TARGETING EGFR DURING CHEMORADIOTHERAPY FOR HEAD AND NECK CANCER: THE EVOLVING ROLE OF NIMOTUZUMAB

Abstract

Background: Concurrent cisplatin-based radiotherapy is the standard curative treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC); however, treatment failure remains common. Epidermal growth factor receptor (EGFR) contributes to tumor proliferation, DNA damage repair, and radioresistance. Nimotuzumab is a humanized anti-EGFR IgG1 antibody whose intermediate affinity and requirement for bivalent binding may favor tumor-selective activity with limited severe dermatologic toxicity. Objective: To critically review the biological rationale, clinical efficacy, safety, and unresolved questions surrounding the use of nimotuzumab in HNSCC. Methods: PubMed/MEDLINE, ClinicalTrials.gov, oncology journal websites, and reference lists were searched for English-language reports available until July 2026. Randomized trials and systematic reviews were prioritized, while non-randomized studies were used to contextualize the activity, safety, and feasibility. This was a narrative rather than a systematic review compliant with the PRISMA guidelines. Results: A randomized phase IIb study reported improved response and five-year survival when nimotuzumab was added to chemoradiotherapy, although its small sample size and factorial design limited precision. In a randomized phase III trial involving 536 patients, weekly nimotuzumab 200 mg added to radiotherapy and weekly 30 mg/m ² cisplatin improved progression-free survival (hazard ratio [HR] 0.69), locoregional control (HR 0.67), and disease-free survival (HR 0.71). A prespecified 2024 long-term conference report, at a median follow-up of 8.86 years, showed higher 10-year overall survival with nimotuzumab-chemoradiotherapy than with chemoradiotherapy alone (33.5% versus 22.5%; HR 0.811, 95% confidence interval 0.664–0.995; P=0.044), without a significant increase in late adverse events. A favorable survival signal was observed in HPV-negative oropharyngeal cancer, although the small HPV-positive population precluded a reliable comparison by HPV status. A meta-analysis of seven randomized trials involving 1,012 patients also favored nimotuzumab for survival and tumor response outcomes; however, clinical and geographic heterogeneity limited generalizability. Evidence in postoperative and recurrent/metastatic settings remains inconclusive or nonrandomized. Conclusion: The addition of nimotuzumab to weekly cisplatin-based definitive chemoradiotherapy improved disease control and may provide a long-term survival benefit, particularly in predominantly HPV-negative populations. Nevertheless, cisplatin-based radiotherapy remains the standard curative treatment. Broader adoption requires full peer-reviewed reporting of mature survival results, multicenter validation using contemporary treatment schedules, and prospective biomarker-based patient selection.