Concurrent chemoradiotherapy with or without nimotuzumab in induction chemotherapy resistant locoregionally advanced nasopharyngeal carcinoma: An open-label randomised, controlled, phase 2 trial.

6064 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is the current standard of care for locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Patients resistant to IC have a high risk of treatment failure. Nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) antibody, has shown potential efficacy in combination with CCRT. This randomized phase 2 trial aimed to evaluate the efficacy and safety of nimotuzumab plus CCRT compared to CCRT alone in IC-resistant LA-NPC. Methods: We conducted an open-label, randomized phase 2 trial at Sun Yat-sen University Cancer Center, Guangzhou, China. Eligible patients (aged 18–70) had untreated, nonkeratinizing, IC-resistant stage II–IVa (the 8 th edition of the American Joint Committee on Cancer classification system) LA-NPC, defined as detectable plasma Epstein-Barr virus (EBV) DNA and/or stable/progressive disease after two cycles of IC. Other inclusion criteria were ECOG performance status of 0–1, positive EGFR expression and adequate organ function. Patients were randomized (1:1) to receive CCRT plus nimotuzumab or CCRT alone. Cisplatin (100 mg/m²) was given on days 1, 22, and 43 of intensity-modulated radiotherapy in both groups. In the experimental group, nimotuzumab (200 mg) was administered weekly during CCRT. Randomization was done using a computer-generated code random number code with a block size of six, stratified by disease stage. The primary endpoint was 2-year progression-free survival (PFS) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of the assigned treatment. The study was registered at ClinicalTrials.gov (NCT04223024), and patients are under follow-up. Results: Two hundred forty-six patients were enrolled and randomized (121 to CCRT plus nimotuzumab, 125 to CCRT alone). At a median follow-up of 47 months (IQR 44–50), the 2-year PFS was 81.0% (95% CI 72.8–86.9) in the CCRT plus nimotuzumab group and 80.8% (95% CI 72.7–86.7) in the CCRT group (stratified HR 0.93 [95% CI 0.59–1.47], p=0.70). The most frequent grade 3–4 adverse events were mucositis (24 [20.2%] vs 22 [17.6%]), leukopenia (23 [19.3%] vs 21 [17.2%]), and nausea (14 [11.8%] vs 16 [13.8%]) in the CCRT plus nimotuzumab group compared with CCRT group. A higher frequency of grades 1–2 rash was observed in the CCRT plus nimotuzumab group (15 [12.6%] vs 6 [4.9%]). Late adverse events were predominantly mild, with no grade 4 events reported in either group. No treatment-related deaths occurred in either group. Conclusions: In IC-resistant LA-NPC, the addition of nimotuzumab to CCRT did not provide a significant survival benefit. Further research into predictive biomarkers and novel combinations is needed to optimize treatment for high-risk populations. Clinical trial information: NCT04223024 .