Research progress on anti-EGFR targeted therapy and immunotherapy for locally advanced nasopharyngeal carcinoma

doi:10.3760/cma.j.cn371439-20260318-00098

Abstract

Abstract:

In recent years，preliminary therapeutic efficacy of epidermal growth factor receptor inhibitors including cetuximab and nimotuzumab has been observed in the treatment of locally advanced nasopharyngeal carcinoma （LANPC）. Multiple clinical investigations on immunotherapy for LANPC have been conducted around strategies such as whole-course intensification，adjuvant consolidation，cisplatin-sparing detoxification regimens，and stratified intensification for high-risk populations. Exploration of therapeutic strategy optimization guided by biomarkers and novel combination regimens will facilitate the further clinical application of targeted therapy and immunotherapy in LANPC patients.

Key words: Nasopharyngeal carcinoma, Molecular targeted therapy, Immunotherapy, Immune checkpoint inhibitors

Zhao Bingying, Wen Miaowei, Hu Shanliang, Wang Yang, Song Yipeng. Research progress on anti-EGFR targeted therapy and immunotherapy for locally advanced nasopharyngeal carcinoma[J]. Journal of International Oncology, 2026, 53(10): 623-627.

References 44

[1]	Colevas AD, Cmelak AJ, Pfister DG, et al. NCCN guidelines^® insights: head and neck cancers, version 2.2025[J]. J Natl Compr Canc Netw, 2025, 23(2): 2-11. DOI: 10.6004/jnccn.2025.0007.
[2]	Zhang Y, Gu S, Deng H, et al. Global epidemiological profile in nasopharyngeal carcinoma: a prediction study[J]. BMJ Open, 2024, 14(12): e091087. DOI: 10.1136/bmjopen-2024-091087.
[3]	Liao C, Liu H, Luo X. The emerging roles of exosomal miRNAs in nasopharyngeal carcinoma[J]. Am J Cancer Res, 2021, 11(6): 2508-2520. pmid: 34249413
[4]	Dai J, Zhang B, Su Y, et al. Induction chemotherapy followed by radiotherapy vs chemoradiotherapy in nasopharyngeal carcinoma: a randomized clinical trial[J]. JAMA Oncol, 2024, 10(4): 456-463. DOI: 10.1001/jamaoncol.2023.6552. pmid: 38329737
[5]	Cai M, Wang Y, Ma H, et al. Advances and challenges in immunotherapy for locally advanced nasopharyngeal carcinoma[J]. Cancer Treat Rev, 2024, 131: 102840. DOI: 10.1016/j.ctrv.2024.102840.
[6]	Kang JJ, Ko A, Kil SH, et al. EGFR pathway targeting drugs in head and neck cancer in the era of immunotherapy[J]. Biochim Biophys Acta Rev Cancer, 2023, 1878(1): 188827. DOI: 10.1016/j.bbcan.2022.188827.
[7]	Wang Z, Zhou T, Chen X, et al. CCDC86 promotes the aggressive behavior of nasopharyngeal carcinoma by positively regulating EGFR and activating the PI3K/Akt signaling[J]. Neoplasma, 2023, 70(6): 761-776. DOI: 10.4149/neo_2023_221021N1039. pmid: 38247332
[8]	Wu Y, Jia Q, Tang Q, et al. A specific super-enhancer actuated by berberine regulates EGFR-mediated RAS-RAF1-MEK1/2-ERK1/2 pathway to induce nasopharyngeal carcinoma autophagy[J]. Cell Mol Biol Lett, 2024, 29(1): 92. DOI: 10.1186/s11658-024-00607-4. pmid: 38943090
[9]	Wang J, Shang Y, Wang Y, et al. Nasopharyngeal carcinoma with non-squamous phenotype may be a variant of nasopharyngeal squamous cell carcinoma after inhibition of EGFR/PI3K/AKT/mTOR pathway[J]. Histol Histopathol, 2024, 39(5): 647-657. DOI: 10.14670/HH-18-673.
[10]	Zhang Y. Targeting epidermal growth factor receptor for cancer treatment: abolishing both kinase-dependent and kinase-independent functions of the receptor[J]. Pharmacol Rev, 2023, 75(6): 1218-1232. DOI: 10.1124/pharmrev.123.000906. pmid: 37339882
[11]	Xiong Q, Wen H, Wang J, et al. Applications and challenges of EGFR inhibitors in the treatment of nasopharyngeal carcinoma[J]. Biochem Biophys Res Commun, 2025, 788: 152826. DOI: 10.1016/j.bbrc.2025.152826.
