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

Rákkutatás · Nasopharyngeal carcinoma

PD-1 blockade with induction chemotherapy significantly improves disease control in high‑risk nasopharyngeal carcinoma patients with high‑grade extranodal extension (G2/3‑rENE).

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. Moreover, 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.

The study demonstrates that adding a PD‑1 inhibitor to induction chemotherapy improves complete response rates, objective response rates, and progression‑free survival in nasopharyngeal carcinoma patients with high‑grade extranodal extension, a known adverse prognostic factor. This evidence supports expanding frontline immunotherapy to this high‑risk subgroup, potentially improving outcomes and informing guideline recommendations.

Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.

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