Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Survival, recurrence and toxicity of HNSCC in comparison of a radiotherapy combination with cisplatin versus cetuximab: a meta-analysis

Authors: Jingwen Huang, Jing Zhang, Changle Shi, Lei Liu, Yuquan Wei

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

Cisplatin-based treatment has been considered the standard treatment regimen of HNSCC. Cetuximab is an emerging target therapy that has potential therapeutic benefits over cisplatin. Nevertheless, curative effects of cisplatin-based chemoradiotherapy (CRT) versus cetuximab-based bioradiotherapy (BRT) are still controversial.

Methods

Potentially eligible studies were retrieved using PubMed, Embase and Medline. Basic characteristics of patients and statistical data were collected. A meta-analysis model was established to compare CRT and BRT.

Results

Thirty-one eligible studies and 4212 patients were found. The pooled HRs with 95 % confidence intervals (CIs) for OS and PFS were 0.32 [0.09, 0.55] and 0.51 [0.22, 0.80], respectively, and both were in favor of cisplatin. However, 3-year survival and recurrence analysis of the subgroups showed no differences between the two groups (p > 0.05). In subgroup analysis, oropharyngeal primary tumors exhibited improved results by cetuximab with a pooled HR of 1.56 [1.14, 2.13] for PFS. Additionally, the HPV+ status was a significant factor in positive outcomes with cetuximab with a pooled HR of 1.12 [0.46, 2.17] for OS.

