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Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials

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Abstract

Background

The present meta-analysis was updated with randomized controlled trials (RCTs) to revaluate the efficacy and safety of cetuximab vs. cisplatin combined with radiotherapy in patients of head and neck squamous cell carcinoma (HNSCC).

Methods

A meta-analysis containing RCTs that compared the efficacy or toxicity of cetuximab and cisplatin in HNSCC patients was conducted.

Results

Seven RCTs were included in the final analysis. The patients treated by cetuximab plus radiotherapy showed an inferior overall survival (OS) and locoregional control (LRC) compared to cisplatin plus radiotherapy. The tendency of progression-free survival (PFS) was in agreement with OS and LRC. Subgroup analysis showed that cetuximab had poorer OS relative to cisplatin in the absence of induction chemotherapy. The profile of severe adverse events (SAEs) varied between the two groups, no significant difference in total SAEs was shown for the two arms.

Discussion

Cetuximab combined with radiotherapy shows significantly reduced therapeutic efficacy compared to cisplatin plus radiotherapy in HNSCC patients.

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Availability of data and materials

All datasets generated for this study are included in the article.

References

  1. Siegel RL, Miller KD, Jemal A (2019) Cancer statistics, 2019. CA Cancer J Clin 69(1):7–34

    Article  Google Scholar 

  2. Marur S, Forastiere AA (2016) Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc 91(3):386–396

    Article  Google Scholar 

  3. Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, Kim H, Silverman C, Raben A, Galloway TJ et al (2014) Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology Group 0129 trial: long-term report of efficacy and toxicity. J Clin Oncol 32(34):3858–3866

    Article  CAS  Google Scholar 

  4. Al-Sarraf M, LeBlanc M, Giri PG, Fu KK, Cooper J, Vuong T, Forastiere AA, Adams G, Sakr WA, Schuller DE et al (1998) Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16(4):1310–1317

    Article  CAS  Google Scholar 

  5. Jonker DJ, O’Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ et al (2007) Cetuximab for the treatment of colorectal cancer. N Engl J Med 357(20):2040–2048

    Article  CAS  Google Scholar 

  6. Chan JA, Blaszkowsky LS, Enzinger PC, Ryan DP, Abrams TA, Zhu AX, Temel JS, Schrag D, Bhargava P, Meyerhardt JA et al (2011) A multicenter phase II trial of single-agent cetuximab in advanced esophageal and gastric adenocarcinoma. Ann Oncol 22(6):1367–1373

    Article  CAS  Google Scholar 

  7. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D et al (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359(11):1116–1127

    Article  CAS  Google Scholar 

  8. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354(6):567–578

    Article  CAS  Google Scholar 

  9. Argiris A, Karamouzis MV, Raben D, Ferris RL (2008) Head and neck cancer. Lancet 371(9625):1695–1709

    Article  CAS  Google Scholar 

  10. Caudell JJ, Sawrie SM, Spencer SA, Desmond RA, Carroll WR, Peters GE, Nabell LM, Meredith RF, Bonner JA (2008) Locoregionally advanced head and neck cancer treated with primary radiotherapy: a comparison of the addition of cetuximab or chemotherapy and the impact of protocol treatment. Int J Radiat Oncol Biol Phys 71(3):676–681

    Article  CAS  Google Scholar 

  11. Magrini SM, Buglione M, Corvo R, Pirtoli L, Paiar F, Ponticelli P, Petrucci A, Bacigalupo A, Crociani M, Lastrucci L et al (2016) Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a randomized phase II trial. J Clin Oncol 34(5):427–435

    Article  CAS  Google Scholar 

  12. Levy A, Blanchard P, Bellefqih S, Brahimi N, Guigay J, Janot F, Temam S, Bourhis J, Deutsch E, Daly-Schveitzer N et al (2014) Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas. Strahlenther Onkol 190(9):823–831

    Article  Google Scholar 

  13. Tang C, Chan C, Jiang W, Murphy JD, von Eyben R, Colevas AD, Pinto H, Lee-Enriquez N, Kong C, Le QT (2015) Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer. Head Neck 37(3):386–392

    Article  Google Scholar 

  14. Huang J, Zhang J, Shi C, Liu L, Wei Y (2016) Survival, recurrence and toxicity of HNSCC in comparison of a radiotherapy combination with cisplatin versus cetuximab: a meta-analysis. BMC Cancer 16:689

    Article  Google Scholar 

  15. Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ, Jordan RCK, Zhao W, Sturgis EM, Burtness B et al (2019) Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet 393(10166):40–50

