A Multicenter Randomized Controlled Trial (RCT) of Adjuvant Chemotherapy (CT) in Nasopharyngeal Carcinoma (NPC) with Residual Plasma EBV DNA (EBV DNA) Following Primary Radiotherapy (RT) or Chemoradiotherapy (CRT).

5511 Background: The benefit of adjuvant CT in NPC is unclear. Administering CT after full-dose CRT presents challenges in treatment compliance and toxicity. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Biopsy proven NPC, AJCC stage IIB-IVB, detectable EBV DNA at 6-8 wks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, adequate organ function. Randomised with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). EBV DNA and PET scan were performed before and 6 months after randomization. Primary endpoint was relapse free survival and secondary endpoints included toxicity of adjuvant CT. With a hazard ratio of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. This safety analysis was approved by DMSC. Results: From 9/2006 to 12/2011, 514 pts consented for EBV DNA screening, 95 with detectable EBV DNA consented for adjuvant study. After work-up, 74 were eligible for randomization (37 to arm A; 37 to arm B). The two arms were well balanced in baseline characteristics. 80% received prior neoadjuvant and/or concurrent CT. Staging: IIB (36.5%), III (29.7%), IVA (18.9%), IVB (14.8%). Five pts refused adjuvant CT after randomization. Overall 65% and 57% completed 5 and 6 cycles respectively. Mean dose intensity (DI): 84% for cisplatin (22.5 mg/m2/wk, range 0.0-26.7), 92% for gemcitabine (612.8 mg/m2/wk, range 333.3-777.8). Treatment related adverse events above CTC G2 were summarized in Table. Conclusions: Delivery of 6 cycles of adjuvant CT is feasible with acceptable toxicity after full dose RT or CRT. [Table: see text]