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

R Ruo-Xi Hong (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) F Fei Xu W Wen Xia (State Key Laboratory of Organometallic Chemistry and Shanghai Hongkong Joint Laboratory in Chemical Synthesis Key Laboratory of Synthetic and Self‐Assembly Chemistry for Organic Functional Molecules Ningbo Zhongke Creation Center of New Materials Shanghai Institute of Organic Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences 345 Lingling Road Shanghai 200032 P.R. China) Y Yue-E Teng (Department of Breast Internal Medicine, The First Hospital of China Medical University, Shenyang, China) Q Qu-Chang Ouyang (Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China) Q Qiu-Fan Zheng (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) Z Zhong-Yu Yuan (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) D Dong-Shao Chen (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) K Kui-Kui Jiang (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) Y Ying Lin (Induced Proximity Platform, Amgen Research) Z Zhen Dai (2Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China) X Xin-Lan Liu (Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, China) Q Qian-Jun Chen (State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China) X Xin-Hong Wu (Department of Breast Cancer, Hubei Cancer Hospital, Wuhan, China) Y Yan-Xia Shi (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) J Jia-Jia Huang (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) X Xin An (Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University) C Cong Xue X Xi-Wen Bi (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) M Mei-Ting Chen (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) H Hui Li H He-Rui Yao (Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China) G Guo-Rong Zou (Department of Oncology, Panyu Central Hospital, Guangzhou, China) H Heng Huang J Jing-Min Zhang (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China) S Shu-Sen Wang (Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China)

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.

Article Details

Volume / Issue Vol. 43, Issue 11
Published April 10, 2025
Pages 1314-1324
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (26)

R

Ruo-Xi Hong

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

F

Fei Xu

W

Wen Xia

State Key Laboratory of Organometallic Chemistry and Shanghai Hongkong Joint Laboratory in Chemical Synthesis Key Laboratory of Synthetic and Self‐Assembly Chemistry for Organic Functional Molecules Ningbo Zhongke Creation Center of New Materials Shanghai Institute of Organic Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences 345 Lingling Road Shanghai 200032 P.R. China

Y

Yue-E Teng

Department of Breast Internal Medicine, The First Hospital of China Medical University, Shenyang, China

Q

Qu-Chang Ouyang

Department of Breast Cancer Medical Oncology, Hunan Cancer Hospital, Changsha, China

Q

Qiu-Fan Zheng

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

Z

Zhong-Yu Yuan

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

D

Dong-Shao Chen

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

K

Kui-Kui Jiang

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

Y

Ying Lin

Induced Proximity Platform, Amgen Research

Z

Zhen Dai

2Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China

X

Xin-Lan Liu

Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, China

Q

Qian-Jun Chen

State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China

X

Xin-Hong Wu

Department of Breast Cancer, Hubei Cancer Hospital, Wuhan, China

Y

Yan-Xia Shi

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

J

Jia-Jia Huang

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

X

Xin An

Key Laboratory of Entomology and Pest Control Engineering, College of Plant Protection, Southwest University

C

Cong Xue

X

Xi-Wen Bi

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

M

Mei-Ting Chen

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

H

Hui Li

H

He-Rui Yao

Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

G

Guo-Rong Zou

Department of Oncology, Panyu Central Hospital, Guangzhou, China

H

Heng Huang

J

Jing-Min Zhang

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China

S

Shu-Sen Wang

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China