[12]	Lacouture ME, Wainberg ZA, Patel AB, et al. Reducing skin toxicities from EGFR inhibitors with topical BRAF inhibitor therapy[J]. Cancer Discov, 2021, 11(9): 2158-2167. DOI: 10.1158/2159-8290.CD-20-1847. pmid: 33910927
[13]	Zhu Q, Duan XB, Hu H, et al. EBV-induced upregulation of CD55 reduces the efficacy of cetuximab treatment in nasopharyngeal carcinoma[J]. J Transl Med, 2024, 22(1): 1111. DOI: 10.1186/s12967-024-05822-3. pmid: 39695702
[14]	Peng X, Zhou Y, Tao Y, et al. Nasopharyngeal carcinoma: the role of the EGFR in Epstein-Barr virus infection[J]. Pathogens, 2021, 10(9): 1113. DOI: 10.3390/pathogens10091113.
[15]	Zeng MC, Jia QJ, Xu J, et al. The whole-blood Epstein-Barr virus DNA can serve as a valuable molecular marker for diagnosis and prognosis prediction of nasopharyngeal carcinoma[J]. Am J Cancer Res, 2023, 13(11): 5431-5442.
[16]	中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)鼻咽癌诊疗指南2025[M]. 北京: 人民卫生出版社, 2025.
[17]	Yang Y, Zhou H, Tang L, et al. Izalontamab brengitecan, an EGFR and HER3 bispecific antibody-drug conjugate, versus chemotherapy in heavily pretreated recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 study in China[J]. Lancet, 2025, 406(10516): 2235-2243. DOI: 10.1016/S0140-6736(25)01954-3.
[18]	Han F, Lv X, Zhou YJ, et al. Becotatug vedotin, MRG003, in previously treated recurrent or metastatic nasopharyngeal carcinoma: a multicenter, single-arm, phase Ⅱa trial[J]. Med, 2026, 7(4): 101029. DOI: 10.1016/j.medj.2026.101029.
[19]	Bai Y, Lei H, Gou S, et al. Bispecific antibody-drug conjugates: a modular blueprint for next-generation cancer therapeutics[J]. Arch Pharm Res, 2026, 49(1): 61-100. DOI: 10.1007/s12272-026-01595-z.
[20]	Rodriguez-Castellanos VE, Quintana JM, Martin JM, et al. Radiation- triggered payload release enhances bispecific antibody efficacy[J]. Cancer Res, 2026, 86(2): 453-466. DOI: 10.1158/0008-5472.CAN-25-0517.
[21]	Okamoto K, Ando T, Izumi H, et al. AXL activates YAP through the EGFR-LATS1/2 axis and confers resistance to EGFR-targeted drugs in head and neck squamous cell carcinoma[J]. Oncogene, 2023, 42(39): 2869-2877. DOI: 10.1038/s41388-023-02810-7. pmid: 37591955
[22]	Wang H, Zhan Y, Luo J, et al. Unveiling immune resistance mechanisms in nasopharyngeal carcinoma and emerging targets for anti-tumor immune response: tertiary lymphoid structures[J]. J Transl Med, 2025, 23(1): 38. DOI: 10.1186/s12967-024-05880-7.
[23]	Liu X, Zhang Y, Yang KY, et al. Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial[J]. Lancet, 2024, 403(10445): 2720-2731. DOI: 10.1016/S0140-6736(24)00594-4. pmid: 38824941
[24]	Liang YL, Liu X, Shen LF, et al. Adjuvant PD-1 blockade with camrelizumab for nasopharyngeal carcinoma: the DIPPER randomized clinical trial[J]. JAMA, 2025, 333(18): 1589-1598. DOI: 10.1001/jama.2025.1132.
[25]	Makowska A, Lelabi N, Nothbaum C, et al. Radiotherapy combined with PD-1 inhibition increases NK cell cytotoxicity towards naso-pharyngeal carcinoma cells[J]. Cells, 2021, 10(9): 2458. DOI: 10.3390/cells10092458.
[26]	DIAMOND Study Group, Xu C, Liang XY, et al. Toripalimab combination therapy without concurrent cisplatin for nasopharyngeal carcinoma: the DIAMOND randomized clinical trial[J]. JAMA, 2025, 334(11): 973-983. DOI: 10.1001/jama.2025.13205.
[27]	Xu C, Zhou GQ, Li WF, et al. Nivolumab combined with induction chemotherapy and radiotherapy in nasopharyngeal carcinoma: a multicenter phase 2 PLATINUM trial[J]. Cancer cell, 2025, 43(5): 925-936. DOI: 10.1016/j.ccell.2025.01.014.
[28]	罗文肖, 吴德华, 蔡隆梅. 免疫疗效生物标志物在鼻咽癌治疗中的预测价值[J]. 国际肿瘤学杂志, 2021, 48(12): 743-746. DOI: 10.3760/cma.j.cn371439-20201120-00147.
