Response-adapted Modulation Therapy for Locally Advanced Nasopharyngeal Carcinoma Based on Circulating Epstein-Barr Virus DNA Level Post Induction Chemotherapy
Nasopharyngeal carcinoma is biologically different from traditional head and neck squamous cell carcinoma. The mainstay treatment for locally advanced nasopharyngeal carcinoma is cisplatin-based concurrent chemoradiation. Recent phase III randomized control trials have demonstrated that induction chemotherapy plus concurrent chemoradiation further improved progression-free survival. However, not every patient has good response to induction chemotherapy. Evidence has accumulated that those with poor response to induction chemotherapy, or those with detectable Epstein-Barr Virus (EBV) DNA post induction chemotherapy, correlated with poorer progression-free survival. Huang CL et al. (Int J Radiat Oncol Bio Phys. 2019) reported that plasma EBV DNA load at completion of induction chemotherapy was an independent and earlier predictor for progression-free survival and overall survival in locally advanced nasopharyngeal carcinoma. Lv J et al. (Nat Commun. 2019) demonstrated that real-time monitoring of plasma EBV DNA response added prognostic information, and had the potential uitility for risk-adapted treatment intensification in nasopharyngeal carcinoma. Therefore, investigators selects those with poor plasma EBV DNA response during and after induction chemotherapy, and intensifies the treatment with combination of anti-PD-1 antibody, in order to improve progression-free survival in locally advanced nasopharyngeal carcinoma, according to response-adapted strategy.
• Subjects must sign the informed consent form, and must be willing and able to comply with the visits, treatment regimen, laboratory tests and other requirements specified in the study protocol;
• Age at diagnosis: 18-70 years old;
• Firstly diagnosed, pathologically confirmed primary nasopharyngeal carcinoma with non-keratinizing carcinoma (WHO criteria);
• Locally advanced nasopharyngeal carcinoma (T3-4N0-1M0, TanyN2-3M0), staged according to the American Joint Committee on Cancer (AJCC) 8th edition clinical staging system;
• Pretreatment EBV DNA \>0;
• ECOG score: 0-1 points;
• Does not receive any treatment after the diagnosis of nasopharyngeal carcinoma;
• Normal bone marrow function: white blood cell \>4\*109/L, neutrophil count \>1.5\*109/L, hemoglobin concentration \> 90g/L, platelet count \>100\*109/L;
• Normal liver and kidney function: total bilirubin ≤1.5 times the upper limit of normal; aspartate aminotransferase and/or alanine aminotransferase ≤ 2.5 times the upper limit of normal; creatinine clearance ≥ 60mL/min;
⁃ For those with hepatitis B infection, the HBV DNA load must be \< 2500 copies/ml at the time of screening; For those with anti-hepatitis C virus antibody, HCV RNA must be negative at the time of screening;
⁃ Female subjects of childbearing potential and male subjects with partners of childbearing potential must agree to use reliable contraception (e.g. condoms, regular contraceptives as directed) from screening through 1 year after treatment.