1108OChemotherapy plus local-regional radiotherapy versus chemotherapy alone in primary metastatic nasopharyngeal carcinoma: A randomized, open-label, phase III trial

Abstract Background The role of locoregional radiotherapy in patients with primary metastatic nasopharyngeal carcinoma (mNPC) is unclear. Methods In our open-label, phase 3, multi-centre randomized controlled trial, patients with primary mNPC, staged at IVc at the diagnosis of NPC were enrolled. Key inclusion criteria were CR or PR evaluated by imaging study after three cycles of chemotherapy according to the RECST v1.1; a KPS of at least 70. Eligible patients were randomly assigned in a 1:1 ratio to receive either chemotherapy plus radiotherapy or chemotherapy alone. Chemotherapy regimens were fluorouracil at 5 g/m2 over 120 h and cisplatin at 100 mg/m2 on day 1 once every 3 weeks for a maximum of six cycles. The primary endpoint was OS. We did efficacy analyses in ITT population. Safety analyses were done in patients receiving allocated treatment. This study is registered with ClinicalTrials.gov, number NCT02111460, and is ongoing. Results Between April 2014 and August 2018, 126 eligible patients were randomly assigned to receive chemotherapy plus radiotherapy (n = 63), or chemotherapy alone (n = 63). In August 2018, the randomization was temporarily suspended due to an imbalance in deaths between the two groups and the ad hoc IDMC and the ethics committee of SYSUCC both recommended that the trial be permanently closed to new patient enrollment after IDMC confirmed the previously identified imbalance with this additional follow-up data in February 2019. The median follow-up time for OS was 25.2 months. The median OS was 40.2 months (95%CI 25.7-54.7) in the chemotherapy plus radiotherapy group and 24.5 months (95%CI 15.3-33.7) in the chemotherapy alone (HR 0.45 95% CI 0.25-0.80; P = 0.007). No significant differences between the two treatment groups were observed in terms of hematological toxicity and gastrointestinal reaction. The frequency of grade 2-3 skin reaction and grade 3-4 mucositis in chemotherapy plus radiotherapy was significantly higher than those in chemotherapy alone groups (P