Skip to main content

Advertisement

SpringerLink
Log in

Real-world clinical outcomes and prognostic factors in Japanese patients with recurrent or metastatic squamous cell carcinoma of head and neck treated with chemotherapy plus cetuximab: a prospective observation study (JROSG12-2)

  • Original Article
  • Published:
International Journal of Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

The aims of this study are to evaluate the efficacy and safety of first-line treatment with chemotherapy plus cetuximab in real-world patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RM-SCCHN) and to identify prognostic factors for overall survival (OS).

Methods

This is a prospective observation study involving 20 oncology institutions in Japan. Patients with RM-SCCHN treated with a first-line therapy consisting of cetuximab plus any chemotherapy regimen between December 2013 and February 2017 were enrolled. The primary objective of the study was 1-year OS. Secondary objectives included response rate and adverse events.

Results

Of 120 patients recruited, 114 patients were analyzed. Median age was 64 years. Cetuximab in combination with platinum plus 5-FU (EXTREME regimen) was chosen in 86 patients (75.4%). The median OS was 12.4 months. A point estimate of the 1-year survival rate was 51.1%. Overall response rate was 26.3%. Grade 3 or worse adverse events included neutropenia (22.8%), hypokalemia (9.6%), acneiform rash (7.0%), pneumonitis (1.8%), and infusion-related reaction (0.9%). On multivariate analysis, regional lymph node metastasis, absence of intervention by dermatologists, lack of response to therapy, skin metastasis, and non-EXTREME regimen were identified as independent unfavorable prognostic factors for OS.

Conclusion

The combination of cetuximab plus chemotherapy was tolerable and efficacious in patients with RM-SCCHN in a real-world setting. Clinical outcomes and prognostic factors extracted from this study provide a reference of the current clinical practice as well as for the future development of novel therapy in RM-SCCHN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Baxi S, Fury M, Ganly I et al (2012) Ten years of progress in head and neck cancers. J Natl Compr Canc Netw 10:806–810

    Article  CAS  Google Scholar 

  2. Jacobs C, Lyman G, Velez-García E et al (1992) A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10:257–263

    Article  CAS  Google Scholar 

  3. Forastiere AA, Metch B, Schuller DE et al (1992) Randomized comparison of cisplatin plus fluorouracil and carboplatin plus fluorouracil versus methotrexate in advanced squamous-cell carcinoma of the head and neck. J Clin Oncol 10:1245–1251

    Article  CAS  Google Scholar 

  4. Grandis JR, Melhem MF, Gooding WE et al (1998) Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival. J Natl Cancer Inst 90:824–832

    Article  Google Scholar 

  5. Egloff AM, Grandis J (2006) Epidermal growth factor receptor-targeted molecular therapeutics for head and neck squamous cell carcinoma. Expert Opin Ther Targets 10:639–647

    Article  CAS  Google Scholar 

  6. Chung CH, Ely K, McGavran L et al (2006) Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 24:4170–4176

    Article  CAS  Google Scholar 

  7. Vermorken JB, Mesia R, Rivera F et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116–1127

    Article  CAS  Google Scholar 

  8. Yoshino T, Hasegawa Y, Takahashi S et al (2013) Platinum-based chemotherapy plus cetuximab for the first-line treatment of Japanese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: results of a phase II trial. Jpn J Clin Oncol 43:524–531

    Article  Google Scholar 

  9. Burtness B, Harrington KJ, Greil R et al (2019) Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet 394:1915–1928

    Article  CAS  Google Scholar 

  10. Ferris RL, Blumenschein G Jr, Fayette J et al (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867

    Article  Google Scholar 

  11. Vermorken JB, Trigo J, Hitt R et al (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25:2171–2177

    Article  CAS  Google Scholar 

  12. Hitt R, Irigoyen A, Cortes-Funes H et al (2012) Phase II study of the combination of cetuximab and weekly paclitaxel in the first-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. Ann Oncol 23:1016–1022

    Article  CAS  Google Scholar 

  13. Bernad IP, Trufero JM, Urquizu LC et al (2017) Activity of weekly paclitaxel-cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors. Clin Transl Oncol 19:769–776

    Article  CAS  Google Scholar 

  14. Knoedler M, Gauler TC, Gruenwald V et al (2013) Phase II study of cetuximab in combination with docetaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck after platinum-containing therapy: a multicenter study of the Arbeitsgemeinschaft Internistische Onkologie. Oncology 84:284–289

    Article  CAS  Google Scholar 

  15. Posch D, Fuchs H, Kornek G et al (2016) Docetaxel plus cetuximab biweekly is an active regimen for the first-line treatment of patients with recurrent/metastatic head and neck cancer. Sci Rep 6:32946

