Efficacy and Safety of Adjuvant Capecitabine in Locoregionally Advanced Nasopharyngeal Carcinoma: A Meta-Analysis of Phase III Randomized Trials With Subgroup Analysis by Neoadjuvant Chemotherapy.

Abstract

Concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), yet distant metastasis remains the predominant cause of treatment failure. Two phase III randomized trials have investigated the efficacy of adjuvant capecitabine following CCRT, with or without neoadjuvant chemotherapy (NACT). We conducted a meta-analysis to evaluate the impact of adjuvant capecitabine on survival outcomes and treatment-related toxicity in LA-NPC. We included two randomized controlled trials involving 586 patients with LA-NPC who received adjuvant capecitabine or observation following definitive CCRT. Hazard ratios (HRs) for failure-free survival (FFS) and overall survival (OS) were pooled using a fixed-effects model. Subgroup analyses were performed based on NACT status. Grade ≥ 3 treatment-related adverse events were compared across treatment arms. Adjuvant capecitabine significantly improved FFS in both trials (HR = 0.51, 95% CI: 0.34-0.75; I² = 0%). A statistically significant OS benefit was also observed (HR = 0.50, 95% CI: 0.31-0.82; p = 0.005). Subgroup analysis of the Chen et al. trial revealed a consistent OS benefit in patients with and without prior NACT (HR = 0.42 and 0.48, respectively), with a pooled HR of 0.43 (95% CI: 0.27-0.71; I² = 0%). Grade ≥ 3 adverse events were more common in the capecitabine arm, particularly in the standard-dose setting (60% vs. 51% in Miao et al.; p = 0.21), but remained manageable. Adjuvant capecitabine significantly improves both failure-free and overall survival in patients with LA-NPC (stage III-IVA), regardless of prior neoadjuvant chemotherapy. Toxicity is acceptable, particularly with low-dose metronomic regimens. These findings support the incorporation of adjuvant capecitabine into standard care for high-risk LA-NPC following CCRT.