Conclusion

Long-term use of BRT showed no significant difference compared with CRT, and both arms showed different aspects of toxicity. In subgroup analysis, taking the effects of treatment and adverse events into consideration, cetuximab plus radiation may show superior responses regarding OS and PFS in patients who have HPV+ or primary oropharyngeal HNSCC, respectively, but physicians should administer them with caution.
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMed
2.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.CrossRefPubMed
3.
Bar-Ad V, Palmer J, Yang H, Cognetti D, Curry J. Current management of locally advanced head and neck cancer: the combination of chemotherapy with locoregional treatments. Semin Oncol. 2014;41(6):798–806.CrossRefPubMed
4.
Pignon JP, le Maitre A, Maillard E, et al. MACH-NC Collaborative Group: meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomized trials and 17,346 patients. Radiother Oncol. 2009;92:4–14.CrossRefPubMed
5.
Cooper JS, PAJAK TF, Forestiere AA, et al. Postoperative irradiation with or without concomitant chemotherapy for high-risk squamous cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937–44.CrossRefPubMed
6.
Rubin GJ, Chakraborty A, Melhem MF, Zeng Q, Tweardy DJ. Inhibition of epidermal growth factor receptor gene expression and function decreases proliferation of head and neck squamous carcinoma but not normal mucosal epithelial cells. Oncogene. 1997;15(4):409–16.CrossRef
7.
Kalyankrishna S, Grandis JR. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006;24(17):2666–72.CrossRefPubMed
8.
Ozanne B, Richards CS, Hendler F, Burns D, Gusterson B. Over-expression of the EGF receptor is a hallmark of squamous cell carcinomas. J Pathol. 1986;149(1):9–14.CrossRefPubMed
9.
Ma X, Huang J, Wu X, et al. Epidermal growth factor receptor could play a prognostic role to predict the outcome of nasopharyngeal carcinoma: a meta-analysis. Cancer Biomark. 2014;14(4):267–77.PubMed
10.
Keedy VL, Temin S, Somerfield MR, et al. American society of clinical oncology provisional clinical opinion: epidermal growth factor receptor (EGFR) Mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol. 2011;29(15):2121–7.CrossRefPubMed
11.
Sequist LV, von PJ, Garmey EG, et al. Randomized phase II study of erlotinib plus tivantinib versus erlotinib plus placebo in previously treated non-small-cell lung cancer. J Clin Oncol. 2011;29(24):3307–15.CrossRefPubMed
12.
Shah MA, Jhawer M, Ilson DH, et al. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011;29(7):868–74.CrossRefPubMed
13.
Mehra R, Cohen RB, Burtness BA.The role of cetuximab for the treatment of squamous cell carcinoma of the head and neck. Clin Adv Hematol Oncol. 2008;6(10):742–50
14.
Kono SA, Haigentz Jr M, Yom SS, Saba N. EGFR Monoclonal antibodies in the treatment of squamous cell carcinoma of the head and neck: a view beyond cetuximab. Chemother Res Pract. 2012;2012:901320.PubMedPubMedCentral
15.
Cohen MH, Chen H, Shord S, et al. Approval summary: Cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Oncologist. 2013;18(4):460–6.CrossRefPubMedPubMedCentral
16.
Bonner JA, Harari PM, Giralt J, 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. Lancet Oncol. 2010;11(1):21–8.CrossRefPubMed
17.
Merlano M, Russi E, Benasso M, Corvò R, Colantonio I, et al. Cisplatin-based chemoradiation plus cetuximab in locally advanced head and neck cancer: a phase II clinical study. Ann Oncol. 2007;22(3):712–7.CrossRef
18.
Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32(27):2940–50.CrossRefPubMedPubMedCentral
19.
Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. 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. 2005;23(34):8646–54.CrossRefPubMed
20.
JPT Higgins SG. Cochrane handbook for systematic reviews of interventions. The Cochrane Library. 2005
21.
Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med. 1998;17(24):2815–34.CrossRefPubMed
22.
Williamson PR, Smith CT, Hutton JL, Marson AG. Aggregate data meta-analysis with time-to-event outcomes. Stat Med. 2002;21(22):3337–51.CrossRefPubMed
23.
Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16.CrossRefPubMedPubMedCentral
24.
25.
Walsh L, et al. Toxicity of cetuximab versus cisplatin concurrent with radiotherapy in locally advanced head and neck squamous cell cancer (LAHNSCC). Radiother Oncol. 2011;98(1):38–41.CrossRefPubMed
26.
Caudell JJ, Sawrie SM, Spencer SA, et al. 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. 2008;71(3):676–81.CrossRefPubMed
27.
