Concurrent chemoradiotherapy plus nimotuzumab versus chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma with a suboptimal response to induction chemotherapy: a randomized phase 2 trial

Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (LA-NPC); however, patients with a suboptimal response to IC, defined as detectable Epstein-Barr virus DNA and/or stable or progressive disease after IC, remain at high risk of treatment failure. Here we report an open-label, randomised, phase 2 trial evaluating whether adding nimotuzumab, a humanised anti-epidermal growth factor receptor antibody, to CCRT improves outcomes in this high-risk population. A total of 246 patients with untreated, non-keratinising, stage II-IVA LA-NPC were randomly assigned (1:1) to receive CCRT with or without nimotuzumab. The primary endpoint was 2-year progression-free survival (PFS); secondary endpoints included overall survival, distant metastasis-free survival, locoregional relapse-free survival, short-term response rate, and safety. At a median follow-up of 47 months, the 2-year PFS was 81.0% (90% confidence interval [CI], 74.3-86.1) in the nimotuzumab plus CCRT group and 80.8% (90% CI, 74.2-85.7) in the CCRT-alone group (hazard ratio, 0.93 [90% CI, 0.63-1.37]; p = 0.70). Survival outcomes were similar between groups, while low-grade rash occurred more frequently with nimotuzumab. These findings indicate that adding nimotuzumab to CCRT does not improve survival in patients with LA-NPC with a suboptimal response to IC, underscoring the need for predictive biomarkers and alternative therapeutic strategies. Trial registration: NCT04223024.