    Article  CAS  Google Scholar 

  16. Hitt R, Mesia R, Grau JJ, Iglesias L, Barco ED, Lozano A, Trufero JM, Giron CG, Martin AL, Hernandez JJC (2016) Randomized phase III trial of induction chemotherapy (ICT) with docetaxel-cisplatin-5fluorouracil (DCF) followed by cisplatin-radiotherapy (CRT) or cetuximab-radiotherapy (CetRT) in patients (pts) with locally advanced unresectable head and neck cancer (LAUHNC). 34(15_suppl):6001

  17. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T, Dalby M, Mistry P, Sen M, O’Toole L et al (2019) Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393(10166):51–60

    Article  CAS  Google Scholar 

  18. Gebre-Medhin M, Brun E, Engstrom P, Haugen Cange H, Hammarstedt-Nordenvall L, Reizenstein J, Nyman J, Abel E, Friesland S, Sjodin H et al (2021) ARTSCAN III: a randomized phase III study comparing chemoradiotherapy with cisplatin versus cetuximab in patients with locoregionally advanced head and neck squamous cell cancer. J Clin Oncol 39(1):38–47.

  19. Janoray G, Pointreau Y, Alfonsi M, Sire C, Geoffrois L, de Raucourt D, Bardet E, Calais MH, Garaud P, Calais G (2020) Induction chemotherapy followed by cisplatin or cetuximab concomitant to radiotherapy for laryngeal/hypopharyngeal cancer: long-term results of the TREMPLIN randomised GORTEC trial. Eur J Cancer (Oxford, England: 1990). 133:86–93

    Article  CAS  Google Scholar 

  20. Maddalo M, Borghetti P, Tomasini D, Corvo R, Bonomo P, Petrucci A, Paiar F, Lastrucci L, Bonu ML, Greco D et al (2020) Cetuximab and radiation therapy versus cisplatin and radiation therapy for locally advanced head and neck cancer: long-term survival and toxicity outcomes of a randomized phase 2 trial. Int J Radiat Oncol Biol Phys 107(3):469–477

  21. Lefebvre JL, Pointreau Y, Rolland F, Alfonsi M, Baudoux A, Sire C, de Raucourt D, Malard O, Degardin M, Tuchais C et al (2013) Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol 31(7):853–859

    Article  CAS  Google Scholar 

  22. Suton P, Skelin M, Rakusic Z, Dokuzovic S, Luksic I (2019) Cisplatin-based chemoradiotherapy vs. cetuximab-based bioradiotherapy for p16-positive oropharyngeal cancer: an updated meta-analysis including trials RTOG 1016 and De-ESCALaTE. Eur Arch Otorhinolaryngol 276(5):1275–1281

    Article  Google Scholar 

  23. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tan PF, Westra WH, Chung CH, Jordan RC, Lu C et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24–35

    Article  CAS  Google Scholar 

  24. Richards L (2010) Human papillomavirus-a powerful predictor of survival in patients with oropharyngeal cancer. Nat Rev Clin Oncol 7(9):481

    Article  Google Scholar 

  25. Moher D, Liberati A, Tetzlaff J, Altman DG, Grp P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Plos Med 6(7):e1000097

  26. Furlan AD, Pennick V, Bombardier C, van Tulder M, Editorial Board CBRG (2009) 2009 updated method guidelines for systematic reviews in the Cochrane Back Review Group. Spine (Phila Pa 1976) 34(18):1929–1941

    Article  Google Scholar 

  27. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials 17(1):1–12

    Article  CAS  Google Scholar 

  28. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–2834

    Article  CAS  Google Scholar 

  29. Ghi MG, Paccagnella A, Ferrari D, Foa P, Alterio D, Codeca C, Nole F, Verri E, Orecchia R, Morelli F et al (2017) Induction TPF followed by concomitant treatment versus concomitant treatment alone in locally advanced head and neck cancer. A phase II-III trial. Ann Oncol 28(9):2206–2212

    Article  CAS  Google Scholar 

  30. Taberna M, Oliva M, Mesia R (2019) Cetuximab-containing combinations in locally advanced and recurrent or metastatic head and neck squamous cell carcinoma. Front Oncol 9:383

    Article  Google Scholar 

  31. Riaz N, Sherman E, Koutcher L, Shapiro L, Katabi N, Zhang Z, Shi W, Fury M, Wong R, Wolden S et al (2016) Concurrent chemoradiotherapy with cisplatin versus cetuximab for squamous cell carcinoma of the head and neck. Am J Clin Oncol 39(1):27–31

