What are the options for targeted therapy and immunotherapy in nasopharyngeal cancer?

Targeted Therapy and Immunotherapy Options for Nasopharyngeal Cancer

Immunotherapy combined with chemotherapy (cisplatin and gemcitabine) followed by maintenance immunotherapy should be considered the first-line treatment for recurrent and/or metastatic nasopharyngeal carcinoma (NPC), as recent phase III trials have demonstrated improved progression-free survival with this approach. 1

Immunotherapy Options

First-line Treatment for Recurrent/Metastatic NPC

• PD-1/PD-L1 Inhibitors + Chemotherapy:
  • Camrelizumab or toripalimab plus cisplatin and gemcitabine, followed by maintenance immunotherapy 1
  • Demonstrated significant improvement in progression-free survival in phase III trials
  • Pending long-term overall survival results

Monotherapy for Recurrent/Metastatic NPC

• PD-1 Inhibitors:
  • Nivolumab: 20% objective response rate (ORR)
  • Pembrolizumab: 25% ORR
  • Camrelizumab: 34% ORR
  • Most responses occur at first radiological evaluation 1

Adoptive Immunotherapy

• Cytotoxic T-cell lymphocyte (CTL) adoptive immunotherapy has shown activity in highly pre-treated patients 1
• EBV-specific approaches are particularly promising due to the causal role of EBV in NPC 1

Targeted Therapy Options

EGFR Inhibitors

• Cetuximab: Can be used as a single agent or in combination for second-line treatment 1
• Most effective for complete response among molecular targeted therapies 2

Anti-angiogenic Agents

• Bevacizumab: Most effective for partial response among molecular targeted therapies 2

Other Targeted Options

• Nimotuzumab: Most effective for overall survival and progression-free survival among targeted therapies 2

Treatment Algorithm for Recurrent/Metastatic NPC

1. First-line Treatment:

   • Cisplatin + gemcitabine + immunotherapy (camrelizumab or toripalimab) followed by maintenance immunotherapy 1
   • For patients with adequate performance status

2. Second-line Treatment (no standard exists):

   • Single agents or selected combinations of:
     • Taxanes (paclitaxel, docetaxel)
     • Fluoropyrimidines (5-FU, capecitabine)
     • Irinotecan, vinorelbine, ifosfamide, doxorubicin, oxaliplatin
     • Cetuximab 1
   • Poly-chemotherapy is more active than monotherapy (ORR 64% vs 24%) but with increased toxicity
   • PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab) as monotherapy

Special Considerations

Oligometastatic Disease

• Aggressive treatment including chemotherapy, surgery, or definitive radiotherapy to metastases may achieve long-term survival 1

Biomarkers and Monitoring

• Pre-treatment plasma EBV DNA and clearance rates are important prognostic factors in metastatic patients treated with first-line chemotherapy 1, 3
• A threshold of 2300 copies/ml has been identified as optimal predictive threshold for survival outcomes 3
• Negative post-treatment EBV DNA is associated with better prognosis 3

Emerging Approaches

• Carbon-ion radiation therapy combined with immunotherapy (camrelizumab) is being investigated for locoregionally recurrent NPC 4
• Preliminary results have shown activity and limited toxicity with proton and carbon ion therapy for locally recurrent NPC 1

Pitfalls and Caveats

• No phase III trials for immunotherapy in NPC were published prior to the recent camrelizumab/toripalimab studies
• Treatment choice should be based on previous treatments, patient symptoms, performance status, expected toxicity, and patient preference 1
• Laboratory variability exists in EBV DNA measurement methods, which should be considered when interpreting results 3
• Higher risk of bleeding has been observed with molecular targeted therapies compared to conventional treatments 2