Adjuvant Apatinib in Nasopharyngeal Carcinoma With Residual Epstein-Barr Virus DNA After Radiation Therapy: A Biomarker-Driven, Phase 2 Trial

Xu Liu, Ling Guo, Fang Yun Xie, Wei Han Hu, Ming Yuan Chen, Qing Mei He, Zhi Min Xu, Chu Qing Zhang, Ying Lin Peng, Ling Long Tang, Yan Ping Mao, Rui Sun, Ji Bin Li, Athanassios Argiris, Edwin P. Hui, Ying Sun, Jun Ma

Research output: Contribution to journalArticlepeer-review


Purpose: We previously demonstrated that real-time monitoring of plasma Epstein-Barr virus DNA (EBV DNA) during chemoradiation therapy defined 4 distinct phenotypic clusters of nasopharyngeal carcinoma. In particular, the treatment-resistant group, defined as detectable EBV DNA at the end of radiation therapy, had the worst prognosis and is thought to have minimal residual disease. Methods and Materials: This is the first phase 2 trial to use a targeted agent, apatinib (an inhibitor of vascular endothelial growth factor receptor 2 tyrosine kinase), in the treatment-resistant group. Eligible patients had plasma EBV DNA > 0 copies/mL at the end of radiation therapy (±1 week). Patients received apatinib (500 mg, once daily) until disease progression, unacceptable toxicity, or for a maximum of 2 years. The primary endpoint was disease-free survival (DFS). Results: Twenty-five patients were enrolled and 23 patients who received apatinib were included in the analyses. Three-year DFS was 47.8% and overall survival was 73.9%. Patients with plasma vascular endothelial growth factor–A ≤150 pg/mL at 28 days after the initiation of treatment had significantly better 3-year DFS (66.7% vs 14.3%; P =.041) and overall survival (88.9% vs 42.9%; P =.033). The most common adverse event of grade ≥3 was nasopharyngeal necrosis (26%), oral/pharyngeal pain (22%), and hand-foot syndrome (22%). Nineteen patients had serial EBV DNA data. Fourteen patients had plasma EBV DNA clearance (turn to 0), and 5 (36%) of these 14 patients had disease recurrence or death, whereas all 5 patients without EBV DNA clearance had disease recurrence or death (3-year DFS: 64.3% vs 0%; P =.001). Conclusions: The use of antiangiogenic agents shortly after radiation therapy might increase the risk of necrosis. This approach needs to be avoided until translational and preclinical studies reveal the underlying mechanism of interaction between radiation therapy and antiangiogenic agents.

Original languageEnglish (US)
Pages (from-to)1063-1071
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number5
StatePublished - Aug 1 2022

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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