Objective: Neoadjuvant chemotherapy regimens have shown encouraging efficacy characterized by high objective response rate (ORR), pathologic complete response (pCR) rate, and major pathologic response (MPR) rate, alongside acceptable safety. This single-center retrospective study aimed to evaluate the safety and efficacy of neoadjuvant pembrolizumab plus chemotherapy in patients with locally advanced resectable oral and oropharyngeal squamous cell carcinomas (LA-OSCC/OPSCC). Materials and methods: A total of 50 patients were included. The patients received 2-4 cycles of neoadjuvant therapy with pembrolizumab, albumin-bound paclitaxel and cisplatin before surgery, followed by adjuvant radiotherapy or immunotherapy. Results: The median follow-up time was 31.7 months (95%CI, 29.4-34.0). The ORR was 85.4%, and the MPR rate was 65.8%. The 1-year event-free survival (EFS) rate was 88.8% (95%CI, 79.8%-98.8%). Patients with moderate programmed cell death ligand 1 (PD-L1) expression (combined positive score (CPS) 1 to <10) achieved the highest MPR rate (71.4%), underscoring the potential predictive value of PD-L1 expression. Treatment-related adverse events (TRAEs), most commonly alopecia, anemia, neutropenia, and nausea, were manageable. No treatment-related deaths occurred. Conclusion: This retrospective analysis indicates that neoadjuvant pembrolizumab combined with chemotherapy is a promising strategy for patients with LA-OSCC/OPSCC. Future prospective studies with larger cohorts and longer follow-up are warranted to confirm these findings.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is characterised by hyperactivation of the cyclin-dependent kinase 4/6 (CDK4/6) pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-programmed death-1 (PD-1) agents has emerged as a pivotal challenge. This prospective, single arm, phase II study (NCT05721443) evaluated the efficacy and safety of dalpiciclib, a CDK4/6 inhibitor, combined with cetuximab in patients with anti-PD-1-resistant, HPV-negative recurrent and/or metastatic HNSCC. Patients diagnosed with p16-negative R/M HNSCC resistant to first-line anti-PD-1 therapy without prior cetuximab treatment were enroled. Patients received oral dalpiciclib (150 mg daily on days 1-21 of each 28-day cycle) and intravenous cetuximab (400 mg/m2 on day 1 of cycle 1, followed by 250 mg/m2 weekly in each cycle). The primary endpoint was objective response rate (ORR), secondary endpoints were overall survival, progression-free survival, duration of response, and safety. Between March 2023 and November 2024, a total of 28 patients were enroled. The ORR was 67.9

INTRODUCTION:Oral mucosal melanoma (OMM) is a rare subtype of melanoma but exhibits highly invasive biological behavior. Programmed cell death protein 1 (PD-1) monotherapy showed lower response in OMM than other subtypes of melanoma. MATERIALS AND METHODS:We retrospectively analyzed the efficacy and safety of pembrolizumab with anlotinib in patients with advanced OMM between August 2018 and September 2024. The primary endpoint was objective response rate (ORR); the secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). RESULTS:Forty-one patients were enrolled in our study. Seventeen patients (41.4%) achieved an objective response. The median PFS was 6.4 months (95% confidence interval [CI], 4.5-8.3 months), and the median OS was 10.0 months (95% CI, 8.3-11.7 months). Thirty-three patients (80.5%) experienced at least one TRAE. The most common TRAEs were hypertension (29.3%), hand-foot syndrome (19.5%), and anemia (19.5%). Grade 3 or higher TRAEs occurred in two patients (4.8%), and no grade 5 TRAEs were observed. CONCLUSIONS:Our study suggested that pembrolizumab with anlotinib in patients with advanced OMM showed potential efficacy and manageable adverse effects. Further studies are needed to confirm the efficacy of this combination strategy.

