The results of this study show that the nimotuzumab group had significantly higher 3-year DMFS compared to the control group. Additionally, the 3-year PFS showed an increasing trend, suggesting that concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can effectively reduce distant metastasis in locally advanced NPC, and may be beneficial to PFS and OS over time.
Concurrent chemoradiotherapy following neoadjuvant chemotherapy has emerged as the standard treatment for locally advanced NPC, with the TPF regimen recommended as a grade I neoadjuvant chemotherapy[13]. Although induction chemotherapy combined with concurrent chemoradiotherapy has achieved good results in the treatment of locally advanced NPC, distant metastasis remains a major cause of treatment failure[8]. Hence, further reduction of distant metastasis and improvement of the OS rate are important and difficult issues in the treatment of locally advanced NPC.
EGFR is highly expressed in 80%-90% of patients with NPC[10]. Activation of EGFR can promote proliferation, invasion, and metastasis of tumor cells, as well as inhibit apoptosis of tumor cells, thus inducing tolerance to radiotherapy and chemotherapy[14, 15]. At present, EGFR has become a therapeutic target for NPC. Huang et al. confirmed that the addition of radiotherapy to nimotuzumab improved the overall efficacy of NPC treatment compared to radiotherapy alone[16]. Wu et al. also confirmed that radiotherapy combined with nimotuzumab can improve the efficacy of treatment for locally advanced NPC compared with radiotherapy alone[17]. In a retrospective study conducted by Lu et al., concurrent chemoradiotherapy combined with nimotuzumab was demonstrated to improve DMFS and OS compared to concurrent chemoradiotherapy in patients with NPC and cervical lymph node metastasis[18]. Sun et al. conducted a prospective, randomized, controlled, double-blind, multicenter phase III clinical trial, which demonstrated that compared with concurrent chemoradiotherapy, nimotuzumab combined with concurrent chemoradiotherapy improved the efficacy of treatment for locally advanced NPC, and the 5-year OS rate increased from 64.3–76.9% (P = 0.042)[19]. These studies collectively support the efficacy of both radiotherapy alone and concurrent chemoradiotherapy plus nimotuzumab in the treatment of locally advanced NPC. Jiang et al. reported that concurrent chemoradiotherapy combined with nimotuzumab after induction chemotherapy improved the objective remission rate and 5-year PFS compared with concurrent chemoradiotherapy alone[20]. Similarly, a retrospective study by Wang et al. confirmed that concurrent chemoradiotherapy combined with nimotuzumab after induction chemotherapy for locally advanced NPC can prolong DMFS for up to five years. For patients with N2-3, the DMFS, and OS of the nimotuzumab group were significantly prolonged[21], which was similar to the results obtained in this study. Our study further confirmed that nimotuzumab combined with concurrent chemoradiotherapy after neoadjuvant chemotherapy improved the efficacy of treatment for locally advanced NPC.Adverse reactions observed in both the nimotuzumab and control groups were comparable and oral mucosal reactions, radiation dermatitis, as well as other reactions did not increase, similar to the results of a previous study[22].
The subgroup analysis of this study revealed that patients with locally advanced NPC who were < 60 years old and had a grain/leaching ratio ≤ 4 gained a significant survival benefit when treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy combined with nimotuzumab. Patients with male,N3 disease and EGFR expression (++/+++) also showed a favorable trend in terms of survival benefits. Multivariate regression analysis identified the gran/lymph ratio as a risk factor for disease progression and distant metastasis in locally advanced NPC. The gran/lymph ratio is the ratio of absolute counts of neutrophils and lymphocytes in the peripheral blood, which may represent the balance between the pro-tumor inflammatory state and the anti-tumor immune response. Several studies have found that the gran/lymph ratio is an independent factor for tumor prognosis[23–25], confirming the results of this study. Other prognostic factors for NPC,[26–30] such as EGFR expression, EB DNA level, LDH, T stage, and N stage, were not detected in this study, which may be related to the retrospective study,relatively small sample size and short follow-up time.
This study provides clinical evidence to support the benefit of concurrent chemoradiotherapy with nimotuzumab after neoadjuvant chemotherapy for locally advanced NPC. However, this study is limited in that it is a retrospective study with a relatively short follow-up duration. Long-term follow-up to observe the 5-year survival data is required. In addition, multicenter, randomized, double-blind, large-sample prospective studies are needed to confirm these findings.