Metronomic Therapy Shows Promise in Breast Cancer

TOPLINE:

Metronomic capecitabine combined with an aromatase inhibitor extends median progression-free survival to 20.9 months compared with 11.9 months for aromatase inhibitor alone in hormone receptor–positive breast cancer. The combination therapy demonstrates improved overall survival with tolerable safety profile, showing grade 3 adverse events in 15.1% of patients.

METHODOLOGY:

• A randomized, controlled, open-label, phase 3 trial enrolled 263 patients from 12 centers in China between August 2017 and September 2021, with final follow-up in August 2023.
• Participants with hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer without previous systemic therapy were randomly assigned 1:1 to receive either metronomic capecitabine (500 mg three times daily) plus aromatase inhibitor or aromatase inhibitor alone.
• Primary endpoint was progression-free survival, whereas secondary endpoints included overall survival, objective response rate, and disease control rate defined as disease controlled for ≥ 24 weeks.
• Analysis included 254 patients in the full analysis set, with a median follow-up time of 50.7 months.

TAKEAWAY:

• The combination therapy group achieved a median progression-free survival of 20.9 months vs 11.9 months in the aromatase inhibitor group (hazard ratio [HR], 0.58; 95% CI, 0.43-0.76; P = .0001).
• Overall survival showed significant improvement with combination therapy group with median not reached compared with 45.1 months in the aromatase inhibitor group (HR, 0.58; 95% CI, 0.37-0.93; P = .022).
• Objective response rate was higher in the combination therapy group at 37.3% vs 25.0% in the aromatase inhibitor group (odds ratio [OR], 1.79; 95% CI, 1.04-3.08; P = .0349).
• Disease control rate reached 88.1% in the combination therapy group compared with 75.8% in the aromatase inhibitor group (OR, 2.36; 95% CI, 1.20-4.64; P = .0118).

IN PRACTICE:

“We propose that the metronomic chemo-ET combination could be a first-line option for patients who cannot tolerate CDK4/6 inhibitors or in resource-constrained settings due to the economic benefits of metronomic capecitabine. The efficacy of this combination after a CDK4/6 inhibitor treatment remains unknown and warrants further investigation,” the authors of the study wrote.

SOURCE:

This study was led by Ruo-Xi Hong, MD, Sun Yat-sen University Cancer Center in Guangzhou, China. It was published online on January 2 in Journal of Clinical Oncology.

LIMITATIONS:

According to the authors, this study was initiated before cyclin-dependent kinase 4/6 inhibitor approval in China, resulting in a control group that may not represent current optimal therapy. Additionally, the impact of metronomic capecitabine plus aromatase inhibitor in patients with ESR1, PIK3CA, or AKT alterations remains unclear, pending ongoing biomarker analysis.

DISCLOSURES:

This study received support from the Sun Yat-sen University Clinical Research Program, Guangdong Basic and Applied Basic Research Foundation, Natural Science Foundation of Guangdong Province, and National Natural Science Foundation of China. Shu-Sen Wang, one of the study authors, reported receiving consulting fees from Daiichi Sankyo and AstraZeneca, speaker fees from Pfizer, Roche, AstraZeneca, Novartis, and Lilly, and research funding from Pfizer and AstraZeneca.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.