. Patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) who had no previous systemic therapy in the metastatic setting were enrolled. Participants were 1:1 assigned to receive either metronomic capecitabine plus an aromatase inhibitor (AI) or AI alone. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), objective response rate, disease control rate (defined as disease controlled for ≥24 weeks), and safety. RESULTS: A total of 263 patients were randomly assigned, among which 254 patients formed the full analysis set. At the median follow-up time of 50.7 months, 203 PFS events occurred. The metronomic capecitabine plus AI arm exhibited a median PFS of 20.9 months compared with 11.9 months in the AI arm (hazard ratio [HR], 0.58 [95% CI, 0.43 to 0.76]). The median OS was not reached in the combination arm and was 45.1 months in the AI arm (HR, 0.58 [95% CI, 0.37 to 0.93]). The most common adverse events were palmar-plantar erythrodysesthesia and peripheral neuropathy; grade 3 events occurred in 15.1% of the patients receiving combination treatment. CONCLUSION: The MECCA trial demonstrated a significant improvement in PFS and OS with first-line metronomic capecitabine plus AI compared with AI alone in patients with hormone receptor-positive+/HER2-negative MBC. Both treatment arms exhibited tolerable safety profiles consistent with previous reports.