The efficacy of immunotherapy in unresectable/recurrent/metastatic head and neck squamous cell carcinoma (U/R/M HNSCC) remains suboptimal compared to primary untreated resectable HNSCC. The immunological and stromal landscape during immunotherapy in U/R/M HNSCC is crucial for understanding drug resistance mechanisms. In this study, single-cell RNA sequencing was performed on 42 samples pre- and post-treatment from patients in our prospective trial (NCT05156970) who received immunochemotherapy. A subset of myofibroblasts expressing CD266 was identified in hampering the response to immunochemotherapy in patients with U/R/M HNSCC. This distinct subtype of cancer-associated fibroblasts (CAFs) enhanced extracellular matrix (ECM) stiffness and cellular tension through a Piezo1-mediated biomechanical mechanism, spatially segregated CD8+ T cell infiltration to establish immune-excluded niches, and ultimately facilitated immune evasion. Mechanistically, PIEZO1 inhibition suppressed YAP activation and reduced FAK phosphorylation, thereby mitigating matrix remodeling effects driven by myCAF CD266. We also observed that Piezo1 inhibition had synergistic effect with PD-1 blockade in HNSCC in vivo. In summary, our findings reveal an immunosuppressive mechanism in which stromal cells regulate ECM stiffness, presenting a potential therapeutic target for U/R/M HNSCC.

Immunotherapy has revolutionized the treatment of malignant tumors and is now recognized as a first-line option for various cancers. In resectable locally advanced oral squamous cell carcinoma (OSCC), neoadjuvant immunotherapy has been integrated into clinical practice, representing significant progress. While neoadjuvant immunochemotherapy shows promising efficacy in this setting, several critical challenges remain unresolved. These include defining optimal endpoints and response evaluation methods, identifying and managing hyperprogression, determining surgical strategies for patients with significant tumor reduction, assessing the feasibility of de-escalating postoperative adjuvant therapy in those achieving pathological complete response, and managing immune-related adverse events. This consensus addresses these challenges by integrating current evidence with pressing clinical questions and incorporating multidisciplinary expert insights from the OSCC field. The objective is to establish a standardized, unified framework for evaluating and managing these complex issues in resectable locally advanced OSCC.

Mucosal melanoma (MM), an aggressive melanoma subtype arising in mucosal tissues, displays resistance to therapies effective in cutaneous melanoma. To understand how mucosal microenvironment contributes to treatment nonresponsiveness, we performed integrative analysis of single-cell and bulk messenger RNA sequencing data derived from oral mucosa-originated melanoma and revealed that mucosa-specific inflammation induces enrichment of low-pigmented neural crest-like cancer cell, mediated by COX2+ macrophages and their secretome. Maintenance of this inflammation-induced neural crest-like state in cancer cells depends on HER2 and HER3 activation. Inhibition of HER2/3 by pan-HER inhibitors blocks cell state plasticity and overcomes chemoresistance in primary MM cell lines and patient-derived xenograft (PDX) models. These findings provide insights into how the tissue of origin determines cancer aggressiveness, highlight the role of mucosal inflammation in driving melanoma stemness and chemoresistance, and advance the identification of effective treatment options currently lacking for patients with MM.

