PD-1 Blockade and Bevacizumab Replace Cisplatin in Locoregionally Advanced Nasopharyngeal Carcinoma

Inclusion Criteria:

1. Voluntary participation with Written informed consent.
2. Age ≥ 18 years and ≤ 65 years.
3. Histologically confirmed with Nonkeratinizing carcinoma of the nasopharynx (differentiated or undifferentiated type).
4. Original clinical staged as III-IVa (according to the 8th AJCC edition).
5. Stage III patients should meet the criteria of EBV DNA≥4000 cps/ml.
6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
7. Patients must have adequate organ function:
8. White blood cell count (WBC)≥4.0×109 /L, Hemoglobin ≥ 90g/L, Platelet count ≥100×109/L.
9. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upperlimit of normal (ULN),serum total bilirubin (TBIL) ≤2.0 times the upper limit ofnormal (ULN) .
10. Adequate renal function: creatinine clearance rate≥60 ml/min or Creatinine ≤1.5×upper limit of normal value.
11. INR, APTT≤1.5 x ULN.

Exclusion Criteria:

1. Subjects with recurrent or metastatic nasopharyngeal carcinoma.
2. Histologically or cytologically confirmed with keratinizing squamous cell carcinoma ofthe nasopharynx.
3. Prior therapy with systemic therapy for nasopharyngeal carcinoma.
4. Prior exposure to immune checkpoint inhibitors,including anti-PD-1, anti-PD-L1,anti-CTLA-4 antibodies.
5. Prior exposure to antiangiogenic agents.
6. Tumor invasion to the intracranial with clinical symptoms accompanied by cerebraledema, requiring hormone therapy.
7. Any grade ≥2 bleeding event (according to CTCAE 5.0) occurred within 4 weeks prior toenrollment.
8. Subjects with an active, known or suspected autoimmune disease.
9. Subjects with clinically significant cardiovascular and cerebrovascular diseases.
10. Subjects with high blood pressure who cannot be controlled well with antihypertensivedrugs.
11. Subjects with previous digestive tract bleeding history within 3 months or evidentgastrointestinal bleeding tendency.
12. Subjects with arterial / venous thrombosis events occurred within 6 months of thefirst dose.
13. Women in the period of pregnancy, lactation, or reproductive without effectivecontraceptive measures.
14. Seropositivity for human immunodeficiency virus (HIV).
15. Known history of other malignancies (except cured basal cell carcinoma or carcinoma insitu of the cervix).