Long-term outcomes of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma: a randomized, controlled, multicenter, phase 3 study.

Here we report long-term outcomes of adjuvant metronomic capecitabine in patients with locoregionally advanced nasopharyngeal carcinoma. In this multicenter, open-label, parallel-group, randomized, controlled, phase 3 trial, 406 patients who had completed definitive chemoradiotherapy were randomly assigned (1:1) to receive either adjuvant metronomic capecitabine (650 mg m-2 twice daily for 1 year) or observation. The primary endpoint was failure-free survival; secondary endpoints included overall survival (OS), distant failure-free survival, locoregional failure-free survival, and safety, as reported in this analysis. The trial met its primary endpoint. With a median follow-up of 71.3 months, metronomic capecitabine significantly improved OS (hazard ratio = 0.53, 95% confidence interval, 0.31-0.91, P = 0.019). Grade 3 adverse events occurred in 35 (17%) of 201 patients in the metronomic capecitabine group and 11 (6%) of 200 in the observation group; one (<1%) grade 4 neutropenia was reported. In a post hoc analysis, completion of the 1 year course was associated with improved OS, whereas dose reductions and relative dose intensity showed no association with OS. Patients with a higher post-radiotherapy neutrophil-to-lymphocyte ratio derived greater benefit from metronomic capecitabine. These findings support the long-term therapeutic benefit of adjuvant metronomic capecitabine in locoregionally advanced nasopharyngeal carcinoma. ClinicalTrials.gov identifier: NCT02958111 .