Background: Concurrent chemoradiotherapy (CCRT) is currently considered to be the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC), accompanied with non-neglectable toxicity and unsatisfactory compliance. Therefore, it is highly warranted to explore an alternative regimen for LA-NPC. This trial aimed to assess and investigate the efficacy and safety of recombinant human endostatin (Rh-endostatin) with intensity-modulated radiotherapy (IMRT) for low-risk LA-NPC. Methods: Patients with low-risk LA-NPC were randomly assigned into ERT group (n=60, receiving Rh-endostatin plus radiotherapy) and CCRT group (n=60, receiving cisplatin plus radiotherapy). The primary endpoint was the 5-year overall survival (OS). Non-inferiority was shown if the upper limit of the 95% CI for the difference in 5-year OS between the ERT group and CCRT group did not exceed 15%. The secondary endpoint was 3-year progression-free survival (PFS). Results: A total of 120 patients were included in the trial. After a median follow-up of 71 months (IQR 62-75), the 5-year OS rate was 88.1% in the ERT group and 77.6% in the CCRT group, with a difference of 10.5% (95% CI: -0.03 to 0.24; P_{non-inferiority} = 0.002). Patients in the ERT group had better 3-year PFS than that in the CCRT group (89.8% vs 70.6%; HR = 0.362; 95% CI: 0.150-0.873; P_log-rank = 0.018). The overall all-grade toxicity burdens were heavier in CCRT group. No patients died of treatment-related causes. Conclusions: Rh-endostatin combined with IMRT had favorable efficacy, fewer toxic effects and more improved quality of life, which might be a promising alternative regimen to CCRT for low-risk LA-NPC in clinic. Clinical trial information: NCT02237924.

Data are % (95% CI). OS, overall survival; PFS, progression-free survival; LRRFS, locoregional recurrence-free survival; DMFS, distance metastasis-free survival (DMFS) rate.