Efficacy and safety analysis of PD-1 inhibitors combined with chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

OBJECTIVE: This study aimed to assess the efficacy and safety of integrating programmed death-1 (PD-1) inhibitors with chemoradiotherapy (CRT) in the treatment of locally advanced nasopharyngeal carcinoma (LA-NPC), explore the optimal sequencing of immunotherapy, and to compare the short-term efficacy of different combination regimens during the induction phase. METHODS: We retrospectively analyzed 512 LA-NPC patients (stage III-IVA, excluding T3N0). Among these patients, 256 received PD-1 inhibitors combined with CRT, and another 256 underwent CRT alone. The two groups were matched for T stage, N stage, overall tumor stage, sex, and age. We compared outcomes including progression-free survival (PFS), distant metastasis-free survival (DMFS), locoregional failure-free survival (LRFFS), overall survival (OS), and adverse events between the two groups. Further subgroup analyses examined the 3-year PFS rates according to the timing of PD-1 inhibitor administration (induction, concurrent, and maintenance immunotherapy, induction plus concurrent immunotherapy, and induction-phase immunotherapy). We also compared the short-term efficacy of PD-1 inhibitors combined with induction chemotherapy (IC) versus IC alone, and the efficacy variations associated with antiangiogenic or anti- epidermal growth factor receptor (EGFR) therapy, different PD-1 inhibitors, and chemotherapy protocols. RESULTS: The PD-1 inhibitor combined with CRT group showed significantly improved 3-, 4-, and 5-year rates of PFS, OS, and DMFS compared to the CRT group (3-year PFS: 90.6% vs. 82.6%, 4-year PFS: 89.3% vs. 77.3%, 5-year PFS: 89.3% vs. 76.1%; all p < 0.05). No notable difference was observed in LRFFS. Subgroup analyses revealed no significant variation in 3-year PFS rates among different PD-1 inhibitor administration schedules. Following IC, the PD-1 inhibitor plus IC cohort demonstrated higher complete response rates and objective response rates for primary nasopharyngeal lesions, cervical lymph nodes, and retropharyngeal lymph nodes than the IC cohort. The addition of antiangiogenic or anti-EGFR therapies further improved these response rates. The incidence of adverse events was comparable between the two groups. CONCLUSIONS: Combining PD-1 inhibitors with CRT significantly improves PFS, DMFS and OS in LA-NPC patients, with a favorable safety profile. No significant differences in efficacy were found across different PD-1 inhibitors and chemotherapy regimens, suggesting flexibility in treatment selection based on clinical circumstances.