Abstract
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.
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The deidentified individual participant data generated and analyzed in this study cannot be made publicly available due to patient privacy restrictions and ethical regulations. These data, along with the statistical analysis plan (included in Supplementary information) and a data dictionary, may be made available to qualified researchers upon reasonable request for non-commercial academic purposes upon reasonable request, subject to approval by the study steering committee and the institutional review board of Sun Yat-sen University Cancer Centre. Access will require a signed data-sharing agreement. Requests should be submitted in writing to the corresponding author (H.-Q.M.) and will be initially reviewed within 12 weeks. If approved, data provision will be arranged within 6 weeks after the execution of the data-sharing agreement, unless otherwise specified in the agreement. The study protocol is included in the Supplementary Information file. All other data supporting this work are included in the main article, supplementary, or source data file. Source data for figures and tables are provided with this paper. Source data are provided with this paper.
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Acknowledgements
The Elsevier Language Editing Service was used to assist with manuscript editing during drafting. This study was funded by grants from the National Key Research and Development Programme of China (2022YFC2505800, and 2022YFC2705005), National Natural Science Foundation of China (82173287, 82372980, 82203776, 82203125, 82222050, 82272739, 82272882, 82073003, 82003267, 82002852, 82373258, 82361168664, 8247101588, 82473038, and 32200651), Guangdong Basic and Applied Basic Research Foundation (2021B1515230002, and 2023B1515120092), Science and Technology Programme of Guangzhou (202201011561, 2023A04J2127, and 2024B03J1248), Sun Yat-sen University Clinical Research 5010 Programme (2024003, 2015021, 2019023, and 2017010), Postdoctoral Innovative Talent Support Programme (BX20220361), Planned Science and Technology Project of Guangdong Province (2019B020230002), Key Youth Teacher Cultivating Programme of Sun Yat-sen University (20ykzd24), and Fundamental Research Funds for the Central Universities.
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H.-Q.M. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. L.-T.L., X.-S.S., T.-T.Q., X.-Y.L., L.G., and H.-Y.M. contributed equally to this work. H.-Q.M., L.-Q.T., and Q.-Y.C. jointly supervised this work. Concept and design: L.-T.L., H.-Q.M., L.-Q.T., Q.-Y.C. Acquisition, analysis, or interpretation of data: L.-T.L., X.-S.S., T.-T.Q., X.-Y.L., L.G., H.-Y.M. Drafting of the manuscript: L.-T.L., X.-S.S., S.-S.G., S.-L.L., Y.H., D.-H.L., R.S. Critical review of the manuscript for important intellectual content: L.-T.L., X.-S.S., G.-D.J., J.-B.L., Q.L., P.W., Y.-J.L., J.C., Y.-F.L. Statistical analysis: L.-T.L., H.C., W.-X.X. Administrative, technical, or material support: F.Q., J.-H.Y. Trial management and toxicity review: Q.Y, D.-X.W., J.-J.Y., C.Z. Obtained funding: H.-Q.M. Supervision: Q.-Y.C., L.-Q.T., H.-Q.M.
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Liu, LT., Sun, XS., Quan, TT. et al. Concurrent chemoradiotherapy plus nimotuzumab versus chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma with a suboptimal response to induction chemotherapy: a randomized phase 2 trial. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71019-5
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DOI: https://doi.org/10.1038/s41467-026-71019-5
