Human papilloma virus (HPV)-associated oropharyngeal cancer (OPC) is a special entity among head and neck squamous cell carcinomas (HNSCCs). Given its favorable prognosis, one of the de-escalating strategies in the treatment of OPC includes the introduction of cetuximab (C225) instead of cisplatin (CDDP) in conjunction with radiotherapy. An updated meta-analysis of published studies has been performed, which directly compared the efficacy of CDDP vs. C225 given concurrently with radiotherapy as definitive treatment of p16-positive OPC.
A systematic literature search was performed for studies published between 2006 and 2018. A total of 1490 citations were obtained and 8 studies met inclusion criteria, with a total of 1665 patients.
The data from seven studies were available for the analysis of 2-year overall survival (OS). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy, was 0.45 (P < 0.0001). The data from eight studies were available for the analysis of 2-year locoregional recurrence (LRR). Calculated pooled OR for CDDP-based chemoradiotherapy vs. C225-based bioradiotherapy was 0.35 (P < 0.0001). Patients receiving CDDP with irradiation had 2.2- and 2.9-fold decreased risk for death from any cause and LRR, respectively.
For patients with HPV-positive OPC, radiotherapy plus C225 showed inferior OS and higher LRR rates compared with radiotherapy plus CDDP. CDDP-based chemoradiotherapy should remain standard of definitive treatment of p16-positive OPC.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price excludes VAT (USA)
Tax calculation will be finalised during checkout.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90
Fountzilas G, Ciuleanu E, Dafni U, Plataniotis G, Kalogera-Fountzila A, Samantas E et al (2004) Concomitant radiochemotherapy vs radiotherapy alone in patients with head and neck cancer: a hellenic cooperative oncology group phase III study. Med Oncol 21:95–107
Bourhis J, Sire C, Graff P, Grégoire V, Maingon P, Calais G et al (2012) Concomitant chemoradiotherapy versus acceleration of radiotherapy with or without concomitant chemotherapy in locally advanced head and neck carcinoma (GORTEC 99–02): an open-label phase 3 randomised trial. Lancet Oncol 13:145–153
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB et al (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK 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 11:21–28
Fakhry C, Westra WH, Li S, Cmelak A, Ridge JA, Pinto H et al (2008) Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst 100:261–269
Gillison ML, Trotti AM, Harris J, Eisbruch A, Harari PM, Adelstein DJ 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 393:40–50
Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T 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 393:51–60
Suton P, Skelin M, Luksic I. Concurrent cisplatin-based chemoradiotherapy versus cetuximab-based bioradiotherapy for p16-positive, locally advanced oropharyngeal cancer: A meta-analysis. Ann Oncol (2018) 29(suppl_8):viii372–viii399. https://doi.org/10.1093/annonc/mdy287
Guyot P, Ades AE, Ouwens MJ, Welton NJ (2012) Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol 12:9
Barney CL, Walston S, Zamora P, Healy EH, Nolan N, Diavolitsis VM et al (2018) Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma. Oral Oncol 79:9–14
Buglione M, Maddalo M, Corvò R, Pirtoli L, Paiar F, Lastrucci L et al (2017) Subgroup analysis according to human papillomavirus status and tumor site of a randomized Phase II trial comparing cetuximab and cisplatin combined with radiation therapy for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys 97:462–472
Pajares B, Trigo JM, Toledo MD, Álvarez M, González-Hermoso C, Rueda A et al (2013) Differential outcome of concurrent radiotherapy plus epidermal growth factor receptor inhibitors versus radiotherapy plus cisplatin in patients with human papillomavirus-related head and neck cancer. BMC Cancer 13:26
Riaz N, Baschnagel A, Adkins D, Rao S, Huang J, Chen P et al (2014) Multi-institution analysis of concurrent chemoradiation therapy with cisplatin (CDDP) versus cetuximab (C225) in locally advanced squamous cell carcinoma of the head and neck (LA-HNSCC): can HPV help decide which agent? Int J Radiat Oncol Biol Phys 88:472
Strom TJ, Trotti AM, Kish J, Russell JS, Rao NG, McCaffrey J et al (2015) Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer. Oral Oncol 51:704–708
Tang C, Chan C, Jiang W, Murphy JD, von Eyben R, Colevas AD et al (2015) Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer. Head Neck 37:386–392
Soo KC, Tan EH, Wee J, Lim D, Tai BC, Khoo ML et al (2005) Surgery and adjuvant radiotherapy vs concurrent chemoradiotherapy in stage III/IV nonmetastatic squamous cell head and neck cancer: a randomised comparison. Br J Cancer 93:279–286
Pignon JP, le Maître A, Maillard E, Bourhis J, MACH-NC Collaborative Group (2009) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 92:4–14
Ahn MJ, D’Cruz A, Vermorken JB (2016) Clinical recommendations for defining platinum unsuitable head and neck cancer patient populations on chemoradiotherapy: a literature review. Oral Oncol 53:10–16
Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26:3582–3589
National Comprehensive Cancer Network (NCCN). Head and Neck Cancer (Version 1, 2016). https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf
Caudell JJ, Sawrie SM, Spencer SA, Desmond RA, Carroll WR, Peters GE et al (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 71:676–681
Ley J, Mehan P, Wildes TM, Thorstad W, Gay HA, Michel L et al (2013) Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Oncology 85:290–296
Riaz N, Sherman EJ, Fury M, Lee N (2013) Should cetuximab replace cisplatin for definitive chemoradiotherapy in locally advanced head and neck cancer? J Clin Oncol 31:287–288
Petrelli F, Coinu A, Riboldi V, Borgonovo K, Ghilardi M, Cabiddu M et al (2014) Concomitant platinum-based chemotherapy or cetuximab with radiotherapy for locally advanced head and neck cancer: a systematic review and meta-analysis of published studies. Oral Oncol 50:1041–1048
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
Hong AM, Dobbins TA, Lee CS, Jones D, Harnett GB, Armstrong BK et al (2010) Human papillomavirus predicts outcome in oropharyngeal cancer in patients treated primarily with surgery or radiation therapy. Br J Cancer 103:1510–1517
Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363:24–35
Lindquist D, Romanitan M, Hammarstedt L, Näsman A, Dahlstrand H, Lindholm J et al (2007) Human papillomavirus is a favourable prognostic factor in tonsillar cancer ant itsoncogenic role is supported by the expression ofE6 and E7. Mol Oncol 1:350–355
Conflict of interest
We disclose any commercial associations that might pose a potential, perceived or real conflict of interest with the content of this article. These include grants, patent licensing arrangements, consultancies, stock or other equity ownership, donations, advisory board memberships, or payments for conducting or publicizing the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Suton, P., Skelin, M., Rakusic, Z. et al. 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, 1275–1281 (2019). https://doi.org/10.1007/s00405-019-05387-8
- Oropharyngeal cancer
- Human papilloma virus