Long-Term Survival of Patients With Chemotherapy-Naïve Metastatic Nasopharyngeal Carcinoma Receiving Cetuximab Plus Docetaxel and Cisplatin Regimen

Purpose: Metastatic nasopharyngeal carcinoma (mNPC) remains incurable. This prospective study aimed to investigate whether adding cetuximab to cisplatin-based induction therapy could improve efficacy and survival for chemotherapy-naïve mNPC patients. Patients and Methods: Eligible chemotherapy-naïve mNPC patients were enrolled, including those initially diagnosed with mNPC (IM) and those with first-relapse metastases after radiotherapy (RM). Patients all received induction chemotherapy (IC) including docetaxel and cisplatin plus cetuximab. Those who obtained objective remission after IC would continue to receive radiotherapy concurrent with cetuximab and cisplatin, and further capecitabine as maintenance. Contemporaneous patients who received conventional therapy served as controls. Results: Forty-three patients were enrolled, including 17 IM and 26 RM patients. Thirty-nine (90.7%) patients had WHO III subtype. The overall response and complete response (CR) rates were, respectively, 79.1 and 34.9% after induction therapy and 76.7 and 46.5% after chemoradiotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) rates reached 34.9 and 30%, respectively. Subgroup analysis showed that compared with RM patients, IM patients had a higher 5-year OS (58.8 vs. 19.2%) and PFS (52.9 vs. 19.2%). The IM group had a higher CR rate of induction treatment than the RM group (52.9 vs. 23.1%). No treatment-related death was observed. Twelve patients (27.9%) remained alive with disease-free survival times from 60+ to 135+ months. Control patients showed a substantially lower survival rate (5-year OS, 10.9%) and few long-term survivors. Conclusions: This regimen resulted in significantly improved efficacy and survival, which indicates a potentially curative role for chemotherapy-naïve mNPC, especially in newly diagnosed patients. A phase III clinical trial (NCT02633176) is ongoing for confirmation.

[1]  B. Costello,et al.  Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  Chiun Hsu,et al.  Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. , 2017, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  Yihai Cao,et al.  Maintenance of antiangiogenic and antitumor effects by orally active low-dose capecitabine for long-term cancer therapy , 2017, Proceedings of the National Academy of Sciences.

[4]  Jianji Pan,et al.  Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial , 2016, The Lancet.

[5]  G. Masi,et al.  Safety profile of capecitabine as maintenance treatment after induction with XELOX or FOLFOX in metastatic colorectal cancer patients. , 2016, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  Edwin P Hui,et al.  Nasopharyngeal carcinoma , 2016, The Lancet.

[7]  D. Tindall,et al.  Androgen Receptor Upregulation Mediates Radioresistance after Ionizing Radiation. , 2015, Cancer research.

[8]  C. Schumann,et al.  Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. , 2015, The Lancet. Oncology.

[9]  C. Mathers,et al.  Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012 , 2015, International journal of cancer.

[10]  H. Minn,et al.  Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. , 2015, The Lancet. Oncology.

[11]  Ying Huang,et al.  Retrospective Analysis of 234 Nasopharyngeal Carcinoma Patients with Distant Metastasis at Initial Diagnosis: Therapeutic Approaches and Prognostic Factors , 2014, PloS one.

[12]  Z. Martina,et al.  The efficiency of tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia exposed to ionizing radiation due to the Chornobyl nuclear power plant accident. , 2014, Problemy radiatsiinoi medytsyny ta radiobiolohii.

[13]  R. Sun,et al.  Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis , 2013, Chinese journal of cancer.

[14]  Li-Zhi Liu,et al.  Prospective study of tailoring whole-body dual-modality [18F]fluorodeoxyglucose positron emission tomography/computed tomography with plasma Epstein-Barr virus DNA for detecting distant metastasis in endemic nasopharyngeal carcinoma at initial staging. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  S. Faivre,et al.  Cisplatin and fluorouracil with or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. , 2013, The Lancet. Oncology.