L. D. Koutcher ES, D. Carlson NK, M. Fury SW, Z. Zhang QM, D. Pfister. Cisplatin (CDDP) and Radiation (RT) versus Cetuximab (C) and RT in the Context ofHuman Papillomavirus (HPV) and P16 in the Treatment of Locally Advanced Head and Neck Cancer (LAHNC). 2012. Annual ASTRO Meeting.
28.
Jensen AD, Krauss J, Weichert W, et al. Disease control and functional outcome in three modern combined organ preserving regimens for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Radiat Oncol. 2011;6:122.CrossRefPubMedPubMedCentral
29.
Koutcher L, Sherman E, Fury M, et al. Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):915–22.CrossRefPubMed
30.
Beijer YJ, Koopman M, Terhaard CH, Braunius WW, van Es RJ, de Graeff A. Outcome and toxicity of radiotherapy combined with chemotherapy or cetuximab for head and neck cancer: our experience in one hundred and twenty-five patients. Clin Otolaryngol. 2013;38(1):69–74.CrossRefPubMed
31.
Ley J, Mehan P, Wildes TM, et al. Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. Oncology. 2013;85(5):290–6.CrossRefPubMedPubMedCentral
32.
Ye AY, Hay JH, Laskin JJ, Wu JS, Ho CC. Toxicity and outcomes in combined modality treatment of head and neck squamous cell carcinoma: cisplatin versus cetuximab. J Cancer Res Ther. 2013;9(4):607–12.CrossRefPubMed
33.
Pajares B, Trigo JM, Toledo MD, et al. 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. 2013;13:26.CrossRefPubMedPubMedCentral
34.
Lefebvre JL, Pointreau Y, Rolland F, et al. Induction chemotherapy followed by either chemoradiotherapy or bioradiotherapy for larynx preservation: the TREMPLIN randomized phase II study. J Clin Oncol. 2013;31(7):853–9.CrossRefPubMed
35.
M. Ghi AP, R. Orecchia SP, F. Bertoni NM. A Phase 2-3 Study Comparing Concomitant Chemoradiation Therapy (CRT) Versus Cetuximab/RT (CET/RT) With or Without Induction Docetaxel/Cisplatin/5-Fluorouracil (TPF) in Locally-Advanced Head and Neck Squamous Cell Carcinoma (LASCCHN) e Efficacy Results of the GSTTC Italian Study (NCT01086826). Int J Radiat Oncol Biol Phys. 2013 [eAbstract] .
36.
N. Riaz AB, D. Adkins SR, J. Huang PC, J. Ley DK, W. Thorstad NL. 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 2008 [eAbstract].
37.
Hu MH, Wang LW, Lu HJ, et al. Cisplatin-based chemotherapy versus cetuximab in concurrent chemoradiotherapy for locally advanced head and neck cancer treatment. Biomed Res Int. 2014;2014:904341.PubMedPubMedCentral
38.
Levy A, Blanchard P, Bellefqih S, et al. Concurrent use of cisplatin or cetuximab with definitive radiotherapy for locally advanced head and neck squamous cell carcinomas. Strahlenther Onkol. 2014;190(9):823–31.CrossRefPubMed
39.
Tang C, Chan C, Jiang W, et al. Concurrent cetuximab versus platinum-based chemoradiation for the definitive treatment of locoregionally advanced head and neck cancer. Head Neck. 2015;37(3):386–92.CrossRefPubMed
40.
Fayette J, Bonnin N, Ferlay C, et al. Neoadjuvant TPF in locally advanced head and neck cancer can be followed by radiotherapy combined with cisplatin or cetuximab: a study of 157 patients. Anticancer Drugs. 2013;24(6):623–9.PubMed
41.
Huang J, Baschnagel AM, Chen P, et al. A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer. Int J Clin Oncol. 2014;19(2):240–6.CrossRefPubMed
42.
Shapiro LQ, Sherman EJ, Riaz N, et al. Efficacy of concurrent cetuximab vs. 5-fluorouracil/carboplatin or high-dose cisplatin with intensity-modulated radiation therapy (IMRT) for locally-advanced head and neck cancer (LAHNSCC). Oral Oncol. 2014;50(10):947–55.CrossRefPubMed
43.
Kanakamedala MR SPG, Abraham RS AAA, Vijayakumar S aRDH. Comparison of Cisplatin Versus Cetuximab With Intensity Modulated Radiation Therapy in Locally Advanced Squamous Cell Carcinomas of Head and Neck: Toxicity, Patterns of Failure, and Survival Analysis. Radiat Oncol. 2014;90(15). Annual ASTRO Meeting.
44.
N. Riaz AB, D. Adkins SR, J. Huang PC, J. Ley DK, W. Thorstad NL. Multi-institution Analysis of Concurrent Chemoradiation Therapy With Cisplatin (CDDP) Versus Cetuximab (C225) in Locally Advanced Squamous Cell Carcinoma of the Head and Neck (LAHNSCC): Can HPV Help Decide Which Agent. Int J Radiat Oncol Supplement 2014 [eAbstract].
45.
Peddi P, Shi R, Nair B, Ampil F, Mills GM, Jafri SH. Cisplatin, cetuximab, and radiation in locally advanced head and neck squamous cell cancer: a retrospective review. Clin Med Insights Oncol. 2015;9:1–7.CrossRefPubMedPubMedCentral
46.
S. L. Galper HD, Decker MGRaRH. Cetuximab versus cisplatin concurrent with IMRT in locally advanced head and neck cancer (LAHNC). J Clin Oncol ASCO Annual Meeting. 2009. 27(e17030).
47.
