In a Chinese phase III study reported in The Lancet, Chen et al found that the use of adjuvant metronomic capecitabine improved failure-free survival vs observation after definitive chemoradiotherapy in patients with high-risk locoregionally advanced nasopharyngeal carcinoma.
In the open-label multicenter trial, 406 adult patients aged up to 65 years were randomly assigned between January 2017 and October 2018 to receive metronomic capecitabine at 650 mg/m² twice daily for 1 year (n = 204) or observation (standard therapy group, n = 202). Random assignment was stratified by study center and receipt vs no receipt of induction chemotherapy. Patients had to have high-risk disease (stage III–IVA, excluding T3–4N0 and T3N1 disease) with no locoregional disease or distant metastasis after definitive chemoradiotherapy, and had to have received their final radiotherapy dose 12 to 16 weeks before random assignment. The primary endpoint was failure-free survival (with disease recurrence consisting of distant metastasis or locoregional recurrence) in the intention-to-treat population.
Median follow-up was 38 months (interquartile range = 33–42 months). Failure-free survival at 3 years was 85.3% (95% confidence interval [CI] = 80.4%–90.6%) in the metronomic capecitabine group vs 75.7% (95% CI = 69.9%–81.9%) in the standard therapy group (stratified hazard ratio [HR] = 0.50, 95% CI = 0.32–0.79, P = .0023).
Rates at 3 years were 93.3% vs 88.6% for overall survival (stratified HR = 0.44, 95% CI = 0.22–0.88, P = .018); 89.4% vs 82.1% for distant failure–free survival (stratified HR = 0.52, 95% CI = 0.30–0.88, P = .014); and 92.6% vs 87.8% for locoregional failure–free survival (stratified HR = 0.50, 95% CI = 0.25–0.98, P = .0410).
Grade 1 or 2 adverse events were observed in 73% of patients in the metronomic capecitabine group vs 51% of the standard therapy group. Grade 3 adverse events occurred in 17% vs 6% of patients, with the most common in the capecitabine group being hand-foot syndrome (9%). The only grade ≥ 4 event observed was grade 4 neutropenia in one patient in the capecitabine group. The most common adverse events of any grade in the capecitabine group were hand-foot syndrome (58%) and fatigue (27%) among nonhematologic toxicities, and anemia (35%, grade 3 in < 1%) and leukopenia (27%, grade 3 in 3%) among hematologic toxicities. No serious adverse events were reported in either group. Treatment was discontinued due to adverse events in 5% of patients in the capecitabine group.
The investigators concluded, “The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma.”
Jun Ma, MD, of the Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, is the corresponding author for The Lancet article.
Disclosure: The study was supported by the National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, and others. For full disclosures of the study authors, visit thelancet.com.