Nasopharyngeal Carcinoma (NPC)

Overview

Nasopharyngeal carcinoma (NPC) is an EBV-driven epithelial malignancy arising from the nasopharynx; in OncoTree it sits directly under HEAD_NECK. Annual global incidence is ~1/100,000 with marked elevation in Southern China and Southeast Asia (male:female ~2.5:1; typical onset age 40–60). WHO subtypes I (keratinising SCC), II (non-keratinising differentiated), and III (non-keratinising undifferentiated, most endemic) reflect EBV association and distinct genomic profiles.

Cohorts in the corpus

  • npc_nusingapore — referenced as study identifier in the raw extraction frontmatter for PMID:24952746; review does not directly analyse the cohort.

Recurrent alterations

  • EGFR overexpressed in a substantial fraction of NPC tumors; drives proliferation/metastasis/resistance via PI3K/AKT and MAPK; targetable with monoclonal antibodies (nimotuzumab, pimurutamab), EGFR-ADC becotatug vedotin (MRG003; ORR 39–55% in post-platinum/anti-PD-1 R/M NPC), and bispecific ADCs (BL-B01D1 EGFR×HER3 ORR 38%; GEN1286 EGFR×MET) PMID:24952746.
  • CD274 (PD-L1) and PDCD1 (PD-1) upregulated due to chronic EBV antigen exposure; PD-1/PD-L1 monotherapy ORR ~15–20%; compensatory upregulation of CTLA-4, LAG-3, TIM-3, and BTLA on exhausted T cells limits single-agent response PMID:24952746.
  • TP53 mutations and reduced immune infiltration are enriched in EBV-negative NPC vs EBV-positive NPC PMID:24952746.
  • CD276 (B7-H3) overexpressed; ADC YL201 achieved ORR 48.6% (median PFS 7.8 mo) in advanced NPC sub-cohort (n=70) PMID:24952746.
  • CDK4/CDK6 — dalpiciclib + camrelizumab (PD-1-refractory R/M NPC, n=34): ORR 32.4%, median DOR 10.4 mo, median PFS 6.7 mo PMID:24952746.
  • 8 NPC cases included in MSK-IMPACT head and neck cohort (Morris et al., N=151); PIK3CA mutation prompted PI3K-inhibitor trial enrollment in at least 1 NPC patient; NPC contributes to overall HNSC basket-trial enrollment rationale where 14% of 151 patients had NGS-guided therapy PMID:27442865.

Subtypes

  • EBV-positive (endemic) vs EBV-negative (non-endemic) NPC have distinct genomic and immune profiles; EBV-negative tumors show higher TP53 mutation rates and lower immune infiltration.

Therapeutic landscape

  • First-line R/M NPC: anti-PD-1 (toripalimab or penpulimab) + platinum/gemcitabine per NCCN PMID:24952746.
  • Phase III sintilimab + CCRT in locally advanced NPC (NCT03700476, n=425): EFS HR 0.59; 36-month EFS 86% vs 76% PMID:24952746.
  • Phase III tagitanlimab (anti-PD-L1) + gem/cis in R/M NPC (NCT05294172, n=358): PFS HR 0.47; ORR 81.7%; median DOR 11.7 mo PMID:24952746.
  • PD-1-refractory R/M NPC: cadonilimab (PD-1×CTLA-4) + chemo ORR 68%; apatinib + camrelizumab ORR 43.3% (ICI-refractory); becotatug vedotin ORR 30–55% PMID:24952746.
  • EBV-CTL (VANCE phase III, NCT02578641, n=330) failed to show survival benefit over chemotherapy alone in R/M EBV+ NPC PMID:24952746.

Sources

This page was processed by entity-page-writer on 2026-05-11. - PMID:27442865 — Morris et al. 2017 (JAMA Oncol). 8 NPC cases in MSK-IMPACT cohort of 151 advanced head and neck tumors; PIK3CA mutation prompted PI3K-inhibitor trial enrollment.

This page was processed by entity-page-writer on 2026-05-15.