Treatment with metronomic capecitabine plus an aromatase inhibitor (AI) demonstrated improvements in both progression-free survival (PFS) and overall survival (OS) among patients with hormone receptor (HR)—positive, HER2-negative metastatic breast cancer, according to data from the phase 3 MECCA trial which were published in the Journal of Clinical Oncology.
At a median follow-up time of 50.7 months, a total of 203 PFS events occurred. In the investigational arm, patients who received metronomic capecitabine plus an AI had a median PFS of 20.9 months compared with 11.9 months in those who received an AI alone. Furthermore, in the investigational arm, the median OS was not reached, whereas in the AI alone arm, it was 45.1 months. Regarding safety, the most common side effects to treatment were palmar-plantar erythrodysesthesia and peripheral neuropathy.
“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,” lead study author, Dr. Ruo-Xi Hong, stated in the journal.
Hong works in the Department of Medical Oncology, State Key Laboratory of Oncology in South China, as well as the Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, in Guangzhou, China.
Glossary:
Progression-free survival (PFS): the amount of time a patient lives without their cancer growing or spreading, after starting treatment.
Overall survival (OS): the average amount of time a patient lives after being diagnosed with or starting treatment for a disease.
Palmar-plantar erythrodysesthesia: a skin reaction that affects the palms of the hands and soles of the feet.
Peripheral neuropathy: a condition that occurs when the peripheral nervous system is damaged.
Objective response rate (ORR): the percentage of patients who have a complete or partial response to a treatment.
Disease control rate (DCR): the percentage of patients who have a complete response, partial response, or stable disease to a treatment.
According to the journal publication, most patients with metastatic breast cancer have HR-positive disease, making endocrine therapy the standard initial treatment; however, resistance to this therapy necessitates treatment with additional therapies. Therefore, the MECCA phase 3 trial investigators therefore sought to investigate whether metronomic capecitabine combined with endocrine therapy can improve outcomes for patients with HER-positive, HER2-negative metastatic breast cancer.
More Information on the MECCA Trial
The MECCA trial was a randomized, open-label, phase 3 study comparing metronomic capecitabine plus an AU versus AI alone in patients with HR–positive, HER2-negative metastatic breast cancer who had not received prior systemic treatment in the metastatic setting. The investigation was conducted across 12 centers in China and enrolled eligible patients aged between 18 and 70 years who presented with measurable or bone-only disease and adequate organ function. Patients with primary endocrine therapy resistance, symptomatic visceral metastases posing immediate risks or uncontrolled central nervous system involvement were excluded from the trial.
Participants were randomly assigned to receive either treatment with capecitabine at 500 milligrams (mg) three times a day plus AI or AI alone, stratified by disease site and endocrine therapy sensitivity. Treatment continued until disease progression, unacceptable toxicity or patient withdrawal, and dose modifications were permitted for capecitabine but not for AI; patients could discontinue one treatment while continuing the other.
Regarding the primary end point of the study, investigators were evaluating PFS. Key secondary end points included OS, objective response rate (ORR), disease control rate (DCR), safety and tolerability. Moreover, additional secondary end points which have not yet been reported on in this analysis included patient-reported outcomes and investigational biomarker assessment.
Additional Survival and Safety Findings
The MECCA trial enrolled 263 patients across 12 centers in China between Aug. 22, 2017, and Sept. 24, 2021. In total, 254 patients (median age, 51 years; range, 30 to 74) initiated treatment, with 126 receiving capecitabine plus an AI compared with 128 receiving an AI alone. Baseline characteristics were balanced, with approximately 49% (124 patients) having visceral disease and 15.7% (40 patients) having bone-only disease. Endocrine therapy sensitivity was observed in 155 patients, while 99 had secondary endocrine therapy resistance.
Furthermore, the three- and five-year OS rates were 79% and 52% in the capecitabine plus AI group, respectively, compared with 63% and 28% in the AI group. The ORR was 37.3% in the capecitabine plus AI group and 25.0% in the AI group. Measurable disease responses were 46.1% and 28.7% and the DCRs were 88.1% and 75.8%, among these groups.
At the data cutoff, 24 of 126 patients in the capecitabine plus AI group and 13 of 128 patients in the AI group remained on treatment. Treatment duration of 24 months or more was achieved in 46 patients (36.5%) receiving capecitabine plus AI compared with 30 patients (23.4%) in the AI group.
Furthermore, dose reductions of capecitabine due to side effects occurred in 11.1% of patients, and 10.3% required temporary treatment interruption. Regarding the primary reason for treatment discontinuation, disease progression affected 64.3% of patients in the capecitabine plus AI group and 84.4% in the AI group. Treatment discontinuation due to side effects occured in 16.7% of patients in the capecitabine plus AI group and 5.5% in the AI group.
“The most common [side effect], palmar-plantar erythrodysesthesia syndrome, occurred exclusively in the capecitabine plus AI group [29.4%], with 11.1% experiencing grade 3 severity. Other [side effects] more frequent in the capecitabine plus AI group included peripheral sensory neuropathy [8.7% versus 1.6%], elevated AST [7.9% versus 4.7%], neutropenia [4.0% versus 0%], oral mucositis [2.4% versus 0%], and nausea [1.6% versus 0%, most of which were grade 1 or 2 in severity,” Hong and study authors wrote.
Reference:
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
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