e18098 Background: Locally advanced squamous cell carcinoma of the head and neck (HNSCC) is associated with high risks of local recurrence and distant metastasis, resulting in poor prognosis. Neoadjuvant immunochemotherapy (NICT) has emerged as a promising strategy to improve outcomes. This study aimed to explore the safety and efficacy of penpulimab (PD-1 blockade) plus chemotherapy as neoadjuvant treatment for patients with HNSCC. Methods: This phase II trial enrolled patients with untreated, locoregionally advanced, resectable HNSCC (Stage III/IVa). Patients received three cycles of NICT consisting of penpulimab (200 mg), nab-paclitaxel (260 mg/m²), and cisplatin (75 mg/m²) on day 1 of each 21-day cycle, followed by surgery. The primary endpoint was the major pathological response rate (MPR). Postoperative patients achieving MPR were randomized 1:1 to receive either alternative adjuvant treatment (Penpulimab for low-to-intermediate recurrence risk, radiotherapy + Penpulimab for high recurrence risk) or standard treatment. Those not achieving MPR received standard treatment. Secondary endpoints included 2-year DFS, ORR, local & distant MFS, OS, pCR, and safety. Results: As of January 15, 2025, 63 patients who met the inclusion and exclusion criteria were enrolled, with a median age of 59 years, 79.4% male, 92.1% with an ECOG score of 0, 92.1% with oral cancer, and 46.0% and 54.0% in Stage III and IVa, respectively. A total of 59 patients completed neoadjuvant treatment, achieving an ORR of 86.4% and a DCR of 98.3%. Among them, 50 patients underwent surgery, all achieving R0 resection. Pathological evaluations revealed that 33 patients (66.0%) met the MPR criteria. In terms of safety, 88.9% of patients experienced all-grade treatment-related adverse events (TEAEs), with 27.0% reporting ≥Grade 3 TEAEs, mainly leukopenia (4.8%) and bone marrow suppression (4.8%). Immune-related adverse events (irAEs) occurred in 38.1% of patients, with 6.3% experiencing ≥Grade 3 irAEs. Conclusions: Neoadjuvant penpulimab combined with chemotherapy demonstrated high ORR and MPR rates, with an acceptable safety profile in resectable HNSCC. These results support further investigation of this regimen in larger, randomized trials. Clinical trial information: NCT06081673 .

e18005 Background: Targeting vascular endothelial growth factor receptor (VEGFR) may synergistically enhance the antitumor effects of immune checkpoint inhibitors (ICIs). This study evaluated the efficacy and safety of camrelizumab with chemotherapy (Arm A) or apatinib (Arm B) as first-line treatment in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Methods: This open-label, double-cohort, multicenter, phase II study (NCT05156970) enrolled patients with recurrent or metastatic HNSCC who had not received prior systemic therapy for metastatic or recurrent disease. In Arm A, patients received camrelizumab (200 mg intravenous, day 1), followed by docetaxel (75 mg/m²) and cisplatin (75 mg/m²) or carboplatin (area under the curve 5) on day 2 every 3 weeks for up to six cycles, followed by camrelizumab monotherapy (200 mg intravenous, day 1, every 3 weeks). In Arm B, patients received camrelizumab (200 mg intravenous, day 1, every 3 weeks) plus oral apatinib (250 mg daily). The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), and safety. Results: Between July 2021 and May 2024, 81 patients were enrolled (41 in Arm A and 40 in Arm B). The median follow-up was 11.93 months. The median OS was 16.40 months (95% confidence interval [CI], 4.13-28.67) in Arm A and 21.00 months (95% CI, 16.63-25.37) in Arm B. The median PFS was 4.57 months (95% CI, 1.11-8.03) in Arm A and 4.20 months (95% CI, 0.00-8.54) in Arm B. The ORR was 46.3% (95% CI, 32.0%-61.0%) in Arm A and 50.0% (95% CI, 35.0%-65.0%) in Arm B. Grade 3 or higher treatment-related adverse events occurred in six patients (14.6%) in Arm A and seven (17.5%) in Arm B. Conclusions: Camrelizumab combined with chemotherapy or apatinib demonstrated encouraging survival outcomes, with a favorable safety profile. These findings support further investigation of camrelizumab-based regimens as first-line treatments for patients with recurrent or metastatic HNSCC. Clinical trial information: NCT05156970 .

