Optimal maintenance therapy strategy for metastatic nasopharyngeal carcinoma: Insights from a cohort study in an endemic region.

6041 Background: Managing metastatic nasopharyngeal carcinoma (mNPC) remains challenging due to its high incidence and mortality rates. While maintenance therapy shows promising potential, the optimal strategy remains unclear. A prior ranking question is if combined therapy of anti-PD-1 antibodies and capecitabine an effective maintenance strategy for mNPC patients who achieved disease control after first-line therapy. Methods: Eligible patients with mNPC who achieved disease control following first-line therapy and subsequently received maintenance therapy were included at Sun Yat-sen University Cancer Center between 2018 to 2023. Progression-free survival and overall survival were analyzed using the Kaplan–Meier method and log-rank test. Cox proportional hazards model and inverse probability of treatment weighting analysis were applied to adjust for confounders. Based on interaction effects, stratification analysis was performed. A sensitivity analysis was based on the E-value from the weighted Cox proportional hazards model. Results: This cohort study included 300 mNPC patients receiving maintenance therapy with monotherapy (n=211), anti-PD-1 immunotherapy (n=94) or capecitabine (n=117), and their combination (n=89). 234 patients (78.0%) were male, and the median age was 45 years (interquartile range [IQR]: 36–54). At median follow-up of 37.8 months (IQR: 35.6–40.1), combination maintenance significantly improved progression-free survival (PFS) compared to single-drug maintenance [median PFS: not reached vs 27.0 months; weighted hazard ratio (HR): 0.569, 95% Confidence Interval (CI): 0.368-0.878, P = 0.011; E-value, 2.32], though no improvement in overall survival was observed. Stratification analysis revealed enhanced efficacy of combination maintenance in patients without prior local treatment (HR: 0.411, 95% CI: 0.266–0.748, P = 0.004) or with elevated pre-maintenance Epstein-Barr virus (EBV) DNA levels (HR: 0.312, 95% CI: 0.106–0.917, P = 0.034). No significant difference in prognosis was observed between capecitabine and anti-PD-1 monotherapy groups. Combination regimen obtained significantly superior progression-free survival compared to either monotherapy alone. The safety profile was similar between combination maintenance and single-drug groups. Conclusions: Combined anti-PD-1 and capecitabine maintenance therapy significantly improved prognosis in mNPC with disease control after first-line therapy, particularly in patients with elevated premaintenance EBV DNA levels or those without local treatment.