    Article  CAS  Google Scholar 

  32. Ley J, Mehan P, Wildes TM, Thorstad W, Gay HA, Michel L, Nussenbaum B, Trinkaus K, Adkins D (2013) Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Oncology 85(5):290–296

    Article  CAS  Google Scholar 

  33. Hu MH, Wang LW, Lu HJ, Chu PY, Tai SK, Lee TL, Chen MH, Yang MH, Chang PM (2014) Cisplatin-based chemotherapy versus cetuximab in concurrent chemoradiotherapy for locally advanced head and neck cancer treatment. Biomed Res Int 2014:904341

    Article  Google Scholar 

  34. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu 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. Lancet Oncol 11(1):21–28

    Article  CAS  Google Scholar 

  35. Rosenthal DI, Harari PM, Giralt J, Bell D, Raben D, Liu J, Schulten J, Ang KK, Bonner JA (2016) Association of human papillomavirus and p16 status with outcomes in the IMCL-9815 phase III registration trial for patients with locoregionally advanced oropharyngeal squamous cell carcinoma of the head and neck treated with radiotherapy with or without cetuximab. J Clin Oncol 34(12):1300–1308

    Article  CAS  Google Scholar 

  36. Beckham TH, Barney C, Healy E, Wolfe AR, Branstetter A, Yaney A, Riaz N, McBride SM, Tsai CJ, Kang J et al (2020) Platinum-based regimens versus cetuximab in definitive chemoradiation for human papillomavirus-unrelated head and neck cancer. Int J Cancer 147(1):107–115

    Article  CAS  Google Scholar 

  37. Safran H, Suntharalingam M, Dipetrillo T, Ng T, Doyle LA, Krasna M, Plette A, Evans D, Wanebo H, Akerman P et al (2008) Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity. Int J Radiat Oncol Biol Phys 70(2):391–395

    Article  CAS  Google Scholar 

  38. Pryor DI, Porceddu SV, Burmeister BH, Guminski A, Thomson DB, Shepherdson K, Poulsen M (2009) Enhanced toxicity with concurrent cetuximab and radiotherapy in head and neck cancer. Radiother Oncol 90(2):172–176

    Article  CAS  Google Scholar 

  39. Bar-Ad V, Zhang QE, Harari PM, Axelrod R, Rosenthal DI, Trotti A, Jones CU, Garden AS, Song G, Foote RL et al (2016) Correlation between the severity of cetuximab-induced skin rash and clinical outcome for head and neck cancer patients: the RTOG experience. Int J Radiat Oncol Biol Phys 95(5):1346–1354

    Article  Google Scholar 

  40. Weycker D, Li X, Tzivelekis S, Atwood M, Garcia J, Li Y, Reiner M, Lyman GH (2017) Burden of chemotherapy-induced febrile neutropenia hospitalizations in US clinical practice, by use and patterns of prophylaxis with colony-stimulating factor. Supportive Care Cancer 25(2):439–447

    Article  Google Scholar 

  41. Sheth S, Mukherjea D, Rybak LP, Ramkumar V (2017) Mechanisms of Cisplatin-Induced Ototoxicity and Otoprotection. Front Cell Neurosci 11:338

    Article  Google Scholar 

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Acknowledgements

We would like to thank Bashir Kaspo (University of Michigan) for his guidance on the language of this article.

Funding

This study was partially supported by the National Natural Science Foundation of China (no. 81202962).

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Authors and Affiliations

  1. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 156 Wujiadun, Jianghan District, Wuhan, 430022, Hubei, China

    Yuting Li, Chensu Yang & You Qin

  2. School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yong Gan

  3. Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Furong Lu

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Contributions

Study conception and design, data interpretation, and manuscript writing and reviewing: YL, YQ, and FL. Literature review: YL and CY. Data extraction: CY and YQ. Statistical analysis: YG and YL.

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Correspondence to You Qin.

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SupplementaryFig. 1 Meta-analysis results of 3-year LRC without induction chemotherapy.

*The long-term results of Lefebvre’s studyreported by Janoray et al. in 2020 were also included in the final analysis (PDF 504 KB)

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Li, Y., Yang, C., Gan, Y. et al. Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. Eur Arch Otorhinolaryngol 280, 11–22 (2023). https://doi.org/10.1007/s00405-022-07572-8

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