Cryoablation therapy for tumors has a long history of clinical application. Its anti-tumor mechanisms and histopathological changes have been well established, with extensive clinical practice demonstrating its safety and efficacy, theoretically making it an ideal modality for tumor treatment. Historically constrained by limitations in cryogenic media and freezing equipment, its therapeutic effectiveness and clinical adoption were significantly restricted. The emergence of new-generation cryoablation systems represented by Argon-Helium cryosurgical systems has achieved substantial advancements in refrigeration efficiency, ablation range precision, and temperature monitoring accuracy, thereby greatly promoting the widespread adoption of tumor cryoablation technology. This consensus systematically summarizes the mechanisms of cryoablation technology, indications for cryotherapy in head and neck mucosal melanoma, standardized clinical treatment protocols, management of adverse reactions, and related principles. It aims to provide authoritative references for standardizing cryoablation therapy in the treatment of head and neck mucosal melanoma.

OBJECTIVE:Betel-chewing-related oral squamous cell carcinoma (BCR-OSCC) has become a global health issue with increasing incidence year by year around the world. Active prevention of the occurrence of BCR-OSCC, monitoring the population exposed to Betel Nuts, and early diagnosis and treatment are very important to maintain and improve the quality of life of patients. However, there is currently no consensus or guideline that provides targeted guidance on the management of BCR-OSCC. SUBJECTS AND METHODS:A consensus panel consisting of 15 leading Chinese experts from multidisciplinary fields was convened, and a roundtable meeting was held to discuss the topics of BCR-OSCC. RESULTS:Based on existing research reports and the experts' clinical experiences, a consensus on staging, diagnosis, and treatment for BCR-OSCC was formed through extensive discussion. CONCLUSION:This manuscript presents consensus recommendations and a summary of evidence supporting each recommendation. This consensus may improve clinical practices about BCR-OSCC in China and propel more clinical trials to provide high-level evidence for BCR-OSCC management.

6026 Background: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is characterized by hyperactivation of the cyclin-dependent kinase 4/6 (CDK4/6) pathway. As immunotherapy has become the first-line treatment for HNSCC, resistance to anti-programmed death-1 (PD-1) agents has emerged as a pivotal challenge. This phase II study evaluated the efficacy and safety of dalpiciclib, a CDK4/6 inhibitor, combined with cetuximab in patients with anti-PD-1-resistant, HPV-negative recurrent or metastatic (R/M) HNSCC. Methods: Patients diagnosed with p16-negative R/M HNSCC resistant to first-line anti-PD-1 therapy and cetuximab-naïve were enrolled. Patients received oral dalpiciclib 150 mg daily for 21 consecutive days and intravenous cetuximab (400 mg/m² on day 1 of cycle 1, followed by 250 mg/m² weekly) in 28-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS). Simon's two-stage design was used, with study termination planned if ≤1 response was observed among the first 14 patients. If met, an additional 12 patients were enrolled. Results: A total of 28 patients were enrolled, with a median age of 58 years (range 30-75 years). Among 28 evaluable patients, 3 had disease progression, 6 had stable disease, and 19 achieved partial response. The ORR was 67.9% (95% confidence interval [CI], 49.0%-82.0%), and the disease control rate was 89.3% (95% CI, 72.0%-97.0%). As of December 31, 2024, 9 patients remained on treatment. With a median follow-up of 7.34 months, the median PFS was 5.3 months (95% CI, 1.33-9.27), and the median OS was 17.0 months. Treatment-related adverse events (TRAEs) occurred in all patients, predominantly grade 1-2. The most common TRAEs were neutrophil count decreased (25/28, 89.3%), white blood cell count decreased (25/28, 89.3%), and acneiform rash (16/28, 57.1%). Grade 3 TRAEs included neutrophil count decreased (9/28, 32.1%) and white blood cell count decreased (9/28, 32.1%). No grade 4/5 TRAEs were observed. Conclusions: Dalpiciclib combined with cetuximab was well-tolerated and demonstrated potentially favorable efficacy in patients with anti-PD-1-resistant, HPV-negative R/M HNSCC. Clinical trial information: NCT05721443 .

