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Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial



This prospectively randomised, double-blinded, placebo-controlled, multicenter Phase 3 clinical trial was conducted to assess the efficacy and safety profile of nimotuzumab (nimo) plus concurrent chemo-radiotherapy (CCRT) in patients with unresectable locally advanced ESCC.


Patients were randomly assigned (1:1) to receive CCRT plus nimotuzumab or placebo. The primary endpoint was overall survival (OS). In addition, interim analysis for short-term response rate was pre-defined.


A total of 201 patients were randomised into two groups. Eighty patients in the nimo group and eighty-two in the placebo group were evaluable. Three to six months after treatment, 26 (32.5%) patients achieved complete response (CR) in the nimo group, and 10 (12.2%) in the placebo group (P = 0.002). The ORR of the nimo group was significantly higher than the placebo group (93.8% vs. 72.0%, P < 0.001). The two groups’ grade 3–5 adverse drug reactions were 11.1% vs. 10.9% (P > 0.05).


Nimotuzumab, in combination with chemo-radiotherapy, increased the CRR and ORR with a good safety profile. The OS is needed to be followed and finally analysed.

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Fig. 1: Flowchart.
Fig. 2: Short-term efficacy.
Fig. 3: Subgroup analysis.

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  1. Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999;281:1623–7.

    Article  CAS  PubMed  Google Scholar 

  2. Zeng H, Zheng R, Zhang S, Zuo T, Xia C, Zou X, et al. Esophageal cancer statistics in China, 2011: estimates based on 177 cancer registries. Thorac Cancer. 2016;7:232–7.

    Article  PubMed  Google Scholar 

  3. Murphy AG, Lynch D, Kelly RJ. State of the art management of metastatic gastroesophageal cancer. Ann Transl Med. 2015;3:236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhao L, Li QQ, Zhang R, Xi M, Liao YJ, Qian D, et al. The overexpression of IGFBP-3 is involved in the chemosensitivity of esophageal squamous cell carcinoma cells to nimotuzumab combined with cisplatin. Tumour Biol. 2012;33:1115–23.

    Article  CAS  PubMed  Google Scholar 

  5. You B, Brade A, Magalhaes JM, Siu LL, Oza A, Lovell S, et al. A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies. Investig N Drugs. 2011;29:996–1003.

    Article  CAS  Google Scholar 

  6. van Rossum PSN, Mohammad NH, Vleggaar FP, van Hillegersberg R. Treatment for unresectable or metastatic oesophageal cancer: current evidence and trends. Nat Rev Gastroenterol Hepatol. 2018;15:235–49.

    Article  PubMed  Google Scholar 

  7. Sasaki Y, Kato K. Chemoradiotherapy for esophageal squamous cell cancer. Jpn J Clin Oncol. 2016;46:805–10.

    Article  PubMed  Google Scholar 

  8. Domper Arnal MJ, Ferrández Arenas Á, Lanas Arbeloa Á. Esophageal cancer: risk factors, screening and endoscopic treatment in Western and Eastern countries. World J Gastroenterol. 2015;21:7933–43.

    Article  PubMed  PubMed Central  Google Scholar 

  9. de Castro Jr G, Segalla JG, de Azevedo SJ, Andrade CJ, Grabarz D, de Araújo Lima França B, et al. A randomised phase II study of chemoradiotherapy with or without nimotuzumab in locally advanced oesophageal cancer: NICE trial. Eur J Cancer. 2018;88:21–30.

    Article  CAS  Google Scholar 

  10. Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20:1167–74.

    Article  CAS  PubMed  Google Scholar 

  11. Ajani JA, Winter K, Komaki R, Kelsen DP, Minsky BD, Liao Z, et al. Phase II randomized trial of two nonoperative regimens of induction chemotherapy followed by chemoradiation in patients with localized carcinoma of the esophagus: RTOG 0113. J Clin Oncol. 2008;26:4551–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ramos-Suzarte M, Lorenzo-Luaces P, Lazo NG, Perez ML, Soriano JL, Gonzalez CE, et al. Treatment of malignant, non-resectable, epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiation therapy and chemotherapy. Cancer Biol Ther. 2012;13:600–5.

