Ricard Mesía1, Michael Henke2, Andre Fortin3, Heikki Minn4, Alejandro Cesar Yunes Ancona5, Anthony Cmelak6, Avi B Markowitz7, Sebastien J Hotte8, Simron Singh9, Anthony T C Chan10, Marco C Merlano11, Krzysztof Skladowski12, Alicia Zhang13, Kelly S Oliner13, Ari VanderWalde13, Jordi Giralt14. 1. Institut Catala d'Oncologia (ICO)-L'Hospitalet, Barcelona, Spain. Electronic address: rmesia@iconcologia.net. 2. Strahlenheilkunde Universitätsklinikum, Freiburg, Germany. 3. Centre Hospitalier Universitaire de Quebec-Hotel-Dieu de Quebec, Quebec, QC, Canada. 4. Turku University Hospital Department of Oncology and Radiotherapy, Turku, Finland. 5. Unidad de Oncología Servicios de Salud del Estado de Puebla, Puebla, Mexico. 6. Vanderbilt University Medical Center, Nashville, TN, USA. 7. University of Texas, Medical Branch, Galveston, TX, USA. 8. Juravinski Cancer Centre, Hamilton, ON, Canada. 9. Sunnybrook Health Sciences Centre-Odette Cancer Centre, Toronto, ON, Canada. 10. State Key Laboratory in Oncology in South China, The Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China. 11. Oncologia Medica ASOS Croce E Carle, Cuneo, Italy. 12. Centrum Onkologii Instytut M Sklodowskiej-Curie, Gliwice, Poland. 13. Amgen, Thousand Oaks, CA, USA. 14. Hospital Vall d'Hebron, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra, Spain.
Abstract
BACKGROUND:Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independentvendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. FINDINGS:Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in thepanitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. INTERPRETATION: In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. FUNDING: Amgen.
RCT Entities:
BACKGROUND:Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥ 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760. FINDINGS: Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemoradiotherapy group. INTERPRETATION: In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed. FUNDING: Amgen.
Authors: Min Yao; Charles Woods; Pierre Lavertu; Pingfu Fu; Michael Gibson; Rod Rezaee; Chad Zender; Jay Wasman; Neelesh Sharma; Mitchell Machtay; Panayiotis Savvides Journal: Head Neck Date: 2016-02-26 Impact factor: 3.147
Authors: J Martínez-Trufero; A Lozano Borbalas; I Pajares Bernad; M Taberna Sanz; E Ortega Izquierdo; B Cirauqui Cirauqui; J Rubió-Casadevall; M Plana Serrahima; J M Ponce Ortega; I Planas Toledano; J Caballero; J Marruecos Querol; L Iglesias Docampo; J Lambea Sorrosal; J C Adansa; R Mesía Nin Journal: Clin Transl Oncol Date: 2021-04-19 Impact factor: 3.405