PURPOSE:To identify the specific intratumoral and microenvironmental heterogeneity of acral melanoma (AM) and mucosal melanoma (MM), we aimed to delineate their distinct cellular compositions, evolutionary trajectories, and subtype-specific therapeutic strategies. EXPERIMENTAL DESIGN:Single-cell transcriptomic and genomic landscapes were analyzed across 42 melanoma (28 AM, 11 MM, and 3 nonacral cutaneous melanoma) samples, supplemented by in vitro and in vivo validation. Tumor and stromal cells were profiled using single-cell RNA sequencing, whole-exome sequencing, and functional assays, including transwell migration, co-culture systems, and xenograft models. RESULTS:Tumor cells exhibited divergent evolutionary routes, with MM dominated by MGP+/PCOLCE+ subpopulations showing high epithelial-to-mesenchymal transition potential. MM displayed elevated neutrophil infiltration and CXCL3+ tumor-associated macrophages, whereas AM was enriched with PI16+ cancer-associated fibroblasts promoting tumor proliferation. Molecular classification revealed MM subtypes: an antigen-presenting subtype linked to favorable outcomes and a proliferative subtype associated with recurrence. TIGIT+ regulatory T cells were enriched in AM, suggesting targeted inhibition potential. Genomic analysis connected BRAF/NRAS mutations to ALDOA+ stem-like tumor cells and identified prostaglandin D2 synthetase as a therapeutic target in triple-wild-type/melanomas. CONCLUSIONS:Our study provides a comprehensive comparison of AM and MM, uncovering subtype-specific stromal-immune interactions and molecular programs. The findings highlight actionable targets (e.g., TIGIT in AM and CXCL3+ macrophages in MM) and propose a framework for precision therapies, biomarker-driven trials, and risk stratification to improve outcomes in these aggressive melanomas.

Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.

The intricate interplay between the gut microbiome and the host immune system has been recognized as a pivotal determinant of clinical outcomes in cancer immunotherapy. Mounting evidence suggests that specific microbial communities are associated with both the efficacy and toxicity of immune checkpoint inhibitors in diverse malignancies, underscoring the microbiome’s role in modulating systemic and tumour-localized immunity. Mechanistically, the microbiome shapes antitumour immunity by affecting antigen presentation, activation of effector cells, immunosuppression and adverse effects. Key microbial components and metabolites present in distinct anatomical niches have been identified as promoters or inhibitors of therapeutic responsiveness via multiple pathways. Harnessing this knowledge, microbiome-targeted strategies such as antibiotic, probiotic, fecal microbiota transplantation, and dietary modulation are regarded as potential adjuvant therapies to enhance the efficacy of anti-tumour therapies. Although significant progress has been achieved in preclinical studies, challenges persist in translating these findings into standardized clinical applications.

Background Immune checkpoint blockade therapy has shown limited efficacy in head and neck squamous cell carcinoma (HNSCC). Sialic acid binding immunoglobulin-like lectin (Siglec)-15 has been identified as a novel immune evasion biomarker, while the role of Siglec-10 in the specific immune suppressive tumor microenvironment remains largely unknown.Methods Immunohistochemical assays were employed to investigate the correlation of the expressions of Siglec-10 and Siglec-15 with the clinicopathological features as well as the prognosis of immunotherapy in patients with HNSCC. The Gene Expression Omnibus datasets were used to identify the upstream transcriptional regulators of SIGLEC10 in tumor-associated macrophages (TAMs) and the downstream biological functions it mediates. These findings were then validated through in vitro and in vivo experiments. The impact of Siglecg deficiency on the efficacy of immunotherapy and the activation of CD8+T cells was analyzed in mouse HNSCC tumor-bearing models.Results The expression of Siglec-G/10, rather than that of Siglec-15, was positively correlated with immune suppressive marker programmed death-ligand 1 (PD-L1) expression and was associated with cervical lymph node metastasis, poorer pathologic stage, and lower sensitivity to immunotherapy. Siglecg deficiency rescued the immune suppressive tumor microenvironment, as evidenced by decreased TAM-associated phenotype and increased CD8+T cell infiltration and activation, which inhibited tumor growth significantly. Single-cell sequence and transcription factor prediction revealed that signal transducer and activator of transcription 6 (STAT6) could induce Siglec-G/10 transcription. Interleukin (IL)-4 could upregulate Siglec-G/10 expression significantly via STAT6 activation, as proved by overexpression and inhibition of STAT6. Signal transduction mechanism revealed that Siglec-G/10 could promote TAM differentiation and activation via increasing HIF1α (hypoxia-inducible factor 1α) expression. Furthermore, Siglecg deficiency could enhance the efficacy of immune checkpoint inhibitor, and increase the infiltration and cytotoxic functions of CD8+T cells.Conclusions Our results suggest that high Siglec-G/10 expression aggravates the immune suppressive tumor microenvironment and impedes the immunotherapy efficacy in HNSCC, which indicates that targeting Siglec-G/10 may represent a promising therapeutic option for improving the immunotherapy efficacy in HNSCC.