Delphine Borchiellini CD, Jocelyn Gal BL, Marc Alfonsi KB, Christian Righini BG, Beltran M. Induction TPF followed by chemoradiation or radiotherapy-cetuximab in nonresectable advanced head and neck squamous cell carcinoma: A retrospective study in 164 patients . Int J Radiat Oncol. 2012;30(e16044).
48.
Strom TJ, et al. Comparison of every 3 week cisplatin or weekly cetuximab with concurrent radiotherapy for locally advanced head and neck cancer. Oral Oncol. 2015;51(7):704–8.CrossRefPubMed
49.
Riaz N, et al. Concurrent chemoradiotherapy with cisplatin versus cetuximab for squamous cell carcinoma of the head and neck. Am J Clin Oncol. 2016;39(1):27–31.CrossRefPubMedPubMedCentral
50.
Magrini SM, et al. Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a randomized phase II trial. J Clin Oncol. 2016;34(5):427–35.CrossRefPubMed
51.
Network NCC. NCCN head and neck cancers guidelines (Version 1, 2016). America: NCCN; 2016.
52.
Robert F, Ezekiel MP, Spencer SA, Meredith RF, et al. Phase I study of anti-epidermal growth factor receptor antibody cetuximab in combination with radiationtherapy in patients with advanced head and neck cancer. J Clin Oncol. 2001;19(13):3234–43.PubMed
53.
Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567–78.CrossRefPubMed
54.
Petrelli F, Coinu A, Riboldi V, et al. 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. 2014;50(11):1041–8.CrossRefPubMed
55.
Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–9.CrossRefPubMed
56.
Gillison ML, Harris J, Westra W, et al. Survival outcomes bytumor human papillomavirus (HPV) in stage III-IV oropharyngeal cancer (OPC) in RTOG 0129 [Abstract]. Proc Am SocClinOncol 2009;27(Suppl.):15 s .
57.
Dayyani F, Etzel CJ, Liu M, Ho CH, Lippman SM, Tsao AS. Meta-analysis of the impact of human papillomavirus (HPV) on cancer risk and overall survival in head and neck squamous cell carcinomas (HNSCC). Head Neck Oncol. 2010;2:15.CrossRefPubMed
58.
Riaz N, Sherman E, Koutcher L, et al. Concurrent chemoradiotherapy with cisplatin versus cetuximab for squamous cell carcinoma of the head and neck. Am J Clin Oncol. 2014.
59.
Blanchard P, Baujat B, Holostenco V, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100(1):33–40.CrossRefPubMed
60.
Lill C, Kornek G, Bachtiary B, Selzer E, et al. Survival of patients with HPV-positive oropharyngeal cancer after radiochemotherapy is significantly enhanced.Wien Klin Wochenschr. 2011;123(7–8):215–21.
61.
Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev. 2005;14(2):467–75.CrossRefPubMed
62.
Termine N, Panzarella V, Falaschini S, et al. HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma biopsies: a meta-analysis (1988-2007). Ann Oncol. 2008;19(10):1681–90.CrossRefPubMed
63.
Koutcher LD, Wolden S, Lee N. Severe radiation dermatitis in patients with locally advanced head and neck cancer treated with concurrent radiation and cetuximab. Am J Clin Oncol. 2009;32(5):472–6.CrossRefPubMed
64.
Elliott EA, et al. Phase III Trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99-13. J Clin Oncol. 2006;24(13):2092–7.CrossRefPubMed
65.
Dorr W, Hendry JH. Consequential late effects in normal tissues. Radiother Oncol. 2001;61(3):223–31.CrossRefPubMed
Metadata
Title
Survival, recurrence and toxicity of HNSCC in comparison of a radiotherapy combination with cisplatin versus cetuximab: a meta-analysis
Authors
Jingwen Huang
Jing Zhang
Changle Shi
Lei Liu
Yuquan Wei
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2706-2

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue

Debate

TAS-102, the first “cardio-gentle” fluoropyrimidine in the colorectal cancer landscape?

Study protocol

Assessment of laparoscopic stomach preserving surgery with sentinel basin dissection versus standard gastrectomy with lymphadenectomy in early gastric cancer–A multicenter randomized phase III clinical trial (SENORITA trial) protocol

Technical advance

Efficient generation of patient-matched malignant and normal primary cell cultures from clear cell renal cell carcinoma patients: clinically relevant models for research and personalized medicine

Study protocol

Web-based stress management for newly diagnosed cancer patients (STREAM-1): a randomized, wait-list controlled intervention study

Research article

miRNA profiling, detection of BRAF V600E mutation and RET-PTC1 translocation in patients from Novosibirsk oblast (Russia) with different types of thyroid tumors

Research article

Variation in use of targeted therapies for metastatic renal cell carcinoma: Results from a Dutch population-based registry
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits