Metronomic Capecitabine With an Aromatase Inhibitor Demonstrates Safety, Efficacy in Treatment of HR+, HER2– Metastatic Breast Cancer

Metronomic capecitabine (Xeloda; Genetech) plus an aromatase inhibitor in the first line demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC). The results are from the randomized, controlled phase 3 MECCA trial (NCT02767661).¹

Breast cancer cells | Image Credit: © Jack - stock.adobe.com

Endocrine therapy (ET) is the standard of care for patients with HR+, HER2– MBC; however, many eventually develop a resistance. Novel therapies, such as CDK4/6 inhibitors have demonstrated success in overcoming or delaying ET resistance. There remains a need for development of additional therapeutic approaches, namely combination therapies, to improve survival outcomes in these patients.²

Emerging studies show that metronomic chemotherapy may be a promising option for patients with breast cancer through improved clinical efficacy and milder toxicities compared with maximum tolerated dose chemotherapy. Metronomic CT is a method of administering low-dose chemotherapy more frequently, rather than a larger dose in 1 session. This supports growing interest in optimizing dosing regimens and is a move away from historical dose escalation approaches, which is based on the premise that higher toxicity yields greater efficacy.^2,3

Capecitabine is an oral chemotherapy agent that originally received accelerated approval by the FDA in 1998 for patients with MBC resistant to paclitaxel (Abraxane; Abraxis BioScience, LLC) and anthracycline-containing regimens. In 2001, it was granted approval in combination with docetaxel (Docefrez; Sun Pharmaceutical Industries Europe B.V.) for treatment of MBC progressing after anthracycline-containing chemotherapy.^2,4

In the MECCA trial, researchers evaluated the safety and efficacy of metronomic capecitabine in combination with an aromatase inhibitor. Their study involved 263 patients with HR+, HER2– MBC who were randomized 1:1 to receive either metronomic capecitabine plus an aromatase inhibitor or an aromatase inhibitor alone. The primary and secondary end points of the study included PFS and OS as well as objective response rate, disease control rate (defined as disease controlled for ≥24 weeks), and safety.²

At the 50.7-month median follow up, 203 PFS events occurred. The combination arm demonstrated a PFS of 20.9 months compared with 11.9 months in the aromatase inhibitor arm (hazard ratio [HR], 0.58 [95% CI, 0.43 to 0.76]). There was a median OS of 45.1 months in the aromatase inhibitor arm; however, this was not reached in the combination arm (HR, 0.58 [95% CI, 0.37 to 0.93]).³

The most common adverse events were grade 3 palmar-plantar erythrodysesthesia and peripheral neuropathy, which occurred in 15.1% of the patients receiving combination treatment. Overall, the safety profile was consistent with previous findings and the combination therapy was well-tolerated.³

REFERENCES

1. Metronomic capecitabine plus aromatase inhibitor for first line treatment in HR(+), Her2(-) metastatic breast cancer (MECCA). Updated February 16, 2024. Accessed January 14, 2025. https://www.clinicaltrials.gov/study/NCT02767661

2. Hong R, Xu F, Xia W, et al. 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. J Clin Oncol. January 2, 2025. doi:10.1200/JCO.24.0093

3. Gerlach A. Improving patient outcomes with innovative dosing and regimen optimization strategies. Pharmacy Times. December 11, 2024. Accessed January 14, 2025. https://www.pharmacytimes.com/view/improving-patient-outcomes-with-innovative-dosing-and-regimen-optimization-strategies

4. Cortazar P, Justice R, Johnson J, et al. US Food and Drug Administration approval overview in metastatic breast cancer. J Clin Oncol. March 19, 2012. doi: 10.1200/JCO.2011.39.2613