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Backgrounds <p>High-grade radiologic extranodal extension (G2/3-rENE) is a well-established adverse prognostic factor in nasopharyngeal carcinoma (NPC), as demonstrated in our previous research. This study aims to evaluate the efficacy and safety of combining a PD-1 inhibitor with induction chemotherapy (IC) in this high-risk patient population.</p> Methods <p>We retrospectively analyzed 217 histologically confirmed non-metastatic NPC patients from three centers. Group A (<i>n</i> = 104) received IC plus anti-PD-1 therapy followed by concurrent chemoradiotherapy (CCRT), while Group B (<i>n</i> = 113) received IC alone followed by CCRT. Clinical response rates, survival outcomes, and treatment-related toxicities were compared, and subgroup analyses were performed.</p> Results <p>Post-IC, Group A demonstrated superior clinical outcomes compared to Group B, with a significantly higher complete response rate (CRR: 21.15% vs. 7.96%, <i>p</i> = 0.001) and objective response rate (ORR: 97.12% vs. 88.50%, <i>p</i> = 0.001). Furthermore, the combination group showed markedly improved rates of 2-year progression-free survival (PFS: 93.2% vs. 81.0%) and distant metastasis-free survival (DMFS: 97.1% vs. 84.8%). Subgroup analyses revealed that patients with baseline EBV DNA &lt; 400 IU/mL, LDH &lt; 2×ULN, T3–4 or N2-3 stage, stage IVa disease, and G3-rENE benefited more from combined treatment. Post-treatment immune profiling revealed reduced total lymphocyte counts with decreased CD4⁺and increased CD8⁺T cells, resulting in a lower CD4⁺/CD8⁺ratio. Morover, patients exhibiting a less pronounced decrease in this ratio were more likely to achieve a complete response.</p> Conclusions <p>PD-1 blockade with IC significantly improves disease control in high-risk NPC patients with G2/3-rENE. T cell subset dynamics may help predict treatment response, supporting the incorporation of immunotherapy regimens as frontline treatment for this patient population.</p>

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Efficacy of PD-1 inhibitor plus induction chemotherapy for nasopharyngeal carcinoma with high-grade extranodal extension: a multicenter retrospective analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Pingting Zhou,
  • Xunmei Liu,
  • Shuang Huang,
  • Yunxiu Luo,
  • Yuefeng Hu,
  • Fapeng Wang,
  • Rensheng Wang,
  • Tingting Zhang

摘要

Backgrounds

High-grade radiologic extranodal extension (G2/3-rENE) is a well-established adverse prognostic factor in nasopharyngeal carcinoma (NPC), as demonstrated in our previous research. This study aims to evaluate the efficacy and safety of combining a PD-1 inhibitor with induction chemotherapy (IC) in this high-risk patient population.

Methods

We retrospectively analyzed 217 histologically confirmed non-metastatic NPC patients from three centers. Group A (n = 104) received IC plus anti-PD-1 therapy followed by concurrent chemoradiotherapy (CCRT), while Group B (n = 113) received IC alone followed by CCRT. Clinical response rates, survival outcomes, and treatment-related toxicities were compared, and subgroup analyses were performed.

Results

Post-IC, Group A demonstrated superior clinical outcomes compared to Group B, with a significantly higher complete response rate (CRR: 21.15% vs. 7.96%, p = 0.001) and objective response rate (ORR: 97.12% vs. 88.50%, p = 0.001). Furthermore, the combination group showed markedly improved rates of 2-year progression-free survival (PFS: 93.2% vs. 81.0%) and distant metastasis-free survival (DMFS: 97.1% vs. 84.8%). Subgroup analyses revealed that patients with baseline EBV DNA < 400 IU/mL, LDH < 2×ULN, T3–4 or N2-3 stage, stage IVa disease, and G3-rENE benefited more from combined treatment. Post-treatment immune profiling revealed reduced total lymphocyte counts with decreased CD4⁺and increased CD8⁺T cells, resulting in a lower CD4⁺/CD8⁺ratio. Morover, patients exhibiting a less pronounced decrease in this ratio were more likely to achieve a complete response.

Conclusions

PD-1 blockade with IC significantly improves disease control in high-risk NPC patients with G2/3-rENE. T cell subset dynamics may help predict treatment response, supporting the incorporation of immunotherapy regimens as frontline treatment for this patient population.