OBJECTIVES:The option is rare for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) failed to prior-line immune checkpoint inhibitors (ICIs) and cetuximab-based treatment. The efficacy of salvage therapy was unsatisfied. MATERIALS AND METHODS:We collected the clinical data of R/M HNSCC patients progressed from prior-line immunotherapy and cetuximab therapy, and retrospectively analyzed the efficacy and toxicity of anlotinib-based therapy in these patients. RESULTS:In total, 24 eligible participants were accrued between October 2021 and November 2024. Up to the cutoff time of November 1st, 2024, the objective response rate was 37.5%. Survival analysis revealed the median progression-free survival and overall survival was 4.27 months (95% CI, 1.53-7.01 months) and 8.67 months (95% CI, 5.62-11.72 months), respectively. For the safety, most common TRAEs with any grades were hypertension, hand-foot syndrome, gastrointestinal response, hemorrhage, hepatic dysfunction, and fatigue. Grade 3 or more TRAEs were observed in 3 (12.5%) patients, and no Grade 5 TRAEs were occurred. CONCLUSIONS:Our observations indicated that anlotinib-based therapy had considerable efficacy and well tolerance in R/M HNSCC patients failed to ICIs and cetuximab-based therapy, and might be acted as a novel and potentially effective option in later-line treatment of R/M HNSCC.

Mucosal melanoma (MM) is a rare and aggressive form of melanoma with a poorer prognosis compared to other subtypes. Recent large-scale next-generation sequencing studies, including our own research, have demonstrated that the molecular characteristics and potential oncogenic drivers of MM differ significantly from those of cutaneous melanoma. The emergence of selective CDK4/6 inhibitors, already approved for use in breast cancer and undergoing phase III clinical trials for other solid tumors, represents a promising development in the treatment of MM. Recent studies have shown that CDK4/6 inhibitors not only induce cell cycle arrest but also play a crucial role in facilitating the interaction between tumor cells and the host immune system. Moreover, our findings indicate that dysregulation of cell cycle progression due to cyclin‐dependent kinase 4 (CDK4) amplification is a significant genetic characteristic in a substantial portion of MM cases. Targeting CDK4 in specific MM patients shows promise for precision cancer therapy, utilizing molecularly characterized MM patient-derived xenograft (PDX) models and clinical trials. This paper provides an overview of existing literature on CDK4/6 dysregulation in MM, as well as preclinical and clinical investigations on CDK4/6 inhibitors and potential combination therapies for MM treatment.

AbstractPatients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC) have poor survival outcomes. The real‐world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)‐based chemoradiotherapy in patients with LA‐HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3‐year overall survival (OS) rate. Log‐rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow‐up time was 54.2 (95% confidence interval [CI]: 52.7–55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57–0.99, p = 0.038) and progression‐free survival (PFS) (HR = 0.74, 95% CI: 0.58–0.96, p = 0.021). Subgroup analysis revealed that aged 50–60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab‐related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA‐HNSCC patients in an IMRT era.