Local therapy to recurrent/metastatic foci augments the benefit of immune checkpoint inhibitors in nasopharyngeal carcinoma.

BACKGROUND: The success of immunotherapy in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) necessitates a reassessment of local therapy as consolidation or salvage. This study aims to explore whether adding local therapy to immunotherapy can yield meaningful survival benefits for RM-NPC patients. PATIENTS AND METHODS: 223 patients diagnosed with RM-NPC were retrospectively included in the study. 106 received immune checkpoint inhibitor therapy (ICI) alone, and 117 received local therapy combined with ICI (LOCI). Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were further conducted to mitigate major clinically-relevant confounders. Kaplan-Meier method and Cox proportional hazards model were used to perform survival analyses and evaluate the prognostic factors. RESULTS: The median follow-up was 32.93 m (22.23-46.37 m). Patients receiving LOCI derived a significantly improved PFS when compared to the ICI group (median PFS, 30.53 m vs 16.77 m, HR, 0.524; 95%CI, 0.339-0.785; log-rank p = 0.0014). The PFS benefit remained after PSM and IPTW adjustment. In subgroup analysis, for patients with nasopharyngeal/nodal relapse (LRR-NPC), LOCI group achieved an improved PFS with a primary benefit in improving DMFS (HR, 0.437; 95%CI, 0.193-0.987; log-rank p = 0.0465) relative to the ICI group; and for patients with distant metastasis (DM-NPC), LOCI group also yielded a superior PFS (HR, 0.491; 95%CI, 0.289-0.834; log-rank p = 0.0072) than ICI group. Moreover, enhanced PFS was observed in LOCI group among patients with oligometastatic NPC (≤3 lesions) (HR, 0.458; 95%CI, 0.212-0.989; log-rank p = 0.0416). CONCLUSION: LOCI was associated with improved PFS in both recurrent and metachronous metastatic NPC patients. Strategies to select candidates for LOCI warrants further investigation.