    Article  CAS  PubMed  Google Scholar 

  13. Mazorra Z, Chao L, Lavastida A, Sanchez B, Ramos M, Iznaga N, et al. Nimotuzumab: beyond the EGFR signaling cascade inhibition. Semin Oncol. 2018;45:18–26.

    Article  CAS  PubMed  Google Scholar 

  14. Rajaram P, Chandra P, Ticku S, Pallavi BK, Rudresh KB, Mansabdar P. Epidermal growth factor receptor: role in human cancer. Indian J Dent Res. 2017;28:687–94.

    Article  PubMed  Google Scholar 

  15. Ramakrishnan MS, Eswaraiah A, Crombet T, Piedra P, Saurez G, Iyer H, et al. Nimotuzumab, a promising therapeutic monoclonal for treatment of tumors of epithelial origin. mAbs. 2009;1:41–8.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Garrido G, Tikhomirov IA, Rabasa A, Yang E, Gracia E, Iznaga N, et al. Bivalent binding by intermediate affinity of nimotuzumab: a contribution to explain antibody clinical profile. Cancer Biol Ther. 2011;11:373–82.

    Article  CAS  PubMed  Google Scholar 

  17. Talavera A, Friemann R, Gómez-Puerta S, Martinez-Fleites C, Garrido G, Rabasa A, et al. Nimotuzumab, an antitumor antibody that targets the epidermal growth factor receptor, blocks ligand binding while permitting the active receptor conformation. Cancer Res. 2009;69:5851–9. Erratum in: Cancer Res. 2009;69:6758.

    Article  CAS  PubMed  Google Scholar 

  18. Chen Y, Wu X, Bu S, He C, Wang W, Liu J, et al. Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma. Cancer Sci. 2012;103:1979–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, et al. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: the NRG oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol. 2017;3:1520–8. Erratum in: JAMA Oncol. 2017;3:1589.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wittrup KD. Antitumor antibodies can drive therapeutic T cell responses. Trends Cancer. 2017;3:615–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Chao L, Pérez D, Sánchez B. Nimotuzumab-mediated antibody-dependent cellular cytotoxicity activity on target tumor cell lines depends on the expression level of the epidermal growth factor receptor. Biotecnolía Aplicada. 2017;34:1201–5.

    Google Scholar 

  22. Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, et al. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 2021;17:1143–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yu R, Wang W, Li T, Li J, Zhao K, Wang W, et al. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021;17:4081–9.

    Article  CAS  PubMed  Google Scholar 

  24. Luhua W, Ming C, Ken K, Lucjan W, Elizabeth CS, Anastasia J, et al. A phase 3 randomized, double-blind, placebocontrolled, multicenter, global study of durvalumab with and after chemoradiotherapy in patients with locally advanced, unresectable esophageal squamous cell carcinoma: KUNLUN. 2022;ASCO-GI:abstract TPS373.

  25. Zhang W, Yan C, Gao X, Li X, Cao F, Zhao G, et al. Safety and feasibility of radiotherapy plus camrelizumab for locally advanced esophageal squamous cell carcinoma. Oncologist. 2021;26:e1110–e1124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This study has been presented as a poster discussion at the 2022 American Society of Clinical Oncology Annual Meeting (Abstract No: 4016). Many thanks to all the patients and their families. Thank all the caregivers, investigators, and site personnel.


The authors received no specific funding for this work.

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Authors and Affiliations



The authors confirm contribution to the paper as follows: study conception and design: JY, XM, AZ and JW; data collection: XM, AZ, JW, X Wu, GL, JZ, HM, XZ, AS, CD, SY, BWg, ZQ, CH, XS, MY, RF, NH and X Wang; analysis and interpretation of results: XM, AZ and JW; draft manuscript preparation: XM and JY. All authors reviewed the results and approved the final version of the manuscript.

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Correspondence to Jinming Yu.

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The authors declare no competing interests.

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This study was conducted in accordance with the Declaration of Helsinki. All patients gave their written informed consent. The institutional ethics committees at each site approved the protocol.

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Meng, X., Zheng, A., Wang, J. et al. Nimotuzumab plus concurrent chemo-radiotherapy in unresectable locally advanced oesophageal squamous cell carcinoma (ESCC): interim analysis from a Phase 3 clinical trial. Br J Cancer 129, 1787–1792 (2023).

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