Anti-PD-1 antibody with or without capecitabine as maintenance therapy after first-line therapy of recurrent or metastatic nasopharyngeal carcinoma.

Background: The use of maintenance therapy for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) following first-line treatment with gemcitabine, cisplatin, and anti-PD-1 antibody remains controversial. Therefore, an effective and low-toxicity maintenance treatment option is urgently needed.

Methods: This retrospective study included 301 patients who received either combined maintenance therapy (anti-PD-1 antibody plus capecitabine) or anti-PD-1 antibody alone. Patients were matched in a 1:3 ratio using propensity score matching (PSM). Progression-free survival (PFS) was the primary outcome, and its association with maintenance therapy was assessed using the log-rank test and Cox proportional hazards model.

Results: Fifty-eight patients were included in the combined maintenance therapy group. After PSM, 174 patients were included in the anti-PD-1 antibody maintenance therapy group. In the matched cohort, the 2-year PFS rate was significantly higher in the combined maintenance therapy group than in the anti-PD-1 antibody monotherapy group (66.8% vs. 51.3%, P = 0.0063). Subgroup analysis showed that patients with pre-treatment Epstein-Barr virus (EBV) DNA >12,400 copies/mL and undetectable post-treatment levels had significant improved PFS with combined maintenance therapy (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.20-0.96, P = 0.033). In contrast, no statistically significant PFS improvement from the combined maintenance therapy was observed among patients with low pre-treatment EBV DNA (≤12,400 copies/mL) and undetectable post-treatment levels (HR = 0.59, 95% CI = 0.27-1.27, P = 0.17), or those with detectable post-treatment EBV DNA levels regardless of pre-treatment levels (HR = 0.73, 95% = CI 0.31-1.70, P = 0.46). Combined maintenance therapy was associated with higher rates of grade 3-4 hand-foot syndrome (P < 0.001) and leukopenia (P = 0.0487).

Conclusion: Anti-PD-1 antibody plus capecitabine maintenance therapy improved PFS with manageable toxicities in patients with RM-MPC following first-line immunochemotherapy, particularly in those with pre-treatment EBV DNA > 12,400 copies/mL and undetectable post-treatment levels.