    Article  CAS  Google Scholar 

  16. Tahara M, Kiyota N, Yokota T et al (2018) Phase II trial of combination treatment with paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (CSPOR-HN02). Ann Oncol 29:1004–1009

    Article  CAS  Google Scholar 

  17. Freemantle N, Strack T (2010) Real-world effectiveness of new medicines should be evaluated by appropriately designed clinical trials. J Clin Epidemiol 63:1053–1058

    Article  Google Scholar 

  18. Berger ML, Lipset C, Gutteridge A et al (2015) Optimizing the leveraging of real-world data to improve the development and use of medicines. Value Health 18:127–130

    Article  Google Scholar 

  19. Depenni R, Cossu Rocca M, Ferrari D et al (2019) Clinical outcomes and prognostic factors in recurrent and/or metastatic head and neck cancer patients treated with chemotherapy plus cetuximab as first-line therapy in a real-world setting. Eur J Cancer 115:4–12

    Article  Google Scholar 

  20. Bossi P, Resteghini C, Paielli N et al (2016) Prognostic and predictive value of EGFR in head and neck squamous cell carcinoma. Oncotarget 7:74362–74379

    Article  Google Scholar 

  21. Argiris A, Li Y, Forastiere A (2004) Prognostic factors and long-term survivorship in patients with recurrent or metastatic carcinoma of the head and neck. Cancer 101:2222–2229

    Article  Google Scholar 

  22. Van Cutsem E, Tejpar S, Vanbeckevoort D et al (2012) Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol 30:2861–2868

    Article  Google Scholar 

  23. Bonner JA, Harari PM, Giralt J et al (2010) 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 [published correction appears in Lancet Oncol 2010 Jan; 11(1):14]. Lancet Oncol 11:21–28

    Article  CAS  Google Scholar 

  24. Qi WX, Fu S, Zhang Q et al (2014) Incidence and risk of severe infections associated with anti-epidermal growth factor receptor monoclonal antibodies in cancer patients: a systematic review and meta-analysis. BMC Med 12:203

    Article  Google Scholar 

  25. Burtness B, Goldwasser MA, Flood W et al (2005) Eastern Cooperative Oncology Group. 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. J Clin Oncol 23:8646–8654

    Article  Google Scholar 

  26. Vermorken JB, Stöhlmacher-Williams J, Davidenko I et al (2013) 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. Lancet Oncol 14:697–710

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Japanese Radiation Oncology Study Group (JROSG) and financially supported by Merck Biopharma. We thank all participating patients and investigators for their support of the study, and gratefully acknowledge the help of all staff at the Clinical Research Institute, National Hospital Organization Kyushu Cancer Center, with study coordination and data collection.

Funding

This work was supported by Merck Biopharma.

Author information

Authors and Affiliations

  1. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi, Sunto-gun, Shizuoka, 411-8777, Japan

    Tomoya Yokota

  2. Department of Radiation Oncology, Hyogo Cancer Center Hospital, Akashi, Hyogo, Japan

    Yosuke Ota

  3. Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Hirofumi Fujii

  4. Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Japan

    Takeshi Kodaira

  5. Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Mototsugu Shimokawa

  6. Department of Otolaryngology, Kyushu Medical Center, Fukuoka, Japan

    Torahiko Nakashima

  7. Department of Head and Neck Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan

    Nobuya Monden

  8. Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Akihiro Homma

  9. Department of Medical Oncology, Kindai University Nara Hospital, Ikoma, Japan

    Shinya Ueda

  10. Department of Radiation Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Tetsuo Akimoto

Authors
  1. Tomoya Yokota
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yosuke Ota
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hirofumi Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takeshi Kodaira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mototsugu Shimokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Torahiko Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nobuya Monden
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akihiro Homma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shinya Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tetsuo Akimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomoya Yokota.

Ethics declarations

Conflict of interest

Dr. Yokota serves in an advisory role for Merck Biopharma, MSD, and Rakuten Medical, and has received lecture fees from Merck Biopharma, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb, AstraZeneca, Chugai, MSD, and Eisai. All authors received research funding from Merck Biopharma.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yokota, T., Ota, Y., Fujii, H. et al. Real-world clinical outcomes and prognostic factors in Japanese patients with recurrent or metastatic squamous cell carcinoma of head and neck treated with chemotherapy plus cetuximab: a prospective observation study (JROSG12-2). Int J Clin Oncol 26, 316–325 (2021). https://doi.org/10.1007/s10147-020-01817-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10147-020-01817-4

Keywords

Search

Navigation