Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1)

A randomised, controlled, open-label phase 2 trial

Ricard Mesía, Michael Henke, Andre Fortin, Heikki Minn, Alejandro Cesar Yunes Ancona, Anthony Cmelak, Avi B. Markowitz, Sebastien J. Hotte, Simron Singh, Anthony T.C. Chan, Marco C. Merlano, Krzysztof Skladowski, Alicia Zhang, Kelly S. Oliner, Vanderwalde Ari, Jordi Giralt

Research output: Contribution to journalArticle

72 Citations (Scopus)

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 independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m2) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m2) 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.

Original languageEnglish (US)
Pages (from-to)208-220
Number of pages13
JournalThe Lancet Oncology
Volume16
Issue number2
DOIs
StatePublished - Feb 1 2015

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Chemoradiotherapy
Cisplatin
Carcinoma, squamous cell of head and neck
panitumumab
Radiation Injuries
Deglutition Disorders
Clinical Protocols
Random Allocation
Radiotherapy
Monoclonal Antibodies
Radiation
Inflammation

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1) : A randomised, controlled, open-label phase 2 trial. / Mesía, Ricard; Henke, Michael; Fortin, Andre; Minn, Heikki; Yunes Ancona, Alejandro Cesar; Cmelak, Anthony; Markowitz, Avi B.; Hotte, Sebastien J.; Singh, Simron; Chan, Anthony T.C.; Merlano, Marco C.; Skladowski, Krzysztof; Zhang, Alicia; Oliner, Kelly S.; Ari, Vanderwalde; Giralt, Jordi.

In: The Lancet Oncology, Vol. 16, No. 2, 01.02.2015, p. 208-220.

Research output: Contribution to journalArticle

Mesía, R, Henke, M, Fortin, A, Minn, H, Yunes Ancona, AC, Cmelak, A, Markowitz, AB, Hotte, SJ, Singh, S, Chan, ATC, Merlano, MC, Skladowski, K, Zhang, A, Oliner, KS, Ari, V & Giralt, J 2015, 'Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): A randomised, controlled, open-label phase 2 trial', The Lancet Oncology, vol. 16, no. 2, pp. 208-220. https://doi.org/10.1016/S1470-2045(14)71198-2
Mesía, Ricard ; Henke, Michael ; Fortin, Andre ; Minn, Heikki ; Yunes Ancona, Alejandro Cesar ; Cmelak, Anthony ; Markowitz, Avi B. ; Hotte, Sebastien J. ; Singh, Simron ; Chan, Anthony T.C. ; Merlano, Marco C. ; Skladowski, Krzysztof ; Zhang, Alicia ; Oliner, Kelly S. ; Ari, Vanderwalde ; Giralt, Jordi. / Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1) : A randomised, controlled, open-label phase 2 trial. In: The Lancet Oncology. 2015 ; Vol. 16, No. 2. pp. 208-220.
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T1 - Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1)

T2 - A randomised, controlled, open-label phase 2 trial

AU - Mesía, Ricard

AU - Henke, Michael

AU - Fortin, Andre

AU - Minn, Heikki

AU - Yunes Ancona, Alejandro Cesar

AU - Cmelak, Anthony

AU - Markowitz, Avi B.

AU - Hotte, Sebastien J.

AU - Singh, Simron

AU - Chan, Anthony T.C.

AU - Merlano, Marco C.

AU - Skladowski, Krzysztof

AU - Zhang, Alicia

AU - Oliner, Kelly S.

AU - Ari, Vanderwalde

AU - Giralt, Jordi

PY - 2015/2/1

Y1 - 2015/2/1

N2 - 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/m2) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m2) 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.

AB - 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/m2) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m2) 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.

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