[16]  W. Guo,et al.  Efficacy of Nimotuzumab Combined with Docetaxel–Cisplatin–Fluorouracil Regimen in Treatment of Advanced Oral Carcinoma , 2013, Cell Biochemistry and Biophysics.

[17]  Jianji Pan,et al.  Combined High-dose Radiation Therapy and Systemic Chemotherapy Improves Survival in Patients With Newly Diagnosed Metastatic Nasopharyngeal Cancer , 2012, American journal of clinical oncology.

[18]  Wen-Qi Jiang,et al.  Comparison of five cisplatin-based regimens frequently used as the first-line protocols in metastatic nasopharyngeal carcinoma , 2012, Journal of Cancer Research and Clinical Oncology.

[19]  A. King,et al.  A phase II study of concurrent cetuximab-cisplatin and intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma. , 2012 .

[20]  Chaosu Hu,et al.  8558 POSTER An Open, Multicenter Clinical Study of Cetuximab Combined With Intensity Modulated Radiotherapy Plus Concurrent Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma , 2011 .

[21]  Mauro D'Amico,et al.  Duration of chemotherapy for metastatic breast cancer: a systematic review and meta-analysis of randomized clinical trials. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  J. Fay,et al.  Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. , 2011, The oncologist.

[23]  Chetana Basavaraj,et al.  Nimotuzumab with chemoradiation confers a survival advantage in treatment-naïve head and neck tumors over expressing EGFR , 2010, Cancer biology & therapy.

[24]  M. Frómeta,et al.  Nimotuzumab plus radiotherapy for unresectable squamous-cell carcinoma of the head and neck , 2010, Cancer biology & therapy.

[25]  Jordi Giralt,et al.  Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. , 2010, The Lancet. Oncology.

[26]  C. Bokemeyer,et al.  Platinum-based chemotherapy plus cetuximab in head and neck cancer. , 2008, The New England journal of medicine.

[27]  Fenghua Wang,et al.  Phase II study of capecitabine and cisplatin combination as first-line chemotherapy in Chinese patients with metastatic nasopharyngeal carcinoma , 2008, Cancer Chemotherapy and Pharmacology.

[28]  K. Nishio,et al.  Antibody‐dependent cellular cytotoxicity of cetuximab against tumor cells with wild‐type or mutant epidermal growth factor receptor , 2007, Cancer science.

[29]  C. Lui,et al.  Treatment outcomes of patients with AJCC stage IVC nasopharyngeal carcinoma: benefits of primary radiotherapy. , 2006, Japanese journal of clinical oncology.

[30]  Christopher U. Jones,et al.  Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. , 2006, The New England journal of medicine.

[31]  M. Goldwasser,et al.  Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[32]  J. Sham,et al.  A phase II study of docetaxel and cisplatin as first-line chemotherapy in patients with metastatic nasopharyngeal carcinoma. , 2005, Oral oncology.

[33]  J. Whang‐Peng,et al.  Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  T. Poon,et al.  Antitumor effect and enhancement of cytotoxic drug activity by cetuximab in nasopharyngeal carcinoma cells. , 2005, In vivo.

[35]  Armando Santoro,et al.  Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. , 2004, The New England journal of medicine.

[36]  T. Poon,et al.  Prognostic significance of tumor angiogenesis, Ki 67, p53 oncoprotein, epidermal growth factor receptor and HER2 receptor protein expression in undifferentiated nasopharyngeal carcinoma—a prospective study , 2003, Head & neck.

[37]  C. Law,et al.  Combination gemcitabine and cisplatin chemotherapy for metastatic or recurrent nasopharyngeal carcinoma: report of a phase II study. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[38]  J. Armand,et al.  Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[39]  John M. Lachin,et al.  Biostatistical Methods: The Assessment of Relative Risks , 2000 .

[40]  C. Perez,et al.  Carcinoma of the nasopharynx: factors affecting prognosis. , 1992, International journal of radiation oncology, biology, physics.

[41]  J J Shuster,et al.  Median follow-up in clinical trials. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.