[29]	Liu SL, Li XY, Yang JH, et al. Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-centre, double-blind, placebo-controlled, phase 2 trial[J]. Lancet Oncol, 2024, 25(12): 1563-1575. DOI: 10.1016/S1470-2045(24)00504-7.
[30]	You R, Xu GQ, Ding X, et al. Standard chemoradiotherapy with concurrent and adjuvant camrelizumab in patients with high risk nasopharyngeal carcinoma: multicentre, randomised, open label, phase 3 trial[J]. BMJ, 2026, 392: e085863. DOI: 10.1136/bmj-2025-085863.
[31]	Wu KP, Luo XQ, Tan PX, et al. Incidence and spectrum of immune- related adverse events in nasopharyngeal carcinoma patients treated with immune checkpoint inhibitors[J]. Med, 2026, 7(3): 100988. DOI: 10.1016/j.medj.2025.100988.
[32]	Zhang W, Meng Y, Zhang P, et al. PD-1 inhibitor combined with TPF induction chemotherapy in locally advanced nasopharyngeal carcinoma: a retrospective study of efficacy and safety[J]. Front Immunol, 2025, 16: 1654616. DOI: 10.3389/fimmu.2025.1654616.
[33]	Liang H, Jiang YF, Liu GY, et al. Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N₃ nasopharyngeal carcinoma: a phase 2 clinical trial[J]. Nat Commun, 2024, 15(1): 1029. DOI: 10.1038/s41467-024-45126-0. pmid: 38310101
[34]	Jia H, Wang J, Zhang L, et al. Short-course PD-1 blockade in locally advanced nasopharyngeal carcinoma: a phase Ⅱ randomized trial protocol (Tori-013)[J]. Front Immunol, 2025, 16: 1633243. DOI: 10.3389/fimmu.2025.1633243.
[35]	Wang C, Chen J, Li J, et al. An EBV-related CD4 TCR immunotherapy inhibits tumor growth in an HLA-DP5⁺ nasopharyngeal cancer mouse model[J]. J Clin Invest, 2024, 134(8): e172092. DOI: 10.1172/JCI172092.
[36]	Wang G, Mudgal P, Wang L, et al. TCR repertoire characteristics predict clinical response to adoptive CTL therapy against nasopharyngeal carcinoma[J]. Oncoimmunology, 2021, 10(1): 1955545. DOI: 10.1080/2162402X.2021.1955545.
[37]	Baliton M, Alfatlawi D, Attarian S, et al. Therapeutic vaccines for head and neck squamous cell carcinoma and nasopharyngeal carcinoma[J]. Vaccines (Basel), 2026, 14(4): 321. DOI: 10.3390/vaccines14040321.
[38]	Liu Y, Lui KS, Ye Z, et al. EBV latent membrane protein 1 augments γδ T cell cytotoxicity against nasopharyngeal carcinoma by induction of butyrophilin molecules[J]. Theranostics, 2023, 13(2): 458-471. DOI: 10.7150/thno.78395. pmid: 36632221
[39]	Smith C, McGrath M, Neller MA, et al. Complete response to PD-1 blockade following EBV-specific T-cell therapy in metastatic nasopharyngeal carcinoma[J]. NPJ Precis Oncol, 2021, 5(1): 24. DOI: 10.1038/s41698-021-00162-7. pmid: 33742086
[40]	Chen H, Duan X, Deng X, et al. EBV-upregulated B7-H3 inhibits NK cell-mediated antitumor function and contributes to nasopharyngeal carcinoma progression[J]. Cancer Immunol Res, 2023, 11(6): 830-846. DOI: 10.1158/2326-6066.CIR-22-0374.
[41]	Chun KS, Kim DHE, Raut PK, et al. Anticancer natural products targeting immune checkpoint protein network[J]. Semin Cancer Biol, 2022, 86(Pt 3): 1008-1032. DOI: 10.1016/j.semcancer.2021.11.006.
[42]	Dong L, Wang Y, Yao X, et al. Novel insights of anti-EGFR therapy in HNSCC: combined with immunotherapy or not?[J]. Curr Oncol Rep, 2023, 25(2): 93-105. DOI: 10.1007/s11912-022-01349-2. pmid: 36585960
[43]	Mao Y, He Y, Wu L, et al. Induction chemotherapy plus PD-1 blockade and nimotuzumab for locoregionally advanced nasopharyngeal carcinoma: a propensity-matched retrospective study[J]. Jpn J Clin Oncol, 2026, 56(3): 290-298. DOI: 10.1093/jjco/hyaf213.
[44]	Chen K, Huang X, Chen J, et al. Efficacy and safety of combined PD-1 inhibitor with induction chemotherapy followed by IMRT plus nimotuzumab in locally advanced nasopharyngeal carcinoma: a retrospective analysis[J]. Onco Targets Ther, 2025, 18: 283-296. DOI: 